PhD THESIS (Ozimo Gama, MD)
COMPARATIVE STUDY BETWEEN THE SLEEVE GASTRECTOMY AND GASTRIC PLICATION IN OBESE RATS
INTRODUCTION: Obesity results from a prolonged imbalance between energy intake and energy expenditure. Studies with experimental models of bariatric surgery provided a fundamental contribution to the understanding of morphological and functional changes in obesity and after bariatric surgery. The restrictive bariatric surgery techniques currently used are gastric banding, sleeve gastrectomy and the gastric plication. The latter is considered an experimental technique and has therefore not yet enough studies that shed light on the postoperative rates of weight loss, surgical complications, resolution of comorbidities and the mechanisms responsible for weight loss. The aim of this study was to conduct a comparative study in rats with cafeteria diet-induced, between gastric plication and sleeve gastrectomy in variation late postoperative in body weight ,plasma biochemistry and gross and microscopic alterations gastric effects obesity.
MATERIAL AND METHOD: 28 male Wistar rats were randomized into three groups after induction period of obesity by cafeteria diet and underwent sleeve gastrectomy (GV group), gastric plication (GP group) and sham operation (control group). The animals were assessed daily postoperatively and the variables were recorded: (initial seven days, 14 and 21 days) body weight and presence of complications until day 21 postoperatively, when they were euthanized and evaluated: biochemistry (glucose, insulin, HDL, total cholesterol, triglycerides, AST, ALT and serum ghrelin), degree of intra-abdominal adhesions, resistance testing will air insufflation in the stomach and microscopic evaluation of the gastric mucosa.
RESULTS: In relation to body weight variation of animals GV group (initial weight: 318 ± 7.89 g / Final weight: 213 ± 9.03g) was significantly decreased (p<0.05) at 21 post-surgery day compared to the GP group (initial weight: 314.11 ± 20.79 g / final weight: 239.16 ± 14.71 g) and control (initial weight: 315.16±17.54g / final weight: 317.91±16.06 g). The animals in the GV group had a significant decrease (p<0.001) in blood glucose, insulin, transaminases, serum HDL and ghrelin compared to animals in GP and control. Was also significantly lower the burst pressure of the stomach in the GV group, the insufflation test the atmospheric air in relation to the GP and control groups. The GP and GV groups showed even different histological grade of inflammation
(subacute inflammation) and control group (chronic inflammation).
CONCLUSIONS: The sleeve gastrectomy is more effective than gastric plication weight loss, metabolic control and reduction of serum ghrelin in obesity rats, and presents the same rates of postoperative complications (adhesions, deaths and grade inflammation).
KEYWORDS: 1. Obesity; 2. Bariatric Surgery; 3.Wistar rats.
Surgical Management of GERD After Sleeve Gastrectomy
Evaluation of a patient referring GERD after sleeve gastrectomy should start with a detailed history and physical examination; the presence or absence of GERD-related symptoms should be thoroughly documented as well as any prior treatments or therapy used to treat it. Obtaining preoperative and operative records is of paramount importance particularly in those patients who had their index procedure performed elsewhere. Any endoscopic findings and prior imaging available are important to determine what the best course of action would be. If the patient had preoperative and postoperative imaging such as UGI, it is useful to compare those with a recent study to look for anatomical problems that may have been not addressed at the time of the index operation or developed over time. After this information is obtained, we can classify the GERD after sleeve as:
1. De novo GERD
2. Preexisting GERD without improvement
3. Preexisting GERD with worsening/complication
Regardless of how we classify the GERD, an initial evaluation with imaging
studies such as UGI and EGD is recommended. Comparison with any prior films if available is of significant value. Based on the UGI, we can determine if the shape of the sleeve falls into one of the following categories: tubular, dilated bottom, dilated upper, or dumbbell-shaped sleeve; we will also be able to evaluate esophageal peristalsis in real time and if there is associated hiatal hernias. We believe UGI under fluoroscopy provides important physiologic and anatomic information that can help guide our management approach, and therefore we offer it to all patients. We follow the radiologic evaluation with endoscopy, and during endoscopy, we look for objective signs of reflux such as esophagitis, presence of bile in the stomach or esophagus, as well as missed or recurrent hiatal hernias. In patients with evidence of esophagitis or metaplasia, multiple biopsies are taken. During the endoscopy, subtle findings that suggest a kink or a stricture may be present. In the absence of objective signs of gastroesophageal reflux disease on both endoscopy and upper GI series, we pursue physiologic testing followed by highresolution manometry and pH monitoring. In those patients where clear reflux esophagitis is seen, this additional testing may not be necessary or may be performed in selected cases depending on what the surgical or endoscopic therapy would be.
While it is true that most sleeve-related GERD will be effectively treated with a conversion to Roux-en-Y gastric bypass, not every patient with GERD after reflux will require a bypass or would agree to have one. First key step in addressing the patient is to evaluate whether the patient was selected appropriately to have a sleeve and second is to determine the exact sleeve anatomy; are there anatomical factors that will make it more likely for this patient to experience reflux; is there dilated fundus? Is there a kink or stricture in the sleeve or is it an anatomically appropriate operation? We should pay important attention to the weight loss the patient has experienced with the sleeve. Patients who do not have adequate weight loss and have GERD symptoms should not undergo other therapies and should probably undergo a bypass; however it is our unpublished experience that patients with the association of poor weight loss after sleeve and difficult to treat GERD will correct their GERD after conversion, but their weight loss results are still marginal even with a well-constructed bypass.
Effects of Bariatric Surgery on Diabetes
Bariatric procedures differ in their ability to ameliorate T2DM, with intestinal bypass procedures generally associated with greater glycemic control and remission rates than purely restrictive procedures. There has been until now a paucity of data from RCTs comparing the efficacy of various bariatric procedures to treat diabetes. The recently published RCT by Schauer et al. also indicates superior efficacy of RYGB over sleeve gastrectomy in the treatment of diabetes in obese individuals. On the other hand, BPD produced greater remission of diabetes in morbidly obese patients compared to RYGB (95 % versus 75 %) in the RCT reported by Mingrone et al.
Sleeve Gastrectomy as Metabolic Surgery
Karamanakos et al. showed that LSG suppressed fasting and postprandial ghrelin levels and attributed this decrease in ghrelin to improved postoperative satiety and greater weight loss at 1year compared to LRYGB. The LRYGB group in this study had an initial decrease in ghrelin levels after surgery, but these levels returned to normal levels within 3 months. Lee et al. studied the treatment of patients with a low body mass index and type 2 diabetes mellitus between the two groups. LRYGB is reportedly more effective than LSG; they conclude that both procedures have strong hindgut effects after surgery, but LRYGB has a significant duodenal exclusion effect on cholecystokinin. The LSG group had lower acylated ghrelin and des-acylated ghrelin levels but greater concentrations of resistin than the LRYGB group. In addition to evaluations of ghrelin, there are now several small studies demonstrating that gastric emptying is increased after sleeve gastrectomy. The loss of a large reservoir in the gastric fundus and body and preservation of the antral pump provide a reasonable explanation for this finding. A secondary effect of earlier distal bowel stimulation with nutrients after meals due to increased gastric emptying time may be similar to the effects seen after gastric bypass.
Several mechanistic studies have demonstrated early and exaggerated postprandial peak levels of Peptide YY3–36 and GLP-1 after LSG. GLP-1 is an incretin that stimulates insulin production and releases from pancreatic islet cells, and the increased PYY3–36 results in satiety and reduced food intake. Karamanakos et al. have independently shown that the sleeve gastrectomy does have the effect of increasing the transit time of chyme despite an intact pylorus as measured by increased postprandial PYY levels.
Peterli et al. performed a randomized prospective trial with 13 LRYGB and 14 LSG patients to investigate the potential mechanism of LSG focusing on foregut and hindgut mechanisms. They found marked improvement in glucose homeostasis 1 week after surgery in both groups. This improvement was associated with early, exaggerated increases in GLP-1 secretion at 1 week, 3 months, and 1 year postoperatively in both groups. In addition to changes in GLP-1, PYY increased significantly and ghrelin was suppressed in both groups. It is unclear whether PYY has a direct effect on glucose homeostasis or if its effects are exhibited via appetite reduction and concomitant weight loss. Preoperatively, some patients had a blunted PYY and GLP-1 response suggesting some “resistance” to these gut hormones in obese patients. These findings suggest that the LSG should not be viewed merely as a restrictive procedure but also as a procedure that has neurohormonal and incretin effects.
Gastric Bypass versus Laparoscopic Sleeve Gastrectomy
Ramon et al. compared the effects of LRYGB and LSG on glucose metabolism and levels of gastrointestinal hormones such as ghrelin, leptin, GLP-1, peptide YY (PYY), and pancreatic polypeptide (PP) in morbid obese patients. This prospective, randomized study confirmed that the postprandial response of ghrelin, GLP-1, and PYY was maintained in patients undergoing LSG for 12 months after surgery and was similar to the LRYGB group results. A prospective, randomized study by Woelnerhanssen et al. compared the 1-year results of LRYGB and LSG for weight loss, metabolic control, and fasting adipokine levels. The authors confirmed a close association of specific adipokines with obesity and with the changes observed with weight loss after two different bariatric surgical procedures. The concentrations of circulating leptin levels decreased by almost 50 % as early as 1 week postoperatively and continued to decrease until 12 months postoperatively and adiponectin increased progressively. No differences were found between the LRYGB and LSG groups regarding adipokine changes.
How to choice a procedure?
The choice of procedure is an important determinant of outcome with a decreasing gradient of efficacy predicted from BPD, RYGB to SG and then LAGB. Other factors that have been positively correlated with diabetes remission are percentage of excess weight loss (% EWL), younger age, lower preop HbA1c, and shorter duration of diabetes (less than 5 years). Severity of diabetes, as judged by preop treatment modality, has also been noted to be a significant factor.
Schauer et al. have reported in their series of 191 obese diabetic patients (the majority of whom were on oral agents or insulin) a diabetes remission rate of 97 % in diet-controlled, 87 % in oral agent treated, and 62 % in insulin-treated subjects. This was also confirmed by a recent retrospective analysis of 505 morbidly obese diabetic patients who underwent RYGB. In this study, a more recent diagnosis of T2DM and the absence of preoperative insulin therapy were significant predictors of remission, independent of the percentage of EWL.
Dixon et al. have recently identified diabetes duration < 4 years, BMI > 35 kg/m2, and fasting c-peptide concentration > 2.9 ng/ mL as three clinically useful cutoffs and independent preoperative predictors of remission after analyzing the outcomes of 154 ethnic Chinese subjects after gastric bypass. C-peptide > 3 ng/mL has also previously been shown to be an important predictor of diabetes resolution after sleeve gastrectomy in non-morbidly obese diabetic subjects by Lee et al.
Pathophysiology of Sleeve Gastrectomy
Sleeve gastrectomy (SG), or longitudinal gastric resection, consists in a resection of the greater curvature of the stomach. In bariatric surgery, it was introduced by Hess in 1988 and by Marceau in 1990 as a component of the biliopancreatic diversion with duodenal switch (BPD/DS). Resecting the greater curvature of the stomach was aimed at reducing the risk of ulcer at the level of the duodeno-ileal anastomosis of the BPD/ DS. In fact, for those authors, the amount of stomach removed was estimated to be roughly 60% and the restriction was moderate. With a view to reducing the mortality associated with laparoscopic BPS/DS in super-super-obese patients, Regan et al. described a 60-French (F) bougiecalibrated isolated sleeve gastrectomy (ISG) as a first step in a two-stage program of laparoscopic BPD/DS in 2000. Since then, primary ISG has gained popularity in a staged surgery program for high-risk patients. Although medium- to long-term results are not known, and some technical details are still being discussed, the good short-term results obtained regarding weight loss, as well as co-morbidity and the acceptable rate of complications, have broadened the indications for primary ISG and assured its place in the armamentarium of bariatric surgical procedures. In June 2007, a position statement on SG as a bariatric procedure was endorsed by the ASMBS, and in October 2007 the First International Consensus Summit for Sleeve Gastrectomy was held in New York City.
As expected, the operation is restrictive (satiety occurs very quickly). Indeed, with the current calibration of the sleeve, its volume is less than 10% of the entire stomach and its distensibility is 10 times less than that of the resected stomach and fundus. Nevertheless, after 6 months, patients can cope with a mug-sized meal (200 ml) of solid food. Even if the size of the meal is small, the volume of the remaining stomach is larger by far than after purely restrictive procedures (gastric banding, vertical banded gastroplasty). Melissas et al. demonstrated an accelerated gastric emptying of solid food into the duodenum and the intestine at 6 and 24 months, and this could explain some enterohormonal changes . In addition to these mechanical effects, SG has hormonal effects. This operation is “anorexigenic”; the patients feel little hunger and have only a mild interest in eating. Most of them could skip a meal each day for at least 1 year after surgery. The fundus is known to be the major source of ghrelin, an orexigenic hormone. It has been proved that the level of ghrelin is dramatically reduced after the currently performed SG with the entire fundus resected, and to a higher degree than with gastric banding or gastric bypass. Other hormonal changes have been noted, such as a rise in the level of fasting PYY or GLP1, a hormone that induces also a feeling of satiety. This latter point has yet to be assessed in human beings. These incretin modifications could play a role in the remarkable short-term effects observed on diabetes. Thus it appears that LSG is a multifactorial procedure with a mild restrictive aspect and a complex neurohormonal aspect.