Newer Techniques in Bariatric Surgery for Morbid Obesity

Transcription

1 Technology Evaluation Center Newer Techniques in Bariatric Surgery for Morbid Obesity Assessment Program Volume 18, No. 10 September 2003 Executive Summary Morbid obesity, generally defined as a body-mass index (BMI) of 40 kg/m 2 or greater, is associated with excess mortality and a high burden of obesity-related morbidities. Nonsurgical treatments (i.e., lifestyle modifications, behavioral therapy, medications) have limited success in achieving substantial weight loss for morbidly obese patients. Surgical treatment has been employed for several decades, and a large number of clinical series have demonstrated success in achieving substantial weight loss (see the accompanying TEC Special Report The Relationship between Weight Loss and Changes in Morbidity Following Bariatric Surgery for Morbid Obesity ). Gastric bypass with Roux-en-Y anastomosis has been considered the bariatric surgery of choice in the U.S, and this is supported by a substantial body of literature. Comparative trials have shown gastric bypass with Roux-en-Y anastomosis to be superior to alternative procedures such as vertical banded gastroplasty (9 studies, n=3,780), horizontal gastroplasty (2 studies, n=261), and open gastric banding (2 studies, n=283). Roux-en-Y gastric bypass achieves greater weight loss and can be performed with low rates of morbidity and mortality. In recent years, less-invasive techniques have been applied to bariatric surgery, and offer potential benefits compared to open gastric bypass. Laparoscopic gastric bypass has the potential to reduce short-term morbidity while retaining the beneficial effects of gastric bypass. Laparoscopic gastric banding is less technically complex than other procedures, thus potentially lowering short-term complications even further. Laparoscopic banding has the additional advantage of reversibility, which is unique among bariatric surgery procedures. Another recent trend is the use of variations on gastric bypass (e.g., bilio-pancreatic diversion, longlimb gastric bypass) in attempts to maximize weight loss patients with super-obesity (BMI >50 kg/m 2 ). The purpose of this Assessment is to determine whether less-invasive procedures (laparoscopic gastric bypass, laparoscopic gastric banding) improve outcomes as compared to open gastric bypass, and whether variations on gastric bypass (e.g., bilio-pancreatic diversion, long-limb gastric bypass) improve outcomes for patients with super-obesity. BlueCross BlueShield Association An Association of Independent Blue Cross and Blue Shield Plans Based on the available evidence, the Blue Cross and Blue Shield Association Medical Advisory Panel made the following judgments about whether newer approaches to bariatric surgery for patients with morbid obesity meet the Blue Cross and Blue Shield Association Technology Evaluation Center (TEC) criteria. NOTICE OF PURPOSE: TEC Assessments are scientific opinions, provided solely for informational purposes. TEC Assessments should not be construed to suggest that the Blue Cross Blue Shield Association, Kaiser Permanente Medical Care Program or the TEC Program recommends, advocates, requires, encourages, or discourages any particular treatment, procedure, or service; any particular course of treatment, procedure, or service; or the payment or non-payment of the technology or technologies evaluated Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 1

2 Technology Evaluation Center 1. The technology must have final approval from the appropriate governmental regulatory bodies. The interventions under consideration are surgical procedures and are not subject to U.S. Food and Drug Administration (FDA) regulations. However, certain devices that may be used as part of the procedure may be subject to FDA approval. The Lap-Band system received Premarket Application (PMA) approval by the FDA in June 2001 for use in morbidly obese patients. No other devices are currently FDA-approved for use in bariatric surgery. 2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes. The evidence is not sufficient to form conclusions about the relative efficacy and morbidity of less-invasive approaches to bariatric surgery, specifically laparoscopic gastric bypass and laparoscopic gastric banding. There is a lack of high-quality clinical trials that directly compare these procedures with open gastric bypass; the available evidence consists largely of clinical series of individual procedures. This creates considerable difficulties in comparing outcomes of different procedures due to variability in patient populations, individual surgeons and hospitals, and secular trends in general surgery over time. Also, there is a lack of consistency in reporting outcomes, especially for adverse events, and only a relatively small number of patients included at longerterm follow-up times (e.g., 3 years or longer). The evidence allows crude comparisons of weight loss outcomes between procedures at 1 year, but is not sufficiently robust to make meaningful comparisons at longer time intervals. The evidence is also not adequate to determine comparative rates of adverse events. For laparoscopic gastric bypass, the available evidence suggests that weight loss outcomes are similar to open gastric bypass at 1 year. Because of the technical complexity of this operation, there is concern for short-term complications such as anastomotic leaks. Leakage of intestinal contents causes peritonitis, which can be life threatening and usually requires reoperation. The comparative rates of these serious adverse events cannot be determined from the data, leaving considerable uncertainty as to the relative safety of laparoscopic bypass. There are very little data on outcomes longer than 1 year for this procedure. For laparoscopic gastric banding, the available evidence suggests that weight loss at 1 year is less than that achieved with gastric bypass. More limited evidence on 3-year weight loss suggests that this difference in weight loss may lessen over time. Early adverse event rates are low following laparoscopic gastric banding, and are probably lower than gastric bypass. There is a higher rate of long-term adverse events, and there are a number of potentially serious long-term adverse events such as band slippage or erosion. The incidence of slippage of the device from its intended location or erosion through the gastric wall increases over time and can result in visceral organ damage, abdominal pain, and intestinal obstruction. The available data are not sufficient to determine the rates of these longer-term adverse events with confidence. There are limited data on outcomes of bilio-pancreatic diversion and/or long-limb gastric bypass for patients with super-obesity. There are no high-quality comparative trials and only limited clinical series data for these indications. These limited data do not establish that these or other variants (e.g., duodenal switch) have any additional benefit for patients with super-obesity, as compared to gastric bypass. 3. The technology must improve the net health outcome; and 4. The technology must be as beneficial as any established alternatives. There is insufficient evidence to conclude whether these procedures (i.e., laparoscopic gastric bypass, laparoscopic gastric banding, bilio-pancreatic diversion, long-limb gastric bypass) either improve the net health outcome or whether they are as beneficial as current established surgery, open gastric bypass with Roux-en-Y anastomosis Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited.

3 Newer Techniques in Bariatric Surgery for Morbid Obesity 5. The improvement must be attainable outside the investigational settings. Whether these procedures (i.e., laparoscopic gastric bypass, laparoscopic gastric banding, bilio-pancreatic diversion, long-limb gastric bypass) improve health outcomes has not been demonstrated in the investigational setting. Based on the above, laparoscopic gastric bypass, laparoscopic gastric banding, bilio-pancreatic diversion, or long-limb gastric bypass do not meet the TEC criteria. Contents Assessment Objective 4 Background 4 Methods 12 Formulation of the Assessment 14 Review of Evidence 15 Summary of Application of the 31 Technology Evaluation Criteria References 38 Appendix 41 Published in cooperation with Kaiser Foundation Health Plan and Southern California Permanente Medical Group. TEC Staff Contributors Lead Author Frank Lefevre, M.D.; Co-Author Naomi Aronson, Ph.D.; TEC Executive Director Naomi Aronson, Ph.D.; Managing Scientific Editor Kathleen M. Ziegler, Pharm.D.; Research/Editorial Staff Claudia J. Bonnell, B.S.N., M.L.S.; Maxine A. Gere, M.S. Acknowledgments Staff would like to thank James Flaherty, M.D., for his contributions to the research and development of this Assessment. Blue Cross and Blue Shield Association Medical Advisory Panel Allan M. Korn, M.D., F.A.C.P. Chairman, Senior Vice President, Clinical Affairs/Medical Director, Blue Cross and Blue Shield Association; David M. Eddy, M.D., Ph.D. Scientific Advisor, Senior Advisor for Health Policy and Management, Kaiser Permanente, Southern California. Panel Members Peter C. Albertsen, M.D., Professor, Chief of Urology, and Residency Program Director, University of Connecticut Health Center; Edgar Black, M.D., Vice President, Chief Medical Officer, BlueCross BlueShield of the Rochester Area; Helen Darling, M.A., President, Washington Business Group on Health; Josef E. Fischer, M.D., F.A.C.S., Mallinckrodt Professor of Surgery, Harvard Medical School and Chair, Department of Surgery, Beth Israel Deaconess Medical Center American College of Surgeons Appointee; Alan M. Garber, M.D., Ph.D., Professor of Medicine, Economics, and Health Research and Policy, Stanford University; Steven N. Goodman, M.D., M.H.S., Ph.D., Associate Professor, Johns Hopkins School of Medicine, Department of Oncology, Division of Biostatistics (joint appointments in Epidemiology, Biostatistics, and Pediatrics) American Academy of Pediatrics Appointee; Michael A.W. Hattwick, M.D., Woodburn Internal Medicine Associates, Ltd. American College of Physicians Appointee; I. Craig Henderson, M.D., Adjunct Professor of Medicine, University of California, San Francisco; Albert R. Jonsen, Ph.D., Professor Emeritus of Ethics in Medicine and former Chair, Department of Medical History and Ethics, University of Washington School of Medicine; Barbara J. McNeil, M.D., Ph.D., Ridley Watts Professor and Head of Health Care Policy, Harvard Medical School, Professor of Radiology, Brigham and Women s Hospital; Brent O Connell, M.D., M.H.S.A., Vice President and Medical Director, Pennsylvania Blue Shield/Highmark, Inc.; Stephen G. Pauker, M.D., M.A.C.P., F.A.C.C., Sara Murray Jordan Professor of Medicine, Tufts University School of Medicine; and Vice-Chairman for Clinical Affairs and Associate Physician-in-Chief, Department of Medicine, New England Medical Center; William R. Phillips, M.D., M.P.H., Clinical Professor of Family Medicine, University of Washington American Academy of Family Physicians Appointee; Thomas J. Ryan, M.D., M.A.C.P., M.A.C.C., Senior Consultant in Cardiology, the University Hospital, Boston University Medical Center; and Professor of Medicine, Boston University School of Medicine; Earl P. Steinberg, M.D., M.P.P., President, Resolution Health, Inc.; Paul J. Wallace, M.D., Executive Director, Care Management Institute, Kaiser Permanente; Jed Weissberg, M.D., Associate Executive Director for Quality and Performance Improvement, The Permanente Federation. CONFIDENTIAL: This document contains proprietary information that is intended solely for Blue Cross and Blue Shield Plans and other subscribers to the TEC Program. The contents of this document are not to be provided in any manner to any other parties without the express written consent of the Blue Cross and Blue Shield Association Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 3

4 Technology Evaluation Center Assessment Objective Morbid obesity, generally defined as a bodymass index (BMI) of 40 kg/m 2 or greater, is associated with excess mortality and a high burden of obesity-related morbidities. Nonsurgical treatments (i.e., lifestyle modifications, behavioral therapy, medications) have limited success in achieving substantial weight loss for morbidly obese patients. Surgical treatment has been employed for several decades, and a large number of clinical series have demonstrated success in achieving substantial weight loss (see the accompanying TEC Special Report The Relationship between Weight Loss and Changes in Morbidity Following Bariatric Surgery for Morbid Obesity ). Gastric bypass with Roux-en-Y anastomosis has been considered the bariatric surgery of choice in the U.S, and this is supported by a substantial body of literature. Comparative trials have shown gastric bypass with Roux-en-Y anastomosis to be superior to alternative procedures such as vertical banded gastroplasty (9 studies, n=3,780), horizontal gastroplasty (2 studies, n=261), and open gastric banding (2 studies, n=283). Roux-en-Y gastric bypass achieves greater weight loss and can be performed with low rates of morbidity and mortality. In recent years, less-invasive techniques have been applied to bariatric surgery, and offer potential benefits compared to open gastric bypass. Laparoscopic gastric bypass has the potential to reduce short-term morbidity while retaining the beneficial effects of gastric bypass. Laparoscopic gastric banding is less technically complex than other procedures, thus potentially lowering short-term complications even further. Laparoscopic banding has the additional advantage of reversibility, which is unique among bariatric surgery procedures. Another recent trend is the use of variations on gastric bypass (e.g., bilio-pancreatic diversion, long-limb gastric bypass) in attempts to maximize weight loss patients with super-obesity (BMI >50 kg/m 2 ). The purpose of this Assessment is to determine whether less-invasive procedures (laparoscopic gastric bypass, laparoscopic gastric banding) improve outcomes as compared to open gastric bypass, and whether variations on gastric bypass (e.g., bilio-pancreatic diversion, longlimb gastric bypass) improve outcomes for patients with super-obesity. Background Obesity Obesity is a growing problem worldwide; in the U.S., it is estimated that approximately 60 million individuals are obese (Balsiger et al. 2000). The current classification of obesity is based on the body mass index (BMI), defined as the weight in kilograms divided by the square of the height in meters (kg/m 2 ). BMI has achieved widespread acceptance for the classification of obesity because it correlates more closely with direct measurements of body fat in the laboratory than other measures using weight and height (Kral 2001). Table 1 shows the current guidelines for classifying patients by BMI. Table 1. Classification of Obesity * Obesity Class BMI (kg/m 2 ) Health Risk Underweight <18.5 Increased Normal Normal Overweight Increased Obese Mild I High Moderate II Very high Severe III 40.0 Extremely high (Super-Obese) ** IV 50.0 Extremely high *Adapted from Klein 2001 **Not included in original classification Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited.

5 Newer Techniques in Bariatric Surgery for Morbid Obesity Severe, or morbid obesity, is defined by a BMI of 40 kg/m 2 or greater and has a prevalence in the U.S. of 6% for women and 2% for men (Balsiger et al. 2000). Patients with morbid obesity are considered by most experts to represent a distinct class of obese patients, with special needs and challenges and who require different, more aggressive approaches to weight loss (Kral 2001). A morbidly obese white man at age 20 can expect to live 13 years less than his counterpart with a normal BMI, which equates to a 22% reduction in life expectancy (Fontaine et al. 2003). Medical conditions associated with obesity increase in frequency and severity with increasing weight, and are, therefore, found with the highest prevalence in morbidly obese patients (NIH/NHLBI 1998). Nonsurgical treatments for patients with morbid obesity, such as lifestyle modifications, behavioral therapy, and medications, are recommended prior to considering surgery. Unfortunately, nonsurgical approaches seldom succeed over the long term for the morbidly obese (NIH/NHLBI 1998), and it is, therefore, unlikely that these types of interventions will have a substantial impact on health outcomes. Therefore, surgery is considered by many experts to be the treatment of choice for this population. Bariatric Surgery for Morbid Obesity Bariatric surgery has been available as a treatment for obesity for several decades, and National Institutes of Health (NIH) guidelines for surgical treatment of obesity state that surgery should be considered for patients with a BMI greater than 40 kg/m 2 (or greater than 35 kg/m 2 with life-threatening co-morbidity) who have failed conservative treatment, are motivated, and well-informed (NIH guidelines 1991). These guidelines maintain that patients should undergo a thorough preoperative workup that includes psychological evaluation, and that follow-up after surgery should be life-long. Some of the different surgical techniques currently in use are shown in Figure 1. The different procedures are often classified into restrictive or malabsorptive procedures. Restrictive procedures reduce the size of the stomach reservoir, causing limitations in the amount of food ingested by mechanical means and early satiety. Malabsorptive techniques reduce the ability of the GI tract to absorb food, through bypassing specific portions of the GI tract. Some operations, such as gastric bypass with Roux-en-Y, combine elements of restrictive surgery with malabsorptive surgery. These are sometimes classified as complex operations in comparison with simple restrictive operations that only partition the stomach. A previous Technology Evaluation Center (TEC) evaluation completed in 1988 concluded that two open surgical procedures, gastric bypass and vertical banded gastroplasty, met the TEC criteria for improved net health outcome (Blue Cross and Blue Shield Association Technology Evaluation Center 1988). During the last several decades there has been a continued evolution in surgical techniques. Some of the original procedures, such as jejunal-ileal bypass, have been abandoned due to high rates of long-term adverse effects. For the purposes of this Assessment, surgical techniques will be divided into 3 categories. Established procedures, of which gastric bypass is considered the gold standard, will refer to open surgical procedures that have been in use for a considerable period of time. Minimally invasive procedures will refer to less-invasive modifications of established procedures. Alternative procedures will refer to variations of gastric bypass that are intended for specific subpopulations, such as patients with superobesity (i.e., BMI greater than 50 kg/m 2 ). This Assessment will attempt to determine the relative efficacy of minimally invasive and alternative procedures, in comparison to the gold standard, established procedure, gastric bypass. Established Procedures Surgical procedures in this class include gastric bypass with Roux-en-Y anastomosis, vertical banded gastroplasty, horizontal gastroplasty, and open gastric banding. Gastric Bypass with Roux-en-Y Anastomosis. Gastric bypass with Roux-en-Y anastomosis is considered by most experts to have the most favorable benefit/risk ratio and is currently the most common bariatric procedure performed in North America, accounting for 70% of bariatric surgery procedures in a 1999 survey (Schauer and Ikramuddin 2001). In this procedure, the majority of the stomach is resected (subtotal gastrectomy) and the gastric outlet is attached to the mid-portion of the jejunum. Alternatively, gastric partitioning by stapling may be used in place of gastric resection. The gastric partitioning reduces the amount of food that can be ingested, and the Roux-en-Y anastomosis 2003 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 5

6 Technology Evaluation Center Figure 1. Bariatric Surgery Procedures (Adapted from Esophagus Staples Esophagus Band Small Pouch Stomach Small Stomach Pouch Duodenum Duodenum Stomach A. Roux-en-Y Gastric Bypass. A Roux limb is anastomosed end-to-side to a gastric pouch. The proximal jejunal (biliopancreatic) limb is anastomosed end-to-end to the Roux limb. B. Gastric Banding. A gastric band placed around the proximal stomach to create the partitioning. Esophagus Small Stomach Pouch Staples Remainder of Partially Removed Pouch Duodenum Jejunum Band Leum Stomach Duodenum Colon C. Vertical Banded Gastroplasty. A vertical gastric pouch is constructed by a stapler. The pouch outlet (stoma) is reinforced with a mesh collar. D. Biliopancreatic Bypass. After a subtotal gastrectomy, the distal alimentary (Roux) limb is anastomosed to the proximal gastric remnant. The biliopancreatic (jejunum to proximal ileum) limb is anastomosed end-to-side to the distal ileum Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited.

7 Newer Techniques in Bariatric Surgery for Morbid Obesity allows food to bypass the duodenum and proximal jejunum (Balsiger et al. 2000) resulting in global malabsorption over the bypassed portion of the intestine. Open gastric bypass is a major surgical procedure, with the attendant risks and recovery period expected with intraperitoneal surgery. Adverse effects of gastric bypass also include complications specific to the procedure, such as leaks or obstruction at the anastomotic sites. In addition, dietary modifications are necessary to achieve a successful outcome. For example, the dumping syndrome, defined as abdominal symptoms and diarrhea shortly after eating, is due to reduced transit time in the intestine, and patients must eat small meals to ameliorate these symptoms. Due to the altered passage of food, patients are also at risk for a number of metabolic complications, including iron deficiency anemia, vitamin B 12 deficiency, and hypocalcemia. These potential adverse effects are summarized in Table 2. A substantial body of literature supports the superiority of open gastric bypass with Rouxen-Y anastomosis over other established procedures (Schauer and Ikramuddin 2001). The available comparative studies that compare gastric bypass with other established procedures are summarized in Table 3 (see also Appendix Table I). The majority of comparative studies compare gastric bypass with vertical banded gastroplasty, with a few studies comparing other types of gastroplasty and/or gastric banding. In these studies, gastric bypass consistently achieves greater amounts of weight loss compared to alternative procedures, without any demonstrable increases in morbidity or mortality. The most rigorous of these comparative trials, the Adelaide Study (Hall et al. 1990), randomized 310 morbidly obese patients to gastric bypass, vertical banded gastroplasty, or horizontal gastroplasty. The percent of patients with greater than 50% excess weight loss (EWL) at 3 years follow-up was 67% for gastric bypass, 48% for vertical banded gastroplasty, and 17% for horizontal gastroplasty (p<0.001). There were no demonstrable differences in adverse events between groups. A large number of clinical series of patients undergoing gastric bypass have been published in the literature, and this body of literature affords the best estimates of the amount of weight loss following gastric bypass. Tables 4 6 summarize the weight loss and adverse events outcomes found in two systematic reviews of these single-arm studies of gastric bypass (Chapman et al. 2002; ProMed 2001), together with the weight loss outcomes for the comparative trials reviewed for this TEC Assessment (Table 3). These analyses report relatively consistent ranges of the percent EWL at year, with an overall range of 62 78%. Adverse effects of gastric bypass are not as consistently reported as weight loss outcomes, and it is more difficult to obtain precise estimates of adverse event rates. The rates of potential adverse events from this evidence are summarized in Tables 5 and 6, divided into short-term adverse effects and long-term adverse effects. Vertical Band Gastroplasty. Vertical band gastroplasty (VBGP) is a restrictive procedure, in which a small pouch is created in the upper stomach by stapling. The pouch communicates with the remainder of the stomach via a narrow channel called a stoma (Figure 1C). The stoma is reinforced by an external wrap made of prosthetic mesh. VBGP achieved popularity because of its technical ease and low morbidity. Mortality following VBGP is less than 1%. Short-term complications of these procedures include those associated with upper abdominal surgery, such as injuries to internal organs, injuries to the gastrointestinal tract, bleeding, cardiopulmonary complications, intra-abdominal and/or wound infections, and thromboembolic events. Complications can include gastric obstruction, leaks or failure at the staple line, and nausea/vomiting caused by the altered stomach physiology. Long-term complications can include persistent nausea/vomiting, gastroesophageal reflux disease (GERD), failure of the staple line, wound dehiscence, stenosis at the gastric outlet site, band slippage, band erosion, and dilation of the stomach pouch. Malnutrition and vitamin deficiencies are also a long-term concern. Horizontal Gastroplasty. Horizontal gastroplasty (HGP) is a restrictive procedure that involves partitioning the stomach into two parts by creating a small upper pouch connected to the remainder of the stomach via a narrow stoma. In horizontal gastroplasty, staples are placed transversely across the entire stomach, creating a gastrogastrostomy (channel between upper and lower portions of stomach). Mortality following HGP is less than 1%. Shortterm complications of these procedures include 2003 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 7

8 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. Table 2. Potential Adverse Effects Following Gastric Bypass Short-term Adverse Events Long-term Adverse Events Dietary Modifications Intraoperative: Bowel perforation Bleeding Splenic injury Anastigmatic leaks Early postoperative: Death Cardiopulmonary complications Thromboembolic complications Bowel obstruction Wound infection Reoperations Readmission to hospital Incisional hernia Staple line failure Anastomotic problems Dilated pouch Marginal ulcer Gastritis Cholecystitis Dehydration/malnutrition Depression Vitamin/mineral deficiencies Iron Folate B 12 Small meals Early satiety Dumping syndrome Avoid high-calorie liquids or snacks Daily vitamin supplementation Technology Evaluation Center

9 2003 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 9 Table 3. Summary Table of Comparative Trials of Gastric Bypass vs. Other Established Surgical Procedures (condensed from Appendix Table I) # of Studies/ Gastric Bypass vs.: # of Patients Effect on Weight Loss Short-term Adverse Effects Long-term Adverse Effects Vertical-banded gastroplasty (VBGP) 9 studies 3,780 pts 9/9 trials show larger weight loss with gastric bypass: 44 70% improvement in total kg loss 28 43% improvement in EWL 19 36% more pts with >50% EWL Horizontal 2 studies 2/2 trials show larger weight loss with gastroplasty 261 patients gastric bypass: % greater total kg loss 49% more pts with >50% EWL Gastric banding 2 studies 2/2 trials show larger wt loss with gastric 283 patients bypass: 13.3 kg greater total wt loss 39% more pts with >50% EWL Silastic ring 1 study 1/1 study shows larger weight loss with gastroplasty (SRGP) 817 patients gastric bypass but data limited (registry data only): 34% improvement in EWL Abbreviations Key in Appendix Limited data: Limited data: low overall mortality and inconsistent reporting, serious complications high rates of symptoms, e.g., vomiting more complications in gastric when reported (18 57%) in both groups bypass group higher rates of revision in VBGP group data insufficient for rigorous comparative analysis Limited data: Limited data: low overall mortality and no clear trends on serious complications comparative frequency data insufficient for rigorous data insufficient for rigorous comparative analysis comparative analysis No data on adverse effects reported No data on adverse effects reported in either trial in either trial Limited data on postoperative No data reported on long-term complications: complications gastric bypass 2.6% SRGP 1.2% Newer Techniques in Bariatric Surgery for Morbid Obesity

10 Technology Evaluation Center Table 4. Weight Loss Outcomes Following Open Gastric Bypass % EWL 1 yr. 3 yrs. 5 yrs. Comparative studies (n=9) Range Median NR Systematic review #1 (Chapman) (n=7 * ) Range Median NR Systematic review #2 (ProMed) (n=6 * ) Range Median NR NR NR Overall Range * Excluding studies with <100 patients enrolled Abbreviations Key in Appendix Table 5. Gastric bypass with Roux-en-Y: Short-term Adverse Outcomes Perioperative Complications Study/Yr Death Perf Leak Bleed Obstr Throm Card Wound Comparative studies (n=9) Range 0 5% 0 3% 0 3% 0 3% 0 10% Systematic review #1 (Chapman) (n=7) 0.5% 1.0% 0.4% 0.4% 1.1% 0.2% 0.4% 4.5% Systematic review #2 (ProMed) (n=6) Range 0 0.6% NR NR NR NR NR NR NR Abbreviations Key in Appendix Table 6. Gastric Bypass with Roux-en-Y: Long-term Adverse Outcomes Long-term Complications Study/Yr Reop Sten Obstr Ulcer Nutr N/V Hern Chol Comparative studies (n=9) Range 0 35% 0 0% 3 9.5% 2 9% Systematic review #1 (Chapman) (n=7) Range % 4.8% 1.0% 4.1% 6.0% NR 0.3% 1.7% Systematic review #2 (ProMed) (n=6) Range % NR NR NR NR NR NR NR Abbreviations Key in Appendix Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited.

11 Newer Techniques in Bariatric Surgery for Morbid Obesity those associated with upper abdominal surgery, such as injuries to internal organs, injuries to the gastrointestinal tract, bleeding, cardiopulmonary complications, intra-abdominal and/or wound infections, and thromboembolic events. Complications can include gastric obstruction, leaks or failure at the staple line, and nausea/ vomiting caused by the altered stomach physiology. Long-term complications can include persistent nausea/vomiting, gastroesophageal reflux disease (GERD), failure of the staple line, wound dehiscence, stenosis at the gastric outlet site, band slippage, band erosion, and dilation of the stomach pouch. Malnutrition and vitamin deficiencies are also a long-term concern. Gastric Banding. Gastric banding is a restrictive procedure that works via a prosthetic device that is wrapped around a portion of the stomach. Adjustable gastric banding refers to bands in which the pressure can be varied without an invasive procedure. Gastric banding is less technically complex compared to other bariatric surgery procedures, since the band is entirely external to the stomach and can be adjusted without entering the gastric cavity. This procedure is entirely reversible by removal of the prosthetic band. Placement of the gastric band by open surgical techniques is seldom performed in current practice, as laparoscopic techniques have supplanted open surgery for band placement. Short-term complications of gastric banding are expected to be low, but can occur. There is a risk of organ injury, bowel perforation and/or bleeding, pulmonary complications and intra-abdominal infections. Similar to other restrictive procedures, longer-term complications can occur. Nausea and vomiting can result, especially if the band pressure is too high. Dilation of the pouch may occur, usually resulting in weight gain. GERD may occur due to the increased pressure gradient introduced in the stomach. These complications may respond to adjustment of the band pressure. Other long-term complications can as a result of the prosthetic device. There may be slippage of the device, and over time, the device may erode through the gastric wall. Malnutrition and vitamin deficiencies may also occur as long-term complications. Minimally Invasive Procedures Minimally invasive procedures have been developed for gastric bypass and for adjustable gastric banding. These less-invasive procedures are intended to reduce short-term morbidity and to lessen recovery time. Potential adverse events of the procedure are the same as with the open technique. However, the incidence and sequelae of these adverse events may differ between open and laparoscopic approaches, due to variations in the technical aspects of the procedures. Laparoscopic Gastric Bypass. Laparoscopic gastric bypass intends to reproduce the open procedure via minimally invasive techniques. This is a technically complex operation that requires a dedicated team and a relatively high degree of skill and experience in laparoscopic surgery. Five or 6 port access sites in the upper abdomen are used. Gastric partitioning and anastomoses of the proximal and roux limb are performed with laparoscopic instruments, and with limited direct visualization of the surgical field. In addition to the usual patient selection criteria, some surgeons will require additional criteria to be met in order to qualify for laparoscopic surgery. These may include: an absolute weight limit (e.g., BMI <50 kg/m 2 ), no previous abdominal surgery, no evidence of hypoventilation syndrome, and no evidence of liver enlargement. Laparoscopic Adjustable Gastric Banding. Laparoscopic adjustable gastric banding is a popular technique that has largely replaced open gastric banding. The literature includes reports of two types of adjustable gastric banding, the Lap-Band adjustable gastric band, and the Swedish adjustable gastric band. Both of these gastric bands are saline-filled devices that can be inflated or deflated via a reservoir attached to the band and are accessed through a port without an additional invasive procedure. The band is placed after dissection of the proximal stomach from adjacent structures and sutured in place to the stomach. Alternative Procedures These alternatives to gastric bypass, long-limb gastric bypass and bilio-pancreatic diversion, are generally targeted to specific subpopulations. Most notable are super-obese patients in whom greater amounts of weight loss may be needed to achieve similar outcomes. The intent for these procedures is to maximize the malabsorption component of the operation in order to achieve the greatest amount of weight loss possible Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 11

12 Technology Evaluation Center Long-limb Gastric Bypass. Long-limb gastric bypass (LLGBY) or distal gastric bypass, is identical to standard gastric bypass except for the length of the Roux-limb. Creation of a longer Roux-limb results in a greater portion of the small intestine being bypassed, thus increasing the degree of malabsorption. Perioperative mortality and short-term complications are therefore thought to be similar to standard gastric bypass. Long-term complications may differ, however, especially regarding nutritional and vitamin deficiencies caused by malabsorption. Bilio-pancreatic Diversion. Bilio-pancreatic diversion (BPD) is a combination restrictive/ malabsorption procedure that is intended to preferentially inhibit the absorption of fat. Bile acids and pancreatic enzymes, which are required for digesting fat, normally drain through the common bile duct into the duodenum. In BPD, the common bile duct drainage is diverted to a more distal location in the small intestine, thereby decreasing the time and distance that ingested food is exposed to these agents and limiting absorption. The procedure is usually combined with gastric bypass, since loss of the buffering action of bile salts on gastric acid causes an increased tendency for acid-related disorders, such as acid reflux or peptic ulcer disease. Mortality following BPD is probably in the 1 2% range. Short-term complications of BPD include those associated with upper abdominal surgery, such as injuries to internal organs, injuries to the gastrointestinal tract, bleeding, cardiopulmonary complications, intra-abdominal and/or wound infections, and thromboembolic events. Complications specific to the procedure can include gastric obstruction, leaks at the anastomotic sites, and nausea/vomiting caused by the altered stomach physiology. Anastomotic leaks are a serious complication that usually results in peritonitis and the need for an additional surgical procedure. Long-term complications can include persistent nausea/vomiting, GERD, leaks or stenoses at the anastomotic sites, wound dehiscence, dilation of the stomach pouch. Because this surgery is intended to cause a greater degree of malabsorption compared to gastric bypass, the possibility of malnutrition and/or vitamin deficiencies are a greater concern for patients undergoing this procedure. FDA Status. The interventions under consideration are surgical procedures and are not subject to U.S. Food and Drug Administration (FDA) regulations. However, certain devices that may be used as part of the procedure may be subject to FDA approval. The Lap-Band system received Premarket Application (PMA) approval by the FDA in June 2001 for use in morbidly obese patients. No other devices are currently FDA-approved for use in bariatric surgery. Health Outcomes in Obesity Research Weight loss is the most common outcome measure used in trials of obesity research, and can be expressed in a variety of ways (Table 7). Standardized measures of weight loss, such as the percent of excess weight loss, are more clinically meaningful than are absolute amounts of weight loss. For the purposes of this Assessment, all weight loss outcomes will be considered, but standardized measures that are commonly in use, particularly the percent excess weight loss and the decrease in BMI, will have the greatest utility in comparing results across studies. In determining the comparative benefit of different surgical procedures, weight loss outcomes will be considered together with adverse effects for each procedure. These outcomes are sufficient for making judgments, since virtually all of the improvements in health outcomes following surgery are mediated through weight loss. As a result, the magnitude of benefit following surgery is directly proportional to the amount of weight loss for any given procedure. The benefits of surgery in terms of weight loss will be balanced against the adverse effects of each procedure, both short term (perioperative) and long term (>30 days following surgery). Methods Search Methods The MEDLINE database was searched using the terms (all fields): obesity or obese or morbid obesity. These terms were cross-referenced with the terms (all fields): surgery or gastric band or roux-en-y or gastric resection or gastric bypass or bilio-pancreatic bypass, gastric band or adjustable gastric band or laparoscopic gastric band or gastric resection or bilio-pancreatic bypass or long-limb gastric bypass. Searches Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited.

13 Newer Techniques in Bariatric Surgery for Morbid Obesity Table 7. Variations in Reporting Weight Loss Outcomes Outcome Measure Definition Clinical Significance Decrease in weight Decrease in BMI % excess weight lost (%EWL) % patients losing >50% of excess body weight (EBW) % ideal body weight (%IBL) Abbreviations Key in Appendix Absolute difference in weight pre- and post-treatment Absolute difference in BMI pre- and post-treatment Amount of weight lost Excess body weight Number of pts losing >50% BW Total patients Final weight Ideal body weight Unclear relationship to outcomes, especially in morbidly obese May be clinically significant if change in BMI clearly leads to change in risk category Has anchor to help frame clinical significance; unclear threshold for clinical significance Additional advantage of framing on per patient basis. Threshold for significance (>50%) arbitrary Has anchor to help frame clinical significance; unclear threshold for clinical significance were performed on PubMed for the period of January 1985 through August 2003 and were limited to English language articles reporting on human subjects. Initial search was supplemented with the related articles function for several key trials. Computerized searches were supplemented by manual reviews of bibliographies of selected references, pertinent Cochrane reviews, and review of Current Contents. Citation abstracts were reviewed for relevance and all potentially relevant articles were reviewed in full. Study Selection Studies were selected for inclusion in this Assessment if they met the following criteria: 1. Full-length articles published in peerreviewed journals in the English language between 1985 and Patient population of adults with morbid obesity, as defined by: a. BMI >40 kg/m 2 b. BMI >35 kg/m 2 and at least one serious medical comorbidity, OR c. Similar measure of defining morbid obesity (e.g., >100% above ideal body weight) 3. Patients treated with one of the bariatric surgical procedures of interest (i.e., open gastric bypass, laparoscopic gastric bypass, laparoscopic gastric banding, bilio-pancreatic diversion, long-limb gastric bypass). 4. At least 1-year follow-up (except for short-term adverse events, for which this criterion did not apply) 5. Reports on at least one relevant outcome: a. Weight loss b. Adverse effects of surgery (early morbidity/mortality of procedure, long-term adverse effects due to altered GI anatomy and physiology). 6. Study design is: a. Comparative study with one or more comparisons of interest: i. open gastric bypass vs. laparoscopic gastric bypass, or ii. open gastric bypass vs. laparoscopic gastric banding, or iii. open gastric bypass vs. bilio-pancreatic diversion/long-limb gastric bypass for patients with super-obesity, and b. Includes at least 25 evaluable patients per treatment arm, OR: c. Single-arm study that reports on outcomes of i. laparoscopic gastric bypass, or ii. laparoscopic gastric banding, or iii. bilio-pancreatic diversion/long-limb gastric bypass for patients with super-obesity, AND: iv. includes at least 100 evaluable patients that were treated with particular procedure. For procedures intended for super-obese patients (bilio-pancreatic diversion, long-limb gastric bypass), studies were sought for this specific population. However, due to the lack of studies that focused exclusively on this population, inclusion criteria were not limited to 2003 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 13

14 Technology Evaluation Center super-obese populations for these procedures. In cases of multiple publications from a single study, the most recent or complete reporting of the results was used. Where different outcomes were reported in multiple publications, or when a subset of an overall population was reported in a separate publication, these outcomes were reported as part of the larger, overall study. Study Quality Assessment Study quality was formally assessed for comparative studies based on the quality assessment approach outlined by the United States Preventive Services Task Force (USPSTF; Harris et al. 2001). In this approach, 5 quality indicators are assessed as met or not met. These are: Initial assembly of comparable groups (adequacy of randomization, allocation concealment, and equal distribution of confounders among groups); Maintenance of comparable groups (attrition, crossovers, contamination, non-adherence); Comparable performance of and clear definition of interventions with equivalent attention and quality of care; Comparable measurements: unbiased, reliable, and valid (includes masking of outcome assessment); Appropriate analysis of outcomes. Intentto-treat analysis for randomized, controlled trials, consideration of confounding variables in nonrandomized studies. All important outcomes considered. An overall level of quality of good (meets all criteria), fair (does not meet all criteria but no fatal flaws ), or poor (has fatal flaws ) is assigned based on these 5 parameters. Medical Advisory Panel Review This Assessment was reviewed by the Blue Cross and Blue Shield Association Medical Advisory Panel (MAP) on June 3, In order to maintain the timeliness of the scientific information in this Assessment, literature search updates were performed subsequent to the Panel s review (see Search Methods ). These updated searches were confined to comparative studies, since the volume of single-arm studies published precludes performing rapid updates. If the search updates identified any additional studies that met the criteria for detailed review, and did not change the results of the Assessment, the results of these studies were included in the tables and text where appropriate. Formulation of the Assessment Patient Indications Patients are those with a BMI of >40 kg/m 2, or with a BMI of >35 kg/m 2 and serious weightrelated comorbidities, are candidates for bariatric surgery. In general, these patients will have failed conservative treatment, including lifestyle modifications and medications. However, because the expected success rate for these treatments in morbidly obese patients is low, most researchers do not consider this a necessary condition prior to attempting surgery. Super-obese patients are defined as patients with a BMI >50 kg/m 2. Some surgeons consider this to be a special subgroup of morbidly obese patients that warrant different approaches to bariatric surgery. For the purposes of this Assessment, super-obesity will be considered to be a potential indication for alternative bariatric surgery procedures, i.e., long-limb gastric bypass and/or bilio-pancreatic diversion. Technologies to Be Compared In evaluating the relative efficacy of surgical procedures, open gastric bypass with Roux-en-Y anastomosis will be considered the reference operation for comparison with other procedures. This Assessment will focus on particular comparisons with gastric bypass that are of current high interest. These are: 1. gastric bypass vs. laparoscopic gastric bypass 2. gastric bypass vs. laparoscopic gastric banding (Lap-Band or Swedish Adjustable Gastric Band) 3. gastric bypass vs. bilio-pancreatic diversion or variants (distal gastric bypass or long-limb gastric bypass) for patients with super-obesity Health Outcomes Weight loss is the most commonly reported outcome measure reported in trials of surgery for obesity, and is sufficient for comparing the relative efficacy of different procedures when combined with the adverse effects of surgery. For the purposes of this Assessment, all weight loss outcomes will be considered, but standardized measures that are commonly in use, particularly percent EWL and the decrease in BMI, will have the greatest utility in comparing results across studies. Adverse effects of surgery include the shortterm morbidity and mortality from the operation itself. Long-term adverse effects are related to symptoms caused by the altered Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited.

15 Newer Techniques in Bariatric Surgery for Morbid Obesity passage of food through the GI tract following surgery, and often persist indefinitely. Specific Assessment Questions What is the evidence for the relative benefit of other surgical procedures compared to gastric bypass? Question 1. Are outcomes of laparoscopic gastric bypass as good as outcomes of open gastric bypass for patients with morbid obesity, as judged by: Amount of weight loss Adverse events Question 2. Are outcomes of laparoscopic gastric banding (Lap-Band and/or Swedish Adjustable Gastric Band) as good as outcomes of open gastric bypass for patients with morbid obesity, as judged by: Amount of weight loss Adverse events Question 3: Are outcomes of bilio-pancreatic diversion and/or long-limb gastric bypass as good as outcomes of open gastric bypass for patients with super-obesity, as judged by: Amount of weight loss Adverse events Review of Evidence Following application of the selection criteria, 51 studies were included in the Review of Evidence. There were 6 comparative studies of gastric bypass to 1 or more of the procedures of interest: 3 compared open gastric bypass with laparoscopic gastric bypass, 1 compared open gastric bypass with laparoscopic gastric banding, and 2 compared open gastric bypass with bilio-pancreatic diversion or long-limb gastric bypass. A total of 45 single-arm studies met the inclusion criteria: 8 reporting on outcomes of laparoscopic gastric bypass, 32 reporting on outcomes of laparoscopic gastric banding, and 5 reporting on outcomes of biliopancreatic diversion/long-limb gastric bypass. Methodologic Considerations Conclusions regarding the comparative efficacy of different bariatric surgery techniques are best made from comparative trials, particularly trials with concurrent control groups and randomized treatment assignment. Despite the large quantity of literature published on outcomes of various bariatric surgical procedures, this body of literature lacks high-quality clinical trials that directly compare outcomes among different procedures. Although a few comparative studies exist, these are not high quality, and the literature is therefore dominated by single-arm studies that report outcomes of one procedure. As a result, there are a number of difficulties that arise in attempting to determine the comparative efficacy using data from single-arm series. Surgical procedures are inherently prone to variability between individual surgeons, especially for procedures that are technically complex. Variability in skill, expertise and training of individual surgeons for a particular procedure may affect both the beneficial and harmful outcomes of surgery. In addition, outcomes of a surgical procedure may vary between hospitals independent of the individual surgeon(s), due to the quality of the nursing and ancillary staff, the resources available, and the volume of procedures performed. The degree of impact that these factors have for bariatric surgery cannot be empirically demonstrated, but they have been shown to have a substantial impact on outcomes from other well-established surgical procedures such as coronary artery bypass grafting (CABG) (Choban et al. 1999). Lack of standardization in reporting outcomes also hinders the ability to compare outcomes between single-arm series. While reporting of weight-loss outcomes following bariatric surgery is fairly well standardized, the reporting of adverse events shows wide variability among the studies included in this Assessment. Systematic reporting of adverse events is unusual in this literature. Authors tend to classify adverse events in different ways, thus reporting different sets of adverse events at different points in time. The intensity of surveillance for adverse events may differ considerably, and systematic surveillance at regularly planned intervals is generally not done. For this Assessment, a set of the most important complications was defined for each procedure, divided into short-term (perioperative) and long-term adverse events. Data from each study on adverse events were then fit into these categories to the greatest extent possible. Numerous other sources of variability also have the potential to impact outcomes. Patient clinical characteristics may vary (demographics, average BMI, comorbidities), especially in 2003 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 15

16 Technology Evaluation Center situations where patient selection criteria differ, for example between open and laparoscopic gastric bypass. Psychological factors such as expectations from treatment may also differ between patient populations, and these factors may play a large role in outcomes of bariatric surgery. Secular trends in the field of surgery are also a consideration when studies are compared from different time periods and may further bias comparisons among single-arm studies. Improvements in technology, and/or systems of care over time cannot easily be accounted for in these comparisons. Question 1. Are outcomes of laparoscopic gastric bypass as good as outcomes of open gastric bypass for patients with morbid obesity, as judged by: Amount of weight loss Adverse events A total of 11 studies met the inclusion criteria for this question. There were 3 comparative studies of laparoscopic versus open gastric bypass enrolling 278 patients (129 patients receiving laparoscopic surgery, 149 patients receiving open surgery). Eight single-arm studies of laparoscopic bypass enrolling a total of 3,539 patients were also included. The 3 comparative studies (Table 8) were all rated of poor quality (see Appendix Table II). Westling and Gustavsson (2001) randomized patients to laparoscopic or open bypass, but the groups were imbalanced in number (30 vs. 21) and on baseline clinical characteristics (e.g., BMI 44.0 kg/m 2 vs. 41.0, p<0.05). This study represented the initial experience of the authors with the laparoscopic technique, and, thus, did not account for any effect of the learning curve. Nguyen et al. (2001) was also a randomized trial, but had a short follow-up, reporting their main outcomes at 6 months. One-year weight loss outcomes were reported for approximately one-third of the patients who had reached that time point. The third trial, See et al. (2002), was a nonrandomized comparison of patients at one institution who had received either laparoscopic or open bypass during two different time periods. Data from this trial were confined to comparisons of short-term adverse events for each procedure. Weight loss outcomes at 1 year were reported by Westling and Gustavsson (2001) and Nguyen et al. (2001), and were similar in both groups (Table 9). Adverse events were reported by all three studies, but these rates are limited by the small numbers of patients. Westling and Gustavsson (2001) reported higher rates of adverse events, both early and late, in the laparoscopic group (Table 10). Nguyen et al. (2001) and See et al. (2002) reported similar overall rates of adverse events, with some differences in the distribution (Table 10). However, due to the methodologic limitations of these studies, no conclusions can be drawn for either the weight loss or the adverse events outcomes. The single-arm studies (Table 11), ranging from 100 to 1,500 enrolled patients, included patients with a similar age (range 39 45), similar BMI (range kg/m 2 ) and a similar gender mix (range 10 19% male), but a length of follow-up that varied considerably (4 60 months). Most of the studies enrolled consecutive patients (7/8) and collected data prospectively (6/8). Only 2 of the studies were from the U.S. and only 3 reported a comprehensive preoperative workup. Six studies reported the %EWL at 1 year, with a range of 56 77% EWL (Table 12). This is similar to the range of 62 78% obtained for open gastric bypass. Although most studies reported %EWL at 1 year, there were large numbers of patients not included in the analysis. Five of the 8 studies (n=2476) reported the number of patients at follow-up, and only one-third (808/2476) of the total number of patients were included in the 1 year weight loss outcomes. For longer time periods, even fewer patients were available for analysis. For example, only one study reported weight loss outcomes at 3 years (Higa et al. 2001), and in this study only 1.3% of the enrolled patients were included (19/1,500). Adverse events were reported by all the studies, and overall rates of complications were estimated by summing the rates for all studies that reported that complication (Table 13). Death was infrequent, occurring with a range of 0 1%. Other early complications occurred with rates generally less than 10%, for example, a range of 1 6% for anastomotic problems, 0 4% for perforation of bowel or viscus, and 0 10% for gastric or intestinal obstruction. The rates for leaks and obstruction, which represent two of the most serious early complications, may be higher than for gastric bypass. The range of leaks reported in comparative studies of Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited.

17 2003 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 17 Table 8. Open Gastric Bypass vs. Laparoscopic Gastric Bypass Study Characteristics Study/Yr Patients Study Groups n Mean Age Mean BMI Westling and Gustavsson 2001 Randomized, controlled trial BMI >40, or BMI >35 with comorbidities Failed medical therapy Open gastric bypass Lap gastric bypass Nguyen et al Open gastric bypass 76 Randomized, controlled trial Lap gastric bypass 79 BMI Failed previous nonsurgical attempts at weight loss See et al Open gastric bypass 52 Retrospective, comparative Lap gastric bypass 20 clinical series All patients undergoing either open GB or lap GB in 1 year period * Significantly different from open group, p<0.05 Abbreviations Key in Appendix * F/U Mos. WTL MOR Outcomes OOL PSY ADV Comments > BMI 2. Postoperative complications (mean) Mean follow-up <1 yr, but 1. % EWL reported wt loss outcomes for pts 2. BAROS system with follow-up 1 yr (54/155) 3. Postoperative complications Reported only short-term outcomes (complications), no 1. Early complications weight loss outcomes. Newer Techniques in Bariatric Surgery for Morbid Obesity

18 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. Table 9. Open Gastric Bypass vs. Laparoscopic Gastric Bypass: Weight Loss Outcomes n Weight Loss Outcomes Study/Yr Treatment Groups (enr/eval) 1 year p value 3 year p value 5 year p value >5 year p value Westling and Gustavsson 2001 GBY 21 BMI: -13 ± 3 NS Lap GBY ± 3 Nguyen et al GBY 76/25 % EWL: 62 ± 14 NS Lap GBY 79/29 68 ± 15 Abbreviations Key in Appendix Table 10. Open Gastric Bypass vs. Laparoscopic Gastric Bypass Adverse Outcomes Perioperative Complications Long-term Complications n Study/Yr Group (enr/eval) Death Conv Perf Anas Bleed Obstr Thromb Card Wound Reop Anas Infect Ulcer Nutr N/V Hern Westling and Gustavsson 2001 GBY Lap GBY Nguyen et al. GBY Lap GBY 79 0 See et al GBY Lap GBY Technology Evaluation Center Abbreviations Key in Appendix

19 2003 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. 19 Table 11. Single-arm Studies: Laparoscopic Gastric Bypass with Roux-en-Y: Study Characteristics n at f/u (yrs) Mean Mean % F/U Study/Yr Age BMI Male (Mos.) n enrolled Preop (% available) Pro Con U.S. W/U WTL MOR QOL PHY PSY ADV Blachar 45.0 NR NR X et al (130 kg) Gould X X X X X et al (223) Papasavas X X X X et al (80) Dresel X X X et al DeMaria X X X X X et al (72) Higa et al X X X X Schauer X X X X X X et al Wittgrove and Clark 2000 NR NR NR NR X X X X X X Abbrevations Key in Appendix Outcomes Reported Newer Techniques in Bariatric Surgery for Morbid Obesity

20 Blue Cross and Blue Shield Association. Reproduction without prior authorization is prohibited. Table 12. Single-arm Studies: Laparoscopic Gastric Bypass with Roux-en-Y: Weight Loss Outcomes % EWL (yrs) Reduction in BMI (yrs) Study/Yr n enrolled (% available) Preop BMI Blachar et al Gould et al % (15) Frezza et al % (NR) Papasavas et al % (51) (51) Dresel 100 et al DeMaria et al % (69) (69) Higa et al % (572) 69% (51) 62% (19) Schauer et al % (101) 83% (19) (101) 20.8 (19) Wittgrove and Clark % (NR) 80% (NR) 75% (NR) 75% (NR) 80% (NR) Overall Range 56 77% 62 77% Technology Evaluation Center Abbreviations Key in Appendix