Traditionally, surgery focuses on an organ gone bad, afflicted with infection, cancer, trauma, or malfunction. In contrast, metabolic surgery is the operative manipulation of normal organs with the intent of effecting change in the body’s internal milieu to achieve a potential health gain. Originated in 1953, bariatric surgery is metabolic surgery. More than 50 bariatric procedures have been proposed and implemented, a sign of vigor and imagination in the field. As a result of time and trial, several procedures have been established as standards. Bariatric surgery has proven effective in the amelioration of metabolic diseases, including type 2 diabetes, hypertension, hyperlipidemia, and cancer. Metabolic operations not focused on weight loss include the partial ileal bypass (PIB) for hyperlipidemia, and vagus nerve stimulation for refractory depression.
Definition of metabolic surgery
In the 1978 book Metabolic Surgery, Drs. Buchwald (co-author of this article) and Varco defined this discipline as “the operative manipulation of a normal organ or organ system to achieve a biological result for a potential health gain.”1 While this statement did not initiate metabolic surgery, it provided language to describe and envision a concept.
Surgery started in prehistory, with the incising of abscesses and closing of surface wounds with thorns, vines, and the contractures of decapitated termites and beetles.2 Elective surgery was introduced around 10,000 BC with trephination of the skull to release evil spirits; by 2,000 BC, the Egyptians and Jews practiced circumcision. Up through the great surgical eras of extirpative and reparative surgery, made feasible by the introduction of anesthesia and antisepsis in the mid-19th century, surgery primarily focused on an organ gone bad.
In contrast, metabolic surgery focuses on altering normal organs to change the body’s neurohormonal milieu. In our exploration of the intertwining of progenitor genes, the influence of the gut microbiota and bile acids, and bioenergetics, we have come to appreciate that most disease processes involve a complex metabolic mosaic of causation. From this perspective has emerged our conviction that metabolic surgery, with its own variegated metabolic processes, can reduce certain imbalances of human affliction.
Historical metabolic surgery landmarks
Possibly the earliest example of metabolic surgery occurred more than 120 years ago, when the reduction of breast cancer metastases was achieved by the extirpation of normal ovaries.3 In addition to endocrine ablations for malignancies, other metabolic procedures became popular in the last century; for example, splenectomy for idiopathic thrombocytopenic purpura, portal diversion for glycogen storage disease, and pancreas transplantation for type 1 diabetes. Probably the most commonly performed metabolic surgery procedure before the introduction of bariatric surgery was surgery for peptic ulcer disease. This procedure involved resecting various segments of normal stomach and dividing branches of normal vagus nerves to cure a distal duodenal ulcer that remained, except for emergencies, untouched by the hand of the surgeon.
Introduced in 1962, with the first human procedure performed in May 1963, the PIB operation for hyperlipidemia is an example of metabolic surgery.4 By interrupting the enterohepatic cholesterol and bile acid cycles, the operation markedly increases fecal steroid excretion, which, in turn, elicits a compensatory increase in cholesterol synthesis and turnover to replenish the body’s cholesterol and bile acids (the primary end-product of cholesterol metabolism).5 With the exception of the rat, all tested animal species, including humans, cannot fully restore their lipid reserves. Consequently, the subject experiences a marked reduction in plasma cholesterol concentration, and the freely and less freely miscible cholesterol pools (including arterial plaque cholesterol deposits) are reduced permanently.5
The Program on the Surgical Control of the Hyperlipidemias (POSCH)—a $65 million, investigator-initiated National Heart, Lung, and Blood Institute National Institutes of Health (NIH)-funded, randomized controlled trial—was the first major study to employ a metabolic surgery procedure, the PIB, as the intervention modality. Published in 1990 in the New England Journal of Medicine, this secondary study of 838 (421 intervention and 417 control) survivors of a single documented myocardial infarction was the first trial to reveal the efficacy of marked cholesterol reduction.6 In addition to a 35 percent reduction in death from coronary heart disease or a confirmed recurrent myocardial infarction, POSCH demonstrated statistically significant reductions in peripheral vascular disease and the need for coronary artery surgery, as well as an increase in life expectancy.7 Part of the POSCH protocol was the serial performance of coronary arteriograms at 0, 3, 5, 7, and 10 years, which showed statistically significant reductions in disease progression and actual plaque regression in the PIB group in comparison to the control group.8 A 25-year POSCH follow-up study revealed the persistence of increased life expectancy in the PIB patients.9
Metabolic bariatric surgery
It is frequently said that bariatric surgery gave rise to metabolic surgery, which is not true. Bariatric surgery is, and always has been, metabolic surgery. To start with, obesity is a disease—a disease of a deranged metabolism.10 Genetics, the neurohormonal-cerebral network, bile acid variability, and the intestinal microbiota all function collectively to establish an individual’s weight set point. Diets can induce weight loss by starving the body’s fat storage, thereby causing the catabolism of reservoir energy for activity and heat. Pharmaceuticals are designed to focus on a single metabolic process to avoid peripheral side effects, but obesity is not due to a single, or even several, metabolic perturbations. Metabolic surgery, on the other hand, is like a shotgun blast of metabolic alterations that favorably affects myriad causal obesity mechanisms.
When bariatric surgery was introduced, the causative mechanisms for the marked weight loss were stated to be restrictive or malabsorptive, in addition to a few anomalous mechanisms, such as electronic gut stimulation.11 However, all restrictive procedures also are malabsorptive and all malabsorptive procedures are restrictive because in their final pathway from the intestine into the circulation of the body, both procedures create caloric deprivation. Also, the weight loss of bariatric surgery generally stops after or before the metabolic set point is reached. To understand the mechanisms of bariatric surgery, we must abandon the simplistic concepts of restrictive and malabsorptive procedures and examine the complex metabolic effects surgery induces.
The intestinal tract is rich in parasympathetic and sympathetic innervation. In fact, 90 percent of the vagal nerve is afferent and carries messages from the gut to the brain, particularly to the hypothalamus.12 The sympathetic nerve supply to the gut is primarily mediated via the celiac access and is intimately involved in glucose production and release.13 In addition to these communicating networks to and from cerebral centers, a dense intrinsic nerve syncytium resides in the submucosa of the intestine from esophagus to anus,14 and a recognized gastric fundus pacemaker regulates gastric wave contractions and synchronization of gastric function.15 These neural networks surely must be involved in modulating eating behavior, food selection, and nutrient metabolism. Every one of our metabolic/bariatric operations divides, excises, transposes, or stimulates these regulatory pathways.
Most of the literature on metabolic/bariatric surgery causative mechanisms has been devoted to analysis of certain of the approximately 100 gut hormones that have been so far described, in particular glucagon-like peptide 1, peptide YY, gastric inhibitory polypeptide, and ghrelin,16-19 as well as the adipocyte-derived hormone leptin.20 This hormonal mosaic interacts with the neuro-cerebral network in establishing the bases for obesity, as well as the mitigating effects of metabolic/bariatric surgery. Other mechanisms of causation and therapy have, and will continue to, come to the forefront (for example, bile acids and their qualitative and quantitative alterations and the constituency of the intestinal microbiome).21-23
Progression of bariatric operations
More than 50 operations have been proposed and implemented for the management of morbid obesity, a testament to the vigor and imagination of its advocates.24 The first nonresectional bariatric surgery procedure was performed by Richard L. Varco, MD, PhD, FACS, in 1953. The operation was a jejunoileal bypass (JIB) with an end-to-end jejunoileostomy and separate drainage of the bypassed bowel to the cecum.25 Varco never published the case, but this procedure was subsequently reported by Kremen, Linner, and Nelson in 1954.26 Several JIB modifications followed, the most popular being the “14 to 4” end-to-side reconstruction reported by Payne and DeWind.27
Though highly effective, the JIB was associated with many complications and gave way to the gastric bypass, first introduced by Mason and Ito in 1966.28 This procedure was modified to a stapled, undivided separation of the upper and lower pouch, with drainage of the upper pouch by a loop gastrojejunostomy, by Alden in 1977.29 In the same year, Griffen et al and Pories et al reported the first gastric bypass with a Roux-en-Y gastrojejunostomy (RYGB) (see Figure 1).30,31 At present, a variation of a single anastomosis loop gastrojejunostomy is again finding favor.32
Figure 1. Roux-en-Y gastric bypass
Buchwald H. Chapter 9: Vertical banded gastroplasty*
Mason, always eager to simplify bariatric procedures and minimize their side-effects and complications, next introduced gastroplasty.33 Two variants of the vertical banded gastroplasty (VBG) with a restricted vertical pouch held favor, and in the 1990s eclipsed the RYGB in the numbers of procedures performed; those with distal restriction by a Silastic ring (see Figure 2) and those with a Marlex band outlet restrictor.34,35 By the turn of the century, however, the VBG faded into near oblivion because of fairly ubiquitous weight regain and gastroesophageal reflux over time.
Figure 2. Vertical banded gastroplasty
Buchwald H. Chapter 9: Vertical banded gastroplasty*
Scopinaro returned to the intestinal bypass concept in the late 1970s but sought to avoid the static intestinal loop toxic effects of the original procedure by performing a subtotal gastrectomy with Roux limb drainage, at least 250 cm in length, anastomosed to a long biliopancreatic limb to form a common channel of 50 cm (see Figure 3).36 The Scopinaro procedure, when it crossed the Atlantic, was transformed into the duodenal switch (DS), first by Picard Marceau, MD, PhD, FACS, FRCSC, who performed a vertical sleeve gastrectomy with cross-stapling of the duodenum and an approximately 100-cm common channel.37 Cross-stapling of the duodenum proved to be unstable and led to the modern biliopancreatic diversion/duodenal switch (BPD/DS), or simply the DS, by Hess and Hess in 1994, who divided the duodenum and performed a proximal duodenoileostomy (see Figure 4).38 Of the bariatric procedures, the BPD and the DS provide the greatest weight loss, are the most enduring in their weight response, and have the highest rate of comorbidity resolution, especially for type 2 diabetes. Nevertheless, they are relatively infrequently performed because they are difficult procedures necessitating a highly skilled surgeon, and because they can cause long-term nutritional and hepatic complications requiring dedicated lifelong follow-up by the practitioner or another bariatric specialist.
Figure 3. Biliopancreatic diversion
Buchwald H. Chapter 3: Biliopancreatic diversion*
Figure 4. Duodenal switch
Buchwald H. Chapter 4: Duodenal switch*
The DS gave birth to the sleeve gastrectomy (SG) after an interlude of failed enthusiasm for the most purely anatomically restrictive procedure, the adjustable gastric band (AGB). The earlier nonadjustable GB originated from three surgical groups: Wilkinson and Peloso, Kolle, and Molina and Oria, and was followed by the AGB concept initiated by Kuzmak.39-42 Complications of band slippage and gastric perforation, as well as failure to maintain weight loss, led to the decline and essential disappearance of the AGB.
In 2017, the SG became the most frequently performed metabolic/bariatric operation in the world (see Figure 5).43 First advocated by Regan and colleagues in 2004, Gagner popularized it as the first stage of a DS.44-45 Gagner and others soon recognized that the freestanding SG for some patients was definitive and required no second-stage revision to a DS, though a second operation with conversion to a DS or a RYGB is feasible. This procedure is attractive because it is technically straightforward and can be performed rapidly without an anastomosis. Yet, a significant incidence of upper-gastric staple-line leaks is associated with this procedure. The desire to avoid such leaks led to the introduction of gastric imbrication, without resection.46
Figure 5. Sleeve gastrectomy
Buchwald H. Chapter 10: Sleeve gastrectomy*
Innovations proposed and tested in metabolic/bariatric surgery are ongoing and increasing in frequency. Among others under scrutiny are electrode gastric stimulation, electrode vagal nerve blockage, single-anastomosis loop RYGB, single anastomosis variation of DS, banded SG, and banded RYGB.47-52 The safety and effectiveness of banded RYGB has been verified by a systematic review and meta-analysis.53 In addition, several endoscopic suggestions for narrowing the gastric lumen by internal imbrication have been offered. Mention also should be made of endoscopically inserted gastric balloons, which work as gastric bezoars to decrease appetite and increase satiety but are approved only for temporary management.54
Other metabolic surgery procedures
The observation that weight-loss bariatric procedures ameliorated and possibly cured type 2 diabetes was made in the late 1990s by the groups of Pories, Scopinaro, and Cowan, followed to date by more than 4,000 papers on this subject since 2000.55-57 In 2004, Buchwald et al published the first meta-analysis on the response of the obesity comorbidities to metabolic/bariatric surgery, followed by a meta-analysis dedicated to the effect of metabolic/bariatric procedures solely on type 2 diabetes.58,59 These studies showed an 86 percent reduction or improvement of type 2 diabetes.
Next came studies of the success of traditional bariatric operations in patients with type 2 diabetes who were not morbidly obese, best illustrated in a meta-analysis of 11 randomized controlled trials by Cummings and Cohen.60 Reluctant recognition of the significance of these data was provided in 2016 in a joint statement advocating metabolic surgery in the treatment algorithm for type 2 diabetes by an international diabetes conclave that included the leading nonsurgical diabetes organizations.61
Progression of thought promoted the exploration of non-weight-loss metabolic surgery for type 2 diabetes, including: omentectomy, electrode stimulation of the stomach and duodenum, vagal blockade, duodenal-jejunal bypass, entroluminal duodenal bypass, hydrothermal duodenal mucosal ablation, and ileal transposition, as well as extragastric/intestinal operations of pancreas and islet cell transplantation, and, most intriguingly, transcatheter perirenal neuroablation.62 Recently, a retrospective review of the POSCH study demonstrated that the PIB prevents the onset of type 2 diabetes,63 which initiated a clinical trial of the ability of the PIB to mitigate existing type 2 diabetes.
Metabolic/bariatric surgery lowers the incidence of mortality of several cancers.64 Carotid body surgery, as well as perirenal neuroablation for hypertension, are metabolic procedures. Specific metabolic surgery recommendations to treat mental illnesses, distinguished from diffuse electrode shock therapy, may have a promising future. At present, this field is exploring single cervical vagus nerve stimulation and subgenual cingulate gyrus brain stimulation in the brain for refractory depression.65,66
Translational surgery is cyclical and cognitive
The traditional concept of translational surgery is that of a linear progression from hypothesis to computer modeling to bench and/or animal testing, and, finally, to clinical trial. Science, in particular in the field of metabolic surgery, does not stop there, with or without translation to clinical application, but returns to the laboratory. Clinical knowledge gained prompts the next experiment toward future progress.
Our expanding surgical technologies open new vistas, but they should not be mistaken for intellectual growth. We need ongoing original thought and disciplined scientific exploration of the manner in which metabolic surgery can influence the underlying mechanisms responsible for the healthy functioning of the body.
This work was supported by the ACS. The authors declare that they have no relevant conflict of interest.
We are grateful to the ACS for its generous sponsorship of the Metabolic Surgery Symposium and associated journal publication development. We thank Jane N. Buchwald, chief scientific research writer, Medwrite Medical Communications, WI, for manuscript editing and publication coordination. And we thank Patrick Beebe and Donna Coulombe, ACS Executive Services, for their expert organization of the Metabolic Surgery Symposium.
*Source: Buchwald’s Atlas of Metabolic & Bariatric Surgical Techniques and Procedures. New York, NY: Elsevier; 2011. (Reprinted with permission from the author and Elsevier, Inc.)
- Buchwald H, Varco RL. Metabolic Surgery. New York: Grune & Stratton; 1978.
- Haeger K. The Illustrated History of Surgery. New York: Bell Publishing; 1988.
- Boyd S. On oophorectomy in the treatment of cancer. Br Med J. 1897;2(1918):890-896.
- Buchwald H. Lowering of cholesterol absorption and blood levels by ileal exclusion: Experimental basis and preliminary report. 1964;29(5):713-720.
- Moore RB, Frantz ID Jr., Buchwald H. Changes in cholesterol pool size, turnover rate, and fecal bile acid and sterol excretion after partial ileal bypass in hypercholesterolemic patients. Surgery. 1969;65(1):98-108.
- Buchwald H, Varco RL, Matts JP, et al. Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH). N Engl J Med. 1990;323(14):946-955.
- Buchwald H, Varco RL, Boen JR, et al. Effective modification by partial ileal bypass reduced long-term coronary heart disease, mortality, and morbidity: Five-year post-trial follow-up report from the POSCH. Arch Intern Med. 1998;158(11):1253-1261.
- Buchwald H, Matts JP, Fitch LL, et al. Changes in sequential coronary arteriograms and subsequent coronary events. JAMA. 1992;268(11):1429-1433.
- Buchwald H, Rudser KD, Williams SE, Michalek VN, Vagasky J, Connett JE. Overall mortality, incremental life expectancy, and cause of death at 25 years in the Program on the Surgical Control of the Hyperlipidemias (POSCH). Ann Surg. 2010;251(6):1034-1040.
- American Medical Association Resolution 420 (A13): Recognition of Obesity as a Disease, 05/16/2013. Available at: www.npr.org/documents/2013/jun/ama-resolution-obesity.pdf. Accessed November 26, 2018.
- Buchwald H, Buchwald JN. Evolution of operative procedures for the management of morbid obesity: 1950–2000. Obes Surg. 2002;12(5):705-717.
- Berthoud HR. The vagus nerve, food intake, and obesity. Regul Pept. 2008;149(1):15-25.
- Zheng J, DiLorenzo DJ, McLaughlin L, Roberts AT, Greenway FL. Stimulation of sympathetic innervation in the upper gastrointestinal tract as a treatment for obesity. Med Hypotheses. 2009;72(6):706-710.
- Bornstein JC, Furness JB. Correlated electrophysiological and histochemical studies of submucous neurons and their contribution to understanding enteric neural circuits. J Auton Nerv Syst.1988;25(1):1-13.
- Patrick A, Epstein O. Review article: Gastroparesis. Aliment Pharmacol Ther. 2008;27(9):724-740.
- Buchwald H, Menchaca HJ, Michalek VN, Bertin NT. Ileal effect on blood glucose, HbA1C, and GLP-1 in Goto-Kakizaki rats. Obes Surg. 2014;24(11):1954-1960.
- Batterham RL, Ffytche DH, Rosenthal JM, et al. PYY modulation of cortical and hypothalamic brain areas predicts feeding behaviour in humans. Nature. 2007;450(7166):106-109.
- Lauritsen KB, Christensen KC, Stokholm KH. Gastric inhibitory polypeptide (GIP) release and incretin effect after oral glucose in obesity and after jejunoileal bypass. Scand J Gastroenterol. 1980;15(4):489-495.
- Le Roux CW, Patterson M, Vincent RP, Hunt C, Ghatei MA, Bloom SR. Postprandial plasma ghrelin is suppressed proportional to meal calorie content in normal-weight but not obese subjects. J Clin Endocrinol Metab. 2005;90(2):1068-1071.
- Saad MF, Riad-Gabriel MG, Khan A, et al. Diurnal and ultradian rhythmicity of plasma leptin: Effects of gender and adiposity. J Clin Endocrinol Metab. 1998;83(2):453-459.
- Fiorucci S, Distrutti E. Bile acid-activated receptors, intestinal microbiota, and the treatment of metabolic disorders. Trends Mol Med. 2015;21(11):702-714.
- Furet JP, Kong LC, Tap J, et al. Differential adaptation of human gut microbiota to bariatric surgery-induced weight loss: Links with metabolic and low-grade inflammation markers. Diabetes. 2010;59(12):3049-3057.
- Zhang H, DiBaise JK, Zuccolo A, et al. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci USA. 2009;106(7):2365-2370.
- Buchwald H. The evolution of metabolic/bariatric surgery. Obes Surg. 2014;24(8);1126-1135.
- Buchwald H, Rucker R. 1987. The rise and fall of jejunoileal bypass. In: Nelson RL, Nyhus LM, eds. Surgery of the small intestine. Norwalk, CT: Appleton Century Crofts; 529-541.
- Kremen AJ, Linner LH, Nelson CH. An experimental evaluation of the nutritional importance of proximal and distal small intestine. Ann Surg. 1954;140(3):439-447.
- Payne JH, DeWind LT. Surgical treatment of obesity. Am J Surg. 1969;118(2):141-147.
- Mason EE, Ito C. Gastric bypass in obesity. Surg Clin North Am. 1967;47(6):1345-1351.
- Alden JF. Gastric and jejunoileal bypass: A comparison in the treatment of morbid obesity. Arch Surg. 1977;112(7):799-806.
- Griffen WO, Young VL, Stevenson CC. A prospective comparison of gastric and jejunoileal bypass operation for morbid obesity. Ann Surg. 1977;186(4):500-509.
- Liscia G, Scaringi S, Facchiano E, Quartararo G, Lucchese M. The role of drainage after Roux-en-Y gastric bypass for morbid obesity: A systematic review. Surg Obes Relat Dis. 2014;10(1):171-176.
- Rutledge R. The mini-gastric bypass: Experience with the first 1,274 cases. Obes Surg. 2001;11(3):276-280.
- Printen KJ, Mason EE. Gastric surgery for relief of morbid obesity. Arch Surg. 1973;106(4):428-431.
- Laws HL, Piantadosi S. Superior gastric reduction procedure for morbid obesity: A prospective, randomized trial. Am J Surg. 1981;193(3):334-336.
- Mason EE. Vertical banded gastroplasty. Arch Surg. 1982;117(5):701-706.
- Scopinaro N, Gianetta E, Civalleri D, Bonalumi U, Bachi V. Biliopancreatic bypass for obesity: II. Initial experiences in man. Br J Surg. 1979;66(9):618-620.
- Marceau P, Biron S, Bourque RA, Potvin M, Hould FS, Simard S. Biliopancreatic diversion with a new type of gastrectomy. Obes Surg. 1993;3(1):29-35.
- Hess DW, Hess DS. Laparoscopic vertical banded gastroplasty with complete transection of the staple line. Obes Surg. 1994;4(1):44-46.
- Wilkinson LH, Peloso OA. Gastric (reservoir) reduction for morbid obesity. Arch Surg. 1981;116(5):602-605.
- Kolle K. Gastric banding. OMGI 7th Congress, Stockholm, Sweden. 1982;37(abstr 145).
- Molina M, Oria HE. Gastric segmentation: A new, safe, effective, simple, readily revised and fully reversible surgical procedure for the correction of morbid obesity. 6th Bariatric Surgery Colloquium, Iowa City. June 3, 1983;15(abstr).
- Kuzmak LI. Silicone gastric banding: A simple and effective operation for morbid obesity. Contemp Surg. 1986;28(1):13-18.
- Angrisani L, Santonicola A, Iovino A, et al. Bariatric surgery and endoluminal procedures: IFSO worldwide survey 2014. Obes Surg. 2017;27(9):2279-2289.
- Regan JP, Inabnet WB, Gagner M, Pomp A. Early experience with two-stage laparoscopic Roux-en-Y gastric bypass as an alternative in the super-super obese patient. Obes Surg. 2003;13(6):861-864.
- Gagner M, Deitel M, Kalberer TL, Erickson AL, Crosby RD. The Second International Consensus Summit for Sleeve Gastrectomy, March 19–21, 2009. Surg Obes Relat Dis. 2009;5(4):476-485.
- Doležalová-Kormanová K, Buchwald JN, Skochova D, et al. Five-year outcomes: Laparoscopic greater curvature plication for treatment of morbid obesity. Obes Surg. 2017;27(11):2818-2828.
- Cigaina V. Gastric pacing as therapy for morbid obesity: Preliminary results. Obes Surg. 2002;12(Suppl 1):12S-16S.
- Shikora SA, Wolfe BM, Apovian CM, et al. Sustained weight loss with vagal nerve blockade but not with sham: 18-month results of the ReCharge Trial. J Obes. 2015;Article ID 365604:1-8.
- Chevallier JM, Arman GA, Guenzi M, et al. One thousand single anastomosis (omega loop) gastric bypass to treat morbid obesity in a 7-year period: Outcomes show few complications and good efficacy. Obes Surg. 2015;25(6):951-958.
- Sanchez-Pernaute A, Rubio MA, Perez Aguirre E, Barabash A, Cabrerizo L, Torres A. Single-anastomosis duodenoileal bypass with sleeve gastrectomy: Metabolic improvement and weight loss in first 100 patients. Surg Obes Relat Dis. 2013;9(5):731-735.
- Tognoni V, Benavoli D, Bianciardi E, et al. Laparoscopic sleeve gastrectomy versus laparoscopic banded sleeve gastrectomy: First prospective pilot randomized study. Gastroenterol Res Pract. 2016;Article ID 6419603:1-5.
- Fobi M, Lee H, Fleming AW. The surgical technique of the banded gastric bypass. J Obes & Weight Regulation. 1989;8:99-102.
- Buchwald H, Buchwald JN, McGlennon TW. Systematic review and meta-analysis of medium-term outcomes after banded Roux-en-Y gastric bypass. Obes Surg. 2014;24(9):1536-1551.
- Kumar N. Endoscopic therapy for weight loss: Gastroplasty, duodenal sleeves, intragastric balloons, and aspiration. World J Gastrointest Endosc. 2015;7(9):847-859.
- Pories WJ, Swanson MS, MacDonald KG, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg. 1995;222(3):339-350.
- Scopinaro N, Adami GF, Marinari GM, et al. Biliopancreatic diversion. World J Surg. 1998;22(9):936-946.
- Cowan GS Jr., Buffington CK. Significant changes in blood pressure, glucose, and lipids with gastric bypass surgery. World J Surg. 1998;22(9):987-992.
- Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: A systematic review and meta-analysis. JAMA. 2004;292(14):1724-1737.
- Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: Systematic review and meta-analysis. Am J Med. 2009;122(3):248-256.
- Cummings DE, Cohen RV. Bariatric/metabolic surgery to treat type 2 diabetes in patients with a BMI <35 kg/m2. Diabetes Care. 2016;39(6):924-933.
- Rubino F, Nathan DM, Eckel RH, et al. Delegates of the 2nd Diabetes Surgery Summit. Metabolic surgery in the treatment algorithm for type 2 diabetes: A joint statement by international diabetes organizations. Diabetes Care. 2016;39(6):861-877.
- Mahfoud F, Schlaich M, Kindermann I, et al. Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension: A pilot study. Circulation. 2011;123(18):1940-1946.
- Buchwald H, Oien DM, Schieber DJ, Bantle JP, Connet JE. Partial ileal bypass affords protection from onset of type 2 diabetes. Surg Obes Relat Dis. 2017;13(1):45-51.
- Adams TD, Stroup AM, Gress RE, et al. Cancer incidence and mortality after gastric bypass surgery. Obesity (Silver Spring). 2009;17(4):796-802.
- Yuan W, Williams BN. Long-term vagus nerve stimulation for severe refractory depression: A case study with a six-year follow-up. J Neuropsychiatry Clin Neurosci. 2012;24(4):E50-1.
- Mayberg H, Lozano A, Voon V, et al. Deep brain stimulation for treatment-resistant depression. J Neuron.