Recent advancements in bariatric/metabolic surgery

Abstract Obesity and type 2 diabetes mellitus (T2DM) are currently two pan‐endemic health problems worldwide and are associated with considerable increase in morbidity and mortality. Both diseases are closely related and very difficult to control by current medical treatment, including diet, drug therapy and behavioral modification. Bariatric surgery has proven successful in treating not just obesity but also in significantly decreasing overall obesity‐associated morbidities as well as improving quality of life in severely obese patients (body mass index [BMI] >35 kg/m2). A rapid increase in bariatric surgery started in the 2000s when the laparoscopic surgical technique was introduced into this field. Many new procedures had been developed and changed the face of modern bariatric surgery. Recently, bariatric surgery played as gastrointestinal metabolic surgery has been proposed as a new treatment modality for obesity‐related T2DM for patients with BMI >35 kg/m2. Strong evidence has demonstrated that bariatric/metabolic surgery is an effective and durable treatment for obese T2DM patients. Bariatric/metabolic surgery is now becoming an important surgical division. The present article examines and discusses recent advancements in bariatric/metabolic surgery and covers four major fields: (i) the rapid increase in numbers and better safety; (ii) new procedures with better outcomes; (iii) from bariatric to metabolic surgery; and (iv) understanding the mechanisms and personalized treatment.

reduction surgery, has been shown as not only an effective treatment for severe obesity (BMI >35 kg/m 2 ) but has also resulted in marked improvement of T2D control. 9,10 Encouraged by the success of bariatric surgery, gastrointestinal metabolic surgery has been recently proposed as a new treatment modality for obesity-related T2DM in patients with BMI <35 kg/m 2.8, 11 Rapid development of bariatric/metabolic surgery for the treatment of obesity and T2DM has occurred in recent decades, although bariatric surgery has been introduced for more than 60 years. The present review summarizes recent advancements in bariatric/metabolic surgery and will build a foundation for updates in bariatric/metabolic surgery and for the development of further clinical trials to provide more evidence in this field for the treatment of obesity as well as T2DM.  [13][14][15][16][17] Owing to the high incidence of obesity, the bariatric procedure has become the most commonly carried out surgical procedure in the USA. 18 However, it is interesting to see that the growth rate was higher in Asia than in other parts of the worldwide (Figure 1). In viewing the T2DM epidemic in Asia, bariatric/metabolic surgery will soon be a very important surgical division.
Although bariatric surgery, especially carried out by laparoscopic surgery, is one of the most common complex laparoscopic operations, the safety of laparoscopic bariatric surgery has improved very rapidly. The 30-day operation mortality was reported to be 2% in 2004 and decreased to 0.2% in 2009 through the high-quality bariatric center program in the USA. 19,20 Well-experienced surgeons, fully trained in laparoscopic techniques and proctorship, teamwork and adequate volume are important for a high-quality bariatric surgical center. 21 Improvements in technology, operative techniques, results of clinical trials and accumulation of experience all contributed to this progress. 22 In the most recent publication, the 30-day mortality from the European center of excellence program was reported to be only 0.012%. 23 In conclusion, bariatric/metabolic surgery has had a 10-fold growth in the past decade but the operation is 100-fold safer now.

| NEW PROCEDURES WITH BE TTER OUTCOMES
Bariatric surgery has been evolving over the past 60 years and has undergone a significant increase in volume since the advent of laparoscopic surgery. However, the procedure of bariatric surgery is still evolving and numerous procedures with a plethora of variations are presently advocated as a method of choice to treat morbid obesity. Intestinal bypass and VBG have been abandoned and LAGB is severely decreasing. 12 There has been a dramatic change in bariatric/metabolic procedures in the past decade. The most impressive change in bariatric procedure is the advent of laparoscopic sleeve gastrectomy (LSG). There is no reported case of LSG in the 2003 IFSO report. 14 However, since 2014, LSG has become the leading bariatric procedure in the USA. 24 Figure 2 shows the change of bariatric procedures in the USA from 2011 to 2015. According to the statistics of IFSO, the most commonly carried out procedure worldwide in 2011 was Roux-en-Y gastric bypass RYGB (45%), followed by LSG (37%) and LAGB (10%). 16 Other procedures, such as laparoscopic single anastomosis (Mini-) gastric bypass (LSAGB) and biliopancreatic diversion/duodenal switch (BPD/DS) comprise approximately 1.5% and 2.2%, respectively. Some of the commonly carried out procedures are introduced as follows.

| Laparoscopic sleeve gastrectomy
Sleeve gastrectomy (SG) was first described as a first step as part of BPD/DS for obesity by Dr Doug Hess in March 1988. 25 In the development of laparoscopic BPD/DS, Dr Gagner used LSG as a first-stage bariatric procedure for high-risk patients in order to reduce the risk profile of patients, and later carried out a F I G U R E 1 Total number of bariatric surgeries worldwide and in the Asia-Pacific region according to statistics from International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) [13][14][15][16][17] second-stage operation once adequate weight loss was achieved. 26 However, it was noted that LSG alone could cause good weight loss before the second procedure. 27 By removing approximately 75% of the stomach from the greater curvature side and leaving a long narrow gastric tube and antrum, LSG not only restricts food intake but also increases both gastric emptying and intestinal transit time. As a result of its effectiveness in weight loss, relative simplicity, and fewer long-term nutritional problems, LSG has very rapidly now become the most commonly carried out bariatric/metabolic surgery worldwide. 16,24 LSG is especially welcomed by Asian surgeons for its advantages of avoidance of remnant gastric cancer. 28 Laparoscopic sleeve gastrectomy was found to have a more durable and greater weight loss effect than other restrictive-type operations such as VBG or LAGB. 29 Total weight loss of approximately 25-30% and excess weight loss of 60-70% for up to 10 years can be achieved. 30,31 However, a significant drawback of this procedure is the development of reflux esophagitis. Up to 30% of LSG patients may require revision surgery for reflux esophagitis or weight regain. [29][30][31][32] Table 1 shows long-term weight loss (>10 years) in different bariatric procedures.

| Laparoscopic R-Y gastric bypass
Five-decades-old gastric bypass surgery has become a time-honored procedure and is currently regarded as a standard bariatric/metabolic procedure. Following the introduction of the laparoscopic era, laparoscopic R-Y gastric bypass (LRYGB) has accelerated the development of both bariatric and metabolic surgery. 44 Long-term (>10 years) weight loss after RYGB was reported to be around 25-30% total weight loss and 55-70% excess weight loss (EWL). [33][34][35][36][37][38] Up to 20% of RYGB patients may require revision surgery for various complications or weight regain. Weight regain after LRYGB was related to dilatation of the gastric pouch and anastomosis. [45][46] Endoscopic treatment was developed recently and is recommended for first-line treatment for those with weight regain after RYGB. [47][48] Weight loss after LRYGB was found to be similar or slightly better than with LSG but with more nutritional deficiencies in LRYGB. [49][50][51] Hence, LSG is now becoming the leading bariatric/metabolic procedure instead of LRYGB.

| Laparoscopic single anastomosis (Mini-) gastric bypass
A simplified single anastomosis gastric bypass, LSAGB or Mini-Gastric Bypass, was first reported by Rutledge in 2001. 52 Although some controversy concerning the procedure existed in the USA, one randomized study confirmed it is a simpler and safer procedure compared to LRYGB. 53 Many other reports of large series confirmed the safety and long-term efficacy of this procedure. 54-57 LSAGB can also be used in revision surgery for failed restrictive-type procedures with good results. [58][59] Long-term (>10 years) weight loss after LSAGB was reported to be around 30% total weight loss and 70-75% EWL. 34,52 However, this procedure has an increased risk of malnutrition because the bypass limb is longer than in RYGB. 34,52 Up to 5% of LSAGB patients may require a revision surgery for malnutrition, weight regain and complications. 60

| New procedures
Many new bariatric/metabolic surgeries have been introduced in the past decade. However, most of the procedures were experimental, and there is lack of evidence and long-term data. The most interesting procedure was duodenojejunal bypass (DJB), which was inspired by Rubino's animal experiment for the treatment of T2DM. 64 However, simple exclusion of the duodenum was found to be less effective than conventional bariatric/metabolic surgery. 65 Therefore, duodenojejunal bypass with sleeve gastrectomy (DJB-SG) has recently been introduced from Asia as a novel metabolic surgery by adding a duodenal switch procedure to SG, which combines the principles and advantages of sleeve gastrectomy and duodenal switch. 66 The efficacy of DJB-SG was similar to conventional gastric bypass. 28 The major advantage of DJB-SG compared to RYGB is avoidance of the risk of gastric cancer arising from the remnant stomach by leaving no excluded stomach. Other theoretical advantage of DJB-SG is related to preservation of the pylorus, which includes prevention of dumping syndrome and facilitating iron, calcium, vitamin B12 and protein absorption by preserving the acid and intrinsic factor. 67 A recent study showed that by adding a duodenal exclusion to SG, DJB-SG can increase weight loss by more than 10% and improve glycemic control as well as reduce uric acid level. 68 This finding further supported the important role of duodenum exclusion in the treatment of T2DM. A five-year report was published recently from Japan to support the efficacy of this procedure. 69 Another interesting new procedure was single anastomosis duodeno-ileostomy (SADI), a simplified BPD/DS using a loop anastomosis replacing the RY anastomosis of the duodenal switch. 70 Similar modification was laparoscopic single anastomosis for DJB (LSADJB-SG). 28 Both procedures are a simplified version of the original operation by replacing the RY reconstruction by loop anastomosis, as is SAGB to RYGB.
Other novel procedures, such as LSG with ileal transportation, 71 LSG with proximal jejunal bypass, 72 LSG with bi-partition, 73 laparoscopic greater curvature side gastric plication, 74,75 banded gastric plication 76 and Nissen fundoplication with gastric placation 77 were either too complicated or without enough evidence to be supported in clinical use.
However, there is a trend of moving from laparoscopic bariatric/ metabolic surgery to endoscopic procedures. 78 Most commonly carried out endoscopic procedure was intragastric balloon. 79 89 The first randomized controlled trial (RCT) in the world specific to metabolic surgery for the treatment of T2DM was from Asia. 90 This study compared LSG to gastric bypass (LSAGB) for the treatment of T2DM in Asian patients with BMI <35 kg/m 2 and was the first study to prove that gastric bypass (a duodenum exclusion procedure) had better efficacy on T2DM remission than LSG (non-duodenum exclusion procedure). Following this landmark study, many RCT focusing on the comparison of metabolic surgery and medical treatment for the treatment of T2DM have been carried out and universally showed that metabolic surgery is more effective than medical treatment in glycemic control. [91][92][93][94][95][96][97][98][99] Table 2  The potential benefits of metabolic surgery to prevent mortality and end-organ damage may only be confirmed by large multicenter trials with long-term follow up.

| UNDERSTANDING TH E MECHANISM
One of the major advancements in bariatric/metabolic surgery is understanding the mechanism. Bariatric/metabolic surgery is a gastrointestinal surgery and its effect is through various gastrointestinal anatomical changes and reroute. 100 Updated theory of mechanism is summarized below.

| Gastric restriction
Procedures without gastric restriction, such as intestinal bypass or duodenal bypass, can produce only a minimal weight loss. 101 VBG was the first successful bariatric procedure with a pure gastric restriction effect. LAGB is another pure gastric restrictive procedure. Both procedures can provide an average of approximately 15% total weight loss in the long term, but many patients require revision for weight regain.
The gastric restrictive effect of gastric bypass was provided by a small gastric pouch and small gastrojejunal anastomosis. Weight regain after gastric bypass was commonly attributed to dilated gastric pouch and wide anastomosis. 40,41 Proposed management of weight regain after gastric bypass was resizing the gastric pouch or endoscopic downsizing of the gastrojejunostomy. 42,43 Therefore, gastric restrictive effect was considered to be the most important part of metabolic surgery and comprised about 70% of the effect of gastric bypass. 17   exclude the duodenum and proximal jejunum without gastric restriction, and improved glycemic control without reduction of food intake and weight loss. 65 A recently developed new device, duodenum jejunal sleeve liner, also had a similar effect to DJB. 80

| Rapid delivery of food or short common channel
Rerouting the GI tract by gastric bypass not only excludes the duodenum but may rapidly deliver incompletely digested food to the distal bowel which may induce a strong gut hormone change, mainly peptide tyrosine tyrosine (PYY) and glucagon-like peptide 1 (GLP-1).
Interestingly, sleeve gastrectomy was found to have this effect without rerouting the GI tract possibly as a result of rapid intestine transit time. 104

| Gut microbiota environment and bile acid metabolism
Obese patients were found to have different microbiota that can be changed after bariatric surgery. 105 In addition, microbiota transfer from lean mice has a weight-reducing effect on obese mice. 106 However, a more important mechanism than microbiota was the finding of bile acid mechanism. Serum bile acid was found to increase after bypass surgery but not in LAGB, and the increase was correlated with weight loss. 107 Recent experiments on gene kick-out mice demonstrated that bile acid, not GLP-1, was the key player in SG. 108 Therefore, bile acid, through the nuclear farnesoid X receptor (FXR) in liver and small intestine, may play very important roles in weight reduction and T2DM remission. 109 In conclusion, the underlying mechanism for bariatric/metabolic surgery is intriguing and many theories were recently proposed but none of these theories necessarily precludes the others. Further studies are mandatory to elucidate the mechanism of bariatric/metabolic surgery. Through this knowledge, new treatment modality or novel medicine may thus be developed.  113 To combine these important predictors, a scoring system consisting of four variables: age, BMI, C-peptide level and duration of diabetes has been developed. 114 This ABCD Diabetes Surgery Score system is especially designed for predicting the success of metabolic surgery and has been validated in many studies. [115][116][117] In clinical practice, this