Duodenal Exclusion: Indications and Clinical Considerations

Abstract

Duodenal exclusion is used in surgery for multiple reasons. It can be used to treat primary pathology, such as with peptic ulcer disease, malignancy, gastric outlet obstruction, or after trauma. It is also used in metabolic surgery to add a hypoabsorptive effect for weight loss and beneficial impact on various co-morbidities. There are additional neurohormonal implications of duodenal exclusion that vary, depending on where the intestine is divided, and how long of a common channel or absorptive limb is left in place. Impact on diseases such as diabetes is mediated via complex pathways that continue to be researched today. Duodenal exclusion exhibits indisputable benefits but is linked to well-known side effects and complications. Understanding the physiological importance of the duodenum, the implications of its exclusion, the variety of methods for reconstruction and their impact is important in caring for these patients after surgery.

1. Introduction

Obesity has become a major public health problem with an undeniable impact on overall well-being and survival given its association with multiple diseases such as diabetes mellitus, cardiovascular disease, and various malignancies among others [1, 2]. Bariatric, or metabolic surgery, is the most effective current treatment for obesity, resulting not only in significant weight reduction but also significant improvement and even remission of several of these comorbidities [3, 4]. It has been shown that these benefits are related to both, the anatomical rearrangement, and the changes in gut physiology. Each segment of the gastrointestinal tract has a different influence on the metabolic pathways; thus, clinical outcomes differ among the divergent surgical procedures. When duodenal exclusion (DE) is performed, caloric restriction, diversion of the proximal small bowel, changes in nutrient absorption, and effects on gastrointestinal tract hormones are underlying mechanisms that lead to such favorable results. The contribution of each of these factors to weight reduction and metabolic amelioration varies according to the type of surgery. Since diabetes mellitus along with obesity has become one of the leading health problems worldwide, the process for the favorable effects of this group of procedures in the mitigation of hyperglycemia and even resolution of diabetes mellitus type 2 (T2DM), has been widely studied. Changes in bile acid circulation and metabolism, incretins and possible anti-incretins, gastrointestinal nutrient-sensing and metabolization, glucose and energy homeostasis, as well as mediators of the intestinal microbiome, are all weight-independent factors believed to be related to these antidiabetic outcomes. However, although the beneficial effects regarding weight loss and metabolic improvement, the gastric acid reduction and/or hypoabsorption associated with surgeries involving DE led to significant nutrient deficiency and, if not treated, long-term complications.

2. Physiological role of the duodenum

The duodenum is a horseshoe-shaped structure and the first and shortest segment of the small intestine. It is a place of important enzymatic release and where the gastric secretions, bile, and different digestive enzymes from the gallbladder and pancreatic gland merge together. These features make the duodenum play a major role in the regulation of digestion, absorption of nutrients, and gastrointestinal tract motility [5]. One of the main functions is to alkalinize the lumen secretions thus preventing mucosal damage [6, 7]. The duodenum has the luminal capacity to sense the acidic environment generated by the gastric secretions and responds with different coordinated mechanisms that include the efflux of bicarbonate (HCO3-) to stabilize the pH, an increased mucus production by goblet cells and Brunner glands, neuronal activation, and an improvement in the ON-mediated vasodilation consequently enhancing blood flow. The duodenum is also involved in the absorption of calcium and iron [8, 9]. It is the primary site for calcium active transport mediated by vitamin D and absorbs practically all iron from both, heme and nonheme sources being a key element in iron homeostasis and cellular proliferation. This segment of the small bowel is the first site of interaction between the food products and the biliary and pancreatic secretions where the initial steps regarding digestion, hydrolysis, and absorption take place [10]. Proteins, whose digestion starts in the stomach, are finally cleaved and, most of them, absorbed in the duodenum. This process is favored by the pancreatic zymogen trypsinogen, which is converted into trypsin by the duodenal endopeptidase and activates all the other pancreatic zymogens that mediate proteolysis. Lipids on the other hand, after reaching the duodenum, stimulate the secretion of cholecystokinin (CCK), which encourages the release of the pancreatic lipase that conducts their hydrolysis. Moreover, the duodenum produces a variety of gastrointestinal hormones that also play a fundamental role in the digestion and absorption of nutrients [5]. Secretin comes from the S cells in the duodenum and proximal jejunum, and it is released in response to the acidic environment generated by the gastric fluids in the duodenal lumen. It inhibits gastric secretions and emptying, increases the production of mucus and, along with CCK, it stimulates the pancreatic secretion of water and HCO3-. Motilin is another peptide released periodically by the Mo cells and during the fasting period which stimulates the gastric and small intestine motility enabling the movement of food into the large intestine (phase III of the migrating motor complex). These hormone levels vary according to the food consumed decreasing after the ingestion of fat and glucose thus slowing the upper GI tract. The gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are incretins synthesized and secreted by enteroendocrine cells of the small intestine that stimulate insulin secretion from beta-pancreatic cells in a glucose-dependent mechanism. This involvement in the regulation of insulin concentrations makes the inadequate function of these endocrine peptides and reduced circulating levels to be linked to the development of type 2 diabetes. Somatostatin, on the other hand, displays mainly neuroendocrine inhibitory effects in multiple systems and is produced in different locations, among them, in enteric neural cells and D cells in the duodenum. It is stimulated by the ingestion of proteins and fat, and it reduces the secretion of water and electrolytes, the absorption of amino acids, the gallbladder emptying and CCK production, and the release of insulin resulting in diabetes.

3. Indications for duodenal exclusion

Duodenal exclusion (DE) can be used as a complement to different procedures. Whereas foregut diversion is the shared element, the final objectives meant to achieve with the exclusion vary according to the operation conducted.

In metabolic surgery, procedures that combine the restriction of food intake and the exclusion of the proximal intestinal segment such as Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD) have shown to induce a greater weight loss and higher T2DM resolution rates compared to restrictive procedures without intestinal exclusion [11, 12]. Moreover, the fact that the anti-diabetic effects occur rapidly and are noticeable within days after surgery, implies that these benefits are independent of weight loss or caloric restriction and that exclusion of the foregut produces changes in glucoregulatory mechanisms and glucose homeostasis [3, 13]. The foregut hypothesis [3, 14] suggests that metabolic surgical procedures that exclude the duodenum and proximal jejunum prevent ingested food from activating a diabetogenic signal from these segments of the small intestine thus improving glucose metabolism. The physiologic response to food ingestion is mediated by incretins such as GIP and GLP-1 which promote insulin secretion. In addition to this incretin effect, nutrients in the gastrointestinal tract activate negative mechanisms mediated by anti-incretin factors to compensate for the glucose-lowering effects of incretins and other postprandial processes. The exertion of a negative effect on insulin makes anti-incretin signals promote insulin resistance and T2DM. Therefore, because of bypassing the upper intestinal tract, the release of these factors is avoided enhancing the action of incretins from the hindgut.

Another indication for DE is severe or complicated peptic ulcer disease (PUD). Despite decreases in its incidence and rates of hospital admission and mortality with the advent of effective pharmacological agents, there is still an estimated prevalence between 5–10% [15]. Alcohol consumption, smoking, long term NSAID use, and the incidence of the Helicobacter pylori infection are all contributing factors. Among the associated complications, bleeding is the most common one, followed by perforation, obstruction, and malignancy. Perforation, although less frequent, is the prevailing indication for emergency surgery causing approximately 40% of all ulcer-related deaths [15, 16]. When the size of the ulcer prevents an adequate primary closure alone, duodenal exclusion with or without resection can be employed. In the case of gastric PUD, distal gastrectomy can be performed if needed with concomitant vagotomy and reconstruction. Duodenal PUD can be managed by simple transection pre- or post- pyloric, thereby excluding the duodenum from alimentation, and reconstruction.

Complex traumatic duodenal injuries (grade III or greater according to the American Association of Surgery for Trauma Organ Injury scale) have also been traditionally treated with duodenal exclusion [17]. The management of these wounds is challenging since they are usually accompanied by associated injuries and have significant mortality and morbidity. Protection of the primary repair by diverting the duodenum may prevent dehiscence and fistula formation with an eventual improvement in patient’s outcomes. Initially, the exclusion procedure described by Berne [18] consisted in diverticulizing the duodenum; the duodenal injury was repaired and a vagotomy, antrectomy, gastrojejunostomy, tube duodenostomy, and T tube biliary drainage were done. This technique was effective in excluding the biliary and pancreatic secretions but too complex and time-consuming considering the usually fragile condition of the patient. Therefore, it was substituted with a simpler procedure, introduced by Jordan [19], that shares the same objective of decompression of the duodenum. While maintaining the primary repair of the duodenal injury, it closes the pylorus through a gastrotomy that is used later to place the gastrojejunostomy eliminating the need for gastric resection. A spontaneous opening of the pylorus is seen approximately 30 days after surgery.

In the case of gastric outlet obstruction, either due to benign or malignant conditions, a gastroenteric anastomosis with exclusion of the duodenum and proximal small intestine can be done as a first step in the treatment of the disease or as a palliative measure for inoperable cancers.

4. Metabolic surgery that includes duodenal exclusion

4.1 Roux-en-Y gastric bypass

Roux-en-Y Gastric Bypass (RYGB) has four main components: a small gastric pouch, a biliopancreatic limb, a gastrojejunostomy, and a jejunojejunostomy.

A small gastric pouch (approximately 50 mL) is constructed primarily by dividing the lesser curvature of the stomach and excluding a large portion of the fundus, entire greater curvature, and distal stomach, along with the duodenum, and first portion of the jejunum. The biliopancreatic limb consists of the remnant stomach proximally, the duodenum, and proximal jejunum and it drains the biliary and pancreatic digestive enzymes into the alimentary limb at the second, distal anastomosis. It is created by dividing the jejunum approximately 50 cm from the Treitz ligament. The Roux-en-Y technique is used to avoid a loop gastroenterostomy and the bile reflux that this may generate. A Roux limb of approximately 100 cm to 200 cm is measured past the jejunal resection, and at this point, the biliopancreatic limb is anastomosed with the alimentary limb via jejunojejunostomy. To perform the gastrojejunostomy, the Roux limb is brought up to the gastric pouch and an anastomosis created.

RYGB can be a demanding procedure with a longer learning curve, given the number of steps it requires and the need for 2 anastomoses. These steps increase the operation time compared with simpler techniques such as sleeve gastrectomy.

Weight loss is obtained due to restrictive and hypoabsorptive mechanisms [2, 11]. The creation of a gastric pouch restricts the quantity of food that can be ingested whereas the rearrangement of the anatomy by bypassing most of the stomach and the first part of the small intestine limits the absorption of calories and nutrients. The exclusion of these segments also favors a rapid improvement in hyperglycemia and finally T2DM resolution. The fact that these benefits begin to be noticed only days after the procedure without a significant weight loss, implies that the changes in the different glucose regulatory mechanisms, in the release of gastrointestinal tract hormones, and the intestinal microbiota are responsible for this endeavor. The latter mainly consists of anaerobic microorganisms that inhabit the intestinal tract and may have an important role in the pathogenesis of T2DM and obesity. Due to the anatomical modifications with RYGB, unaltered food will directly reach the distal small intestine for digestion and nutrient absorption thus relocating the microbiota which may favor weight loss and metabolic improvement.

The main complications associated with RYGB include bleeding, anastomotic ulcer, anastomotic leak or stricture, internal hernia, dumping syndrome, nutritional deficiencies, reactive hypoglycemia, diarrhea, and gallstones [20]. The overall risk of major technical complications is typically <1% when done by a high-volume surgeon at an established center. Given the known malabsorptive consequences, vitamin and mineral supplements should be prescribed after surgery, including multivitamins, calcium, vitamin B12, vitamin D, and iron. Moreover, blood tests should be performed on regular basis to gauge vitamin and mineral levels (Figure 1).

Figure 1.

Roux-en-Y gastric bypass.

4.2 One anastomosis gastric bypass (OAGB)

The OAGB was created to compensate for the technical complexity of the RYGB.

The procedure has two main components: a long and narrow gastric pouch and a 150–200 cm jejunal bypass (biliopancreatic limb) with a single anastomosis, the gastrojejunostomy. The stomach is divided parallel to the lesser curvature creating a narrow and longitudinal gastric pouch after passing a bougie for sizing, preserving the pylorus. The anastomosis between the jejunum and the gastric pouch is done 150–200 cm distal to Treitz’s ligament.

The percentage of weight loss and the improvement and resolution of associated comorbidities especially diabetes is similar in both, RYGB and OAGB. As with all the procedures involving duodenal exclusion, nutritional supplementation is needed although a higher risk for iron and fat-soluble vitamins deficiency has been observed with OAGB due to the length of the biliopancreatic limb which is believed to aggravate malabsorption. This has led to some surgeons reducing the length of the limb from the 200 cm size to 150 cm in patients, especially with a body mass index (BMI) < 50 kg/m2.

Despite sharing some complications with RYGB such as the risk of hemorrhage, anastomotic ulcer, anastomotic leak, dumping syndrome, and hypoglycemia, fewer side effects can be expected [21]. The fact that there is only one anastomosis, and the absence of mesenteric division may reduce the rate of anastomotic leak and internal hernias, respectively. Two specific complications associated with OAGB are anastomotic ulcers and bile reflux [22]. Anastomotic ulcers can be treated with medical therapy, treatment of H pylori if applicable, smoking cessation, etc.…. However, it may become chronic and a revisional surgery may be required to modify the OAGB to either a RYGB or even to restore the normal anatomy. Bile reflux through the gastrojejunal anastomosis can cause severe symptoms of abdominal pain, food intolerance, and reflux symptoms. It can increase the risk of dysplasia, and gastric and esophageal cancer. Endoscopic surveillance should be performed in symptomatic patients given the possibility of malignancy. In case of persistent bile reflux, revisional surgery with conversion to a RYGB, or restoration of original anatomy should be considered (Figure 2).

Figure 2.

One anastomosis gastric bypass.

4.3 Biliopancreatic diversion

Biliopancreatic diversion (BPD) includes three main components: the creation of a gastric pouch, a long Roux limb, and a short common channel. The stomach is divided, and gastric volume is reduced to 300–500 cc. Classic BPD as described by Scorpinaro in 1979 is done in a horizontal fashion with resection of the distal stomach and pylorus. The small intestine is divided at 250–300 cm from the ileocecal valve creating the alimentary limb which is anastomosed to the gastric pouch as a gastroileal anastomosis. The long biliopancreatic limb is attached to the alimentary limb, performing an end-to-side ileoileal anastomosis generating a 50–100 cm common channel.

BPD is an extremely effective operation in terms of weight loss and treatment of obesity-related comorbidities such as heart disease, high blood pressure, and especially T2DM with a high-resolution rate [23, 24]. Despite having a restrictive component given the stomach resection, it is considered mainly a hypoabsorptive procedure. The reduced absorption of fat and the hormonal effects that result from diverting the flow of food from the bile and pancreatic secretions causes a significant decrease in cholesterol levels, long-term weight loss, and metabolic changes through modifications in incretin levels. Although there are important benefits, there are two main complications associated with BPD: post gastrectomy syndrome and nutrient malabsorption [24, 25]. Due to the distal gastrectomy with resection of the pylorus, diarrhea, dumping, bile reflux and marginal ulcerations are not uncommon. Bypassing much of the small intestine predisposes to fat malabsorption and thus deficiencies of vitamins A, D, E, and K. Therefore, supplementation with water-soluble analogs of vitamins A, D, E, and K is recommended in addition to other vitamins and minerals, including B12, calcium, and iron since the long-term risk of protein malnutrition and bone demineralization is not rare. In case of severe malabsorption and malnutrition and unmanageable diarrhea, revisional surgery can be indicated consisting of elongation of the common limb and a reduction of the gastric pouch (Figure 3).

Figure 3.

Biliopancreatic diversion.

4.4 Biliopancreatic diversion with duodenal switch

The biliopancreatic diversion with duodenal switch (BPD-DS) includes three specific components: a longitudinal or sleeve gastrectomy preserving the pylorus, a 250 cm total alimentary limb, and a 100 cm common channel. A mildly restrictive sleeve gastrectomy (SG) starting 5–7 cm from the pylorus is created since the main objective is to decrease acid production and maintain normal gastric emptying in contrast with SG as a single procedure, in which the sleeve must be much more restrictive due to the absence of an associated small bowel bypass. The duodenal dissection and transection constitute the specific step in the duodenal switch. The duodenum is resected 3–4 cm distal to the pylorus and the small intestine is transected 250 cm from the ileocecal valve to create the alimentary limb. A duodenoileal anastomosis is created between the biliopancreatic and alimentary limb 100 cm away from the ileocecal valve to create the common channel. The mesentery defects are then closed.

This procedure and especially the duodenal transection can be technically challenging due to the proximity of important structures. Visualization of the common bile duct may be used as a landmark for the dissection and posterior resection of the duodenum.

BPD-DS is performed in often performed in patients with a BMI of 50 or more that were not able to lose weight with any other treatment. Like with BPD, the restrictive and hypoabsorptive components of the BPD-DS cause significant weight loss and metabolic improvement [24, 26]. These benefits are even more pronounced than with RYGB experiencing better outcomes regarding T2DM, hypertension, and hypercholesterolemia resolution. The sleeve gastrectomy, due to the reduction of D cells in the stomach, lowers ghrelin levels enhancing satiety. Moreover, rapid entry of food into the distal intestine given the bypass may increase peptide YY levels which improve satiety. BPD-DS, by including pylorus preservation, and creating an anastomosis post-pyloric, addresses the high incidence of post gastrectomy symptoms seen with the original BPD, mainly dumping, marginal ulceration, and bile reflux. The effectiveness in decreasing marginal ulceration is believed to be related to the gastric resection since a reduced number of parietal cells leads to less acid production. Also, the Brunner glands that remain in the first part of the duodenum secrete mucus which may protect the ileal mucosa.

The complexity of this procedure and the possibility of long-term consequences due to impaired nutrient absorption have limited its utilization. The complication rate after BPD-DS is usually higher compared with other bariatric surgeries not only because of the difficulty of the technique but also since it is done in superobese patients with more associated metabolic complications [24]. With that said, BPD-DS can be done as a second stage surgery after a patient has initially completed a sleeve gastrectomy. If done intentionally as the second of a two-stage procedure, this should decrease the morbidity associated with operating on a very high weight individual. Cholecystectomy may be done as an elective procedure as the chances of having gallstones increase due to the loss of bile salts from interruption of their enterohepatic recirculation. Furthermore, in the case of choledocholithiasis, the utilization of an endoscopic approach is more challenging given the difficulty to access the bile duct.

Like BPD, hypoabsorption of fat and the excretion of bile acids predispose to deficiency of fat-soluble vitamins as well as other vitamins, iron, and calcium. To avoid nutritional deficiencies and future complications such as osteoporosis, supplementation and monitoring are needed (Figure 4).

Figure 4.

Biliopancreatic diversion with duodenal switch.

4.5 Single anastomosis duodenal switch (SADI)

SADI is a simplification of the BPD- DS. The procedure has two main components: a sleeve gastrectomy preserving the pylorus and a single duodenoenterostomy. After the SG is created and the duodenum transected, a duodenoileal anastomosis between the proximal duodenum and a loop of the ileum) is done by replacing the Roux-en-Y reconstruction with a single-anastomosis. The length of the common channel is increased to 300 cm from the ileocecal valve.

These modifications were developed to reduce the main drawbacks of the BPD- DS which include technical considerations with constructing a Roux-en-Y configuration with 2 anastomosis and side effects from having an ultra-short length of the common channel. The rearrangement to the loop configuration may also benefit absorption since it changes the flow of the biliopancreatic secretions that before were diverted distally. While the length of the common channel must be no less than 300 cm, the size of the sleeve may vary. It does not have to be as restrictive as with an SG as a single procedure, avoiding side effects regarding limitations in food ingestion and rapid emptying into the small bowel.

SADI, compared with other classic hypoabsorptive metabolic surgeries is technically simpler with only one anastomosis, has a restrictive and hypoabsorptive component favoring weight loss and obesity-related comorbidities improvement, and the preservation of the pylorus avoids post gastrectomy symptoms. As with the other surgical procedures, possible complications are related to hemorrhage, anastomotic leakage, and strictures. Nutritional deficiencies are still a possible side effect and vitamins and minerals supplementation must be monitored and taken accordingly, but the creation of a 300 cm common channel has significantly improved the issue of malnutrition (Figure 5).

Figure 5.

Single anastomosis duodenal switch.

The field of bariatric surgery is constantly changing as new studies are being developed with the aim of having a better understanding of the molecular changes associated with these procedures. Hopefully, this will lead to the advent of new treatments with higher benefits and lower risks, allowing for better and tailored therapies. One of the fields of interest is the role of bile acids as a signaling molecule for different plasma membrane and nuclear receptors given their favorable metabolic effects related to weight loss and glucose tolerance after surgery. Adipose tissue circulating micro RNAs (miRNAs) are also being studied as there is evidence showing that alterations in their profile may change the gene expression and reduce the activation of inflammatory mediators thus improving insulin signaling [27]. In addition, due to the favorable impact that bariatric surgery has shown in improving or resolving diseases that are correlated with higher morbidity and mortality, the possibility of broadening the indications and including patients with lower BMI before the development of obesity-related metabolic complications should be considered.

5. Conclusion

Duodenal exclusion is used in surgery for multiple reasons. It can be used to treat primary pathology, such as peptic ulcer disease, malignancy, gastric outlet obstruction, or after trauma. It is also used in metabolic surgery to add a hypoabsorptive effect for weight loss and a beneficial impact on various co-morbidities. There are additional neurohormonal implications of duodenal exclusion that vary, depending on where the intestine is divided, and how long of a common channel or absorptive limb is left in place. The impact on diseases such as diabetes is mediated via complex pathways that continue to be researched today. Duodenal exclusion exhibits indisputable benefits but is linked to well-known side effects and complications. Understanding the physiological importance of the duodenum, the implications of its exclusion, the variety of methods for reconstruction and their impact is important in caring for these patients after surgery.

Conflict of interest

The authors declare no conflict of interest.