In the past, excess acid contact with the jejunum had been considered the primary mechanism for ulcer formation, although the mechanism for this excess acid has been debated. After surgery, basal production of acid in the gastric pouch decreases because gastric acid is mainly produced in the body and fundus of the stomach; however, the proximal pouch invariably also contains acid-producing parietal cells [23–25]. Many of the ulcers reported in the early experience with gastric bypass developed in patients who had large proximal gastric pouches greater than 50 mL [26]. The larger parietal cell mass in the pouch was thought to create a higher volume of gastric acid that did not reach the antrum and duodenum. Thus, there was a decrease in inhibitory feedback to antral G-cells, upregulated gastrin, and thereby increased gastric acid secretion [23]. Subsequent investigators believed that by reducing the pouch size, decreasing the acid secretion from the pouch, the ulcer rate would decrease [5, 9]. Sapala et al. reported a series of 1,120 patients with the micropouch gastric bypass [9]. This technique consists of constructing a micropouch limited to the gastric cardia and offers reliable weight control and improvement in comorbidities. However, in this series, the rate of ulcer and/or stenosis was 16%, a figure that parallels results with larger pouches. Other surgeons prefer to isolate the fundus from the pouch by limiting the pouch to the lesser curvature. Unfortunately, oxynic cell mass is concentrated along the proximal lesser curvature, which explains why marginal ulcer in these kinds of pouches appears to be more common than in greater-curvature pouches.

An increase in acid production in patients with marginal ulcers has been documented despite the presence of a small gastric pouch [21, 25, 27, 28]. These findings suggest that individual differences in parietal cell distribution may be one important risk factor for the development of marginal ulceration. Mason et al. found that 43% of their patients had a low pH within the pouch, and serum gastrin levels were universally low after gastric bypass [23]. Thus, it was postulated that in patients who continue to have low gastric pH after surgery, vagal innervations may dominate acid secretion.

Another risk factor could be the reflux of acid from the distal “bypassed” stomach into the proximal pouch in patients who have staple line disruptions. Staple line dehiscence is seen primarily when the pouch is created by an undivided staple line through the proximal stomach. Jordan et al. identified stomal ulcers in 34 out of 412 (8.2%) patients after gastric bypass, two-thirds of whom had staple line disruption [29]. Clearly, once a connection between the gastric remnant and the pouch is established, the jejunal mucosa is exposed to a greater volume of low-pH fluid. Most likely because the jejunal mucosa does not have intrinsic protection from an acidic environment, only small amounts of acid production can cause ulceration [2].

The potential role of gastric acid in the development of marginal ulcers is further supported by evidence that, in many patients, acid suppression alone is effective in healing marginal ulcers [7, 13, 15, 21, 30].

The prolonged irritation by foreign material (staples or suture material) (Fig. 10.2) has been proposed as a precipitating factor for marginal ulcer formation. Capella et al. saw a decrease in the marginal ulcer rate from 5.1 to 1.5% by switching from a stapled to a hand-sewn gastrojejunostomy and by using absorbable sutures for the inner layer and permanent sutures for the outer layer [12, 13]. The marginal ulceration rate further decreased to 0.4% when absorbable sutures were used for both layers [13]. Vasquez et al. studied whether the choice of reinforcing suture material for the 25 mm circular stapled anastomosis affected the incidence of marginal ulcers [16]. Marginal ulcers were noted in 10% of cases: 13.4% in whom permanent suture was used for reinforcement compared with 2.3% when absorbable suture was used (p  =  0.03). In a study of 3,285 patients, the marginal ulceration rate was significantly higher when the inner row of the gastrojejunostomy was constructed with permanent suture (2.6%) rather than absorbable suture (1.3%) [10]. In this study, the incidence of visible suture adjacent to the ulcer on endoscopy was also significantly reduced (64.3% vs. 3.4%; p  <  0.001). Contrarily, in the study of Rasmussen et al., suture remnants were visible in 32% of the ulcer beds (44% of the cases with permanent suture and 20% with absorbable suture) [14]. However, in these studies, it is difficult to quantify other factors that may also influence the incidence of ulcer development such as smoking, NSAID use, and other comorbidities. Furthermore, Sacks et al. did not find ­statistically significant differences between absorbable vs. nonabsorbable sutures in the development of marginal ulcers [10].