Impact of Laparoscopic Sleeve Gastrectomy on Gastrointestinal Motility

Objective Laparoscopic sleeve gastrectomy (LSG) was considered mainly as a restrictive procedure due to anatomic alterations in the upper gastrointestinal tract. Additionally, due to neurohormonal alterations, LSG modifies the gastrointestinal motility, which controls appetite and feeling of satiety. Aim The aim of the study was to review the impact of laparoscopic sleeve gastrectomy on gastrointestinal motility. Material and Methods A search of the medical literature was undertaken in Pubmed, Web of Science, and Cochrane library. Esophageal, gastric, bowel motility were assessed separately. Results Nine studies assessed esophageal motility. The data remain debatable attributing to the heterogeneity of follow-up timing, surgical technique, bougie size, and distance from pylorus. The stomach motility was assessed in eighteen studies. Functionally, the sleeve was divided into a passive sleeve and an accelerated antrum. All scintigraphic studies revealed accelerated gastric emptying after LSG except of one. Patients demonstrated a rapid gastroduodenal transit time. The resection of the gastric pacemaker had as a consequence aberrant distal ectopic pacemaking or bioelectrical quiescence after LSG. The bowel motility was the least studied. Small bowel transit time was reduced; opposite to that the initiation of cecal filling and the ileocecal valve transit was delayed. Conclusion Laparoscopic sleeve gastrectomy has impacts on gastrointestinal motility. The data remain debatable for esophageal motility. Stomach and small bowel motility were accelerated, while the initiation of cecal filling and the ileocecal valve transit was delayed. Further pathophysiological studies are needed to evaluate the correlation of motility data with clinical symptoms.


Introduction
Laparoscopic sleeve gastrectomy (LSG) is the most frequently performed procedure in the world and has overtaken the "gold standard" Roux-en-Y gastric bypass (RYGB), which remains the most performed bariatric/metabolic procedure only in Latin/South America. The trend analysis demonstrated that LSG had the largest average annual percentage increase of approximately 9% from 2013 of the worldwide bariatric/metabolic surgical procedures [1]. Laparoscopic sleeve gastrectomy is positioned between the adjustable gastric banding and RYGB in terms of morbidity with effectiveness comparable to RYGB even at five years [2,3].
Laparoscopic sleeve gastrectomy involves the removal of the gastric fundus and greater curvature portion of the stomach, leaving only a lesser curvature tube. Yehoshua et al. showed that after the sleeve, the fundus, which is the most distensible part of the stomach, is removed, thus leaving a sleeve which is characterized by markedly lesser distensibility and high intraluminal pressure, leading to the feeling of early satiety [4]. The abstraction of the fundus is related to physiological alterations in the upper gastrointestinal tract, since the angle of His and the receptive relaxation mechanism is abolished, and the gastric pacemaker is abandoned. Furthermore, the antrum is preserved in some cases depending on the distance of the resection, and the pylorus remains intact. These physiological changes are expected to provoke motility alterations at the gastrointestinal tract.
The aim of the study was to review the impact of laparoscopic sleeve gastrectomy on gastrointestinal motility.

Search Strategy.
A search of the medical literature was undertaken in Pubmed, Web of Science, and Cochrane library until August 2017. The keywords used were "sleeve gastrectomy" AND (motility OR gastrointestinal motility OR esophageal motility OR gastric motility OR bowel motility OR emptying OR manometry).

Eligibility Criteria
2.2.1. Types of Studies. All studies assessing the impact of LSG on gastrointestinal motility were included. Esophageal, stomach, and bowel motilities were assessed separately.

Types of Participants.
The types of participants were obese patients (BMI > 30) undergoing laparoscopic sleeve gastrectomy.

Types of Outcome
Measures. The outcomes measured were esophageal, gastric, and bowel motility.

Inclusion and Exclusion
Criteria. Two independent reviewers (Eleni Sioka and Konstantinos Perivoliotis) screened abstracts, reviewed full text versions of all studies classified, and extracted data. Any trial considered relevant was retrieved for further review. The full texts were independently assessed by two reviewers. Disagreements were resolved with a third reviewer. Only published articles in the English language were included. Meta-analysis, systematic reviews, letters to the editor, case studies, non-English language publications, duplicate studies, experimental studies, and conference papers were excluded.
2.4. Data Extraction and Quality Assessment. One reviewer (Konstantinos Perivoliotis) extracted data from selected trials and a second reviewer (Eleni Sioka) checked for accuracy. The data were standardized and extracted from each study, and data were recorded into a database. The variables collected were first author, year of publication, country, type of study, number of participants, method of assessment, timing points, and main findings.

Study Selection.
One hundred seventy eight studies were screened for eligibility and fifty two studies assessed in full text. Twenty four studies were excluded due to various reasons. Finally, 28 studies were eligible to be included in the review ( Figure 1). There was complete agreement among the authors as to the inclusion of these studies.
The postoperative follow-up ranged from 6 days to 50 months. The bougie size ranged from 32 to 40F. The distance from the pylorus ranged from 2 to 6 cm. The lower esophageal sphincter (LES) length was reduced in three studies [5,9,13] increased in two studies [6,10], and unchanged in one study [8]. The LES resting pressure decreased in four studies [5,10,11,13], increased in two studies [6,12], and remained unchanged in two studies [8,9]. The amplitude pressure was reduced in two studies [5,11], increased in one study [10], and unchanged in one study [8]. Amplitude pressure decreased in distal esophagus and increased in the other parts in one study [6]. Ineffective motility was reported in four studies. The percentage was increased from 10% to 45% postoperatively in one study [9], while it was the same preoperatively (7%) in another study [10], was increased at 5% (1/20 patients) in one study [11], and was reported at 37.7% (20/53 patients) in another study [7]. The  percentage of normal peristaltic contractions was not affected in one study [11], while it increased in another study [5]. The summary of studies is reported in Table 1 [25], two studies in India [26,27], one study in New Zealand [28], one in Egypt [29], one in Chile [30], and one in Israel [31]. Twelve studies were prospective studies, four studies were prospective randomized controlled studies [14,17,22,27], and two were retrospective studies [18,25]. The method of gastric emptying assessment was gastric scintigraphic studies in fourteen studies and magnetic resonance imaging (MRI) in one study [23], while one study assessed the gastric slow-wave pacemaking using laparoscopic high-resolution (HR) electrical mapping [28], and two studies assessed the gastroduodenal transit time by radiological upper gastrointestinal series [18,25]. The postoperative follow-up ranged from 3 to 24 months. The bougie size ranged from 32 to 48F. The distance from the pylorus ranged from 2 to 8 cm. All studies showed accelerated gastric emptying after LSG except for one [31]. Functionally, the sleeve was divided into a passive sleeve and an accelerated antrum. The patients demonstrated a rapid gastroduodenal transit time. The resection of the gastric pacemaker had as a consequence aberrant distal ectopic pacemaking or bioelectrical quiescence after LSG. No correlation was observed between gastric emptying and postprandial symptoms in one study. No correlation was found between gastroduodenal transit time and weight loss in one study [25], while in another study, patients showing a rapid gastroduodenal transit had better weight loss than patients presenting with a slow voiding rate [18]. The summary of the studies are presented in Table 2.

Bowel Motility.
Three studies assessed the bowel motility. Two were prospective studies and one was prospective randomized study. One study was conducted in Japan, one in Greece, and one in India [21,27,32]. Trung et al. evaluated the intestinal motility using cine MRI preoperatively and 3 months postoperatively and found reduced intestinal transit time leading to accelerated intestinal motility [32]. Melissas et al. evaluated prospectively 21 patients preoperatively with a g-camera and 4 months postoperatively. Apart from the acceleration of small bowel transit time, the authors showed that initiation of cecal filling and the ileocecal valve transit was delayed [21]. Similarly, Shah et al. showed decreased small bowel transit time after LSG [27] (Table 3).

Discussion
The aim of this study was to review the impact of laparoscopic sleeve gastrectomy on gastrointestinal motility. The gastrointestinal motility research might be essential to recognize the behavior of the created sleeve, to explain possible clinical symptoms-implications, and to elucidate possible mechanisms of actions of this procedure. According to the Second International Consensus Summit for Sleeve Gastrectomy, the panel of experts voted the following as mechanisms of action: restriction: 79%, gastric emptying: 0%, hormonal: 16%, malabsorption: 0%, and other: 3% [33]. Since 2007, LSG was characterized as more than a restrictive procedure [19]. Additional supportive evidence came from studies assessing hormonal alterations after LSG. Concerning hormonal changes, it seems that patients experienced a pronounced and long-lasting decrease of circulating ghrelin and increased postprandial release of the CCK, GLP-1, and PYY, the so-called gut peptides after LSG. It was hypothesized that the faster delivery of nutrients to the distal intestinal tract postoperatively may provoke increased the postprandial release of the gut peptides contributing to the improvement of glucose control as well as to the reduction of food intake and subsequently body weight [34].
The esophageal motility was assessed in several studies. The limitations of the studies include the small sample size. The data remain debatable. The variability in the outcomes of esophageal motility may be attributable to the timing of postoperative follow-up, the variability of surgical techniques, the different bougie sizes, and the different dissections from pylorus, thus creating a sleeve with variable distensibility and intraluminal pressure with, in part, the preservation of the antrum. The percentage of peristaltic normal contractions increased postoperatively and is not statistically significant at 3 months [11] but statistically significant later [5]. It seems that the motility of the body of the esophagus was normalized. Perhaps, this might be attributable to the reduced intrabdominal pressure due to weight loss. An increase in the esophageal acidification was reported in few studies [9,11]. Del Genio et al. pointed out a decrease in the esophageal transit after LSG in impedance study. Furthermore, the authors explained the reflux episodes as a consequence of retrograde movements into the esophagus [9].
Gastric motility emerges as the role of the stomach as an endocrine organ. Gastric motility acts as a central mediator of hunger, satiation, and satiety. Gastric emptying plays a key role in regulating food intake. Gastric distention acts a satiety signal to inhibit food intake [35]. During food intake, it is the gastric distention and gastric accommodation that regulate satiation in a manner. After food intake, when the stomach empties gradually, it is the gastric emptying and the intestinal exposure of the nutrients that play a key role, while the role of gastric distention follows. It seems that gastric accommodation and gastric emptying are implicated in the regulation of gastric distention and intestinal exposure of nutrients, thus control satiation and satiety. The correlations between gastric accommodation, gastric emptying, and body weight suggest that gastric motility may also affect the long-term regulation of body weight [36].
A number of studies assessed gastric motility. Baumann et al. showed that the sleeve was completely motionless without any coordinate peristalsis, while the antrum had faster peristaltic folds, concluding that gastric emptying is directly linked to the function of the antrum when the antrum is preserved in LSG [23]. It seems that the resection NR/NR The increased intragastric pressure occurred very frequently in patients after SG (77%) and was not associated with any upper GI symptoms, specific esophageal manometric profile, or impedance reflux. Impedance reflux episodes were also frequently observed after SG (52%): they were significantly associated with gastroesophageal reflux (GER) symptoms and ineffective esophageal motility. The sleeve volume and diameters were also significantly smaller in patients with impedance reflux episodes (p < 0 01).  The LSG significantly increased the lower esophageal pressure independent of weight loss after LSG and may protect obese patients from gastroesophageal reflux.

Seven of them
presented LESP of <12 mmHg and ten patients presented LESP of <6 mmHg after the operation. Furthermore, the abdominal length and total length of the high pressure zone at the esophagogastric junction were affected.
A sleeve gastrectomy produces an important decrease in LES pressure, which can, in turn, cause the appearance of reflux symptoms and esophagitis after the operation due to a partial resection of the sling fibers during the gastrectomy. When dividing groups into type 2 diabetic patients and nondiabetic patients, the speed in nondiabetic patients is significantly higher for the 3 cm group.
The residual volume increases significantly in both groups, and there are no differences between them. Gastric emptying is faster in patients with antrum resection.
The distance does not influence the gastric emptying of diabetic patients.  It remains to be determined whether the weight loss will continue beyond that period. In the antrum resection group, an increase in gastric emptying postoperatively was noted.
Complications such as failure of stomach evacuation were not observed in the RA group; even more radical resection of the pyloric antrum performed by LSG is possible without concerns of postoperative disorder of the stomach evacuation function  [23], Germany Prospective pilot study 5 MRI 1 day before LSG and 6 days and 6 months after LSG 32F/5-6 cm The dynamic analysis showed that antral propulsive peristalsis was preserved immediately after surgery and during follow-up, but fold speed increased significantly from 2.7 mm/s before LSG to 4.4 mm/s after 6 months. The sleeve itself remained without recognizable peristalsis in three patients and showed only uncoordinated or passive motion in two patients. Consequently, the fluid transport through the sleeve was markedly delayed, whereas the antrum showed accelerated propulsion with the emptying half-time decreasing from 16.5 min preoperatively to 7.9 min 6 months after surgery.
The stomach is functionally divided into a sleeve without propulsive peristalsis and an accelerated antrum. Accelerated emptying seems to be caused by faster peristaltic folds. 13    When the whole group of 14 patients was studied, there were also no significant changes in T-lag, T1/2 and %GE between 6 and 24 months postoperatively.
Constant effect of SG in the acceleration of gastric emptying of solids, which occurs faster, not only in short but also in long-term postoperatively 18 Melissas, J. et al., 2007 [19], Greece Prospective study 23 The scintigraphic measurement of the gastric emptying of a solid meal preoperatively and 6 months postoperatively.
Gastric emptying studies using radioisotopic technique before and 6 months after the operation. 34F/7 cm Although the meal size was drastically reduced, the meal frequency increased postoperatively in 12 patients (52.2%).  There was a consensus except for one study that gastric emptying was accelerated. The rapid gastric emptying was also strengthened by the observation of our team that a significant proportion of patients experienced dumping syndrome upon provocation at six weeks and 6 and 12 months after LSG. These symptoms included both early and late symptoms suggesting that LSG may lead to changes in eating patterns after LSG, especially in sweeters [37,38]. Only one study showed no effect on gastric emptying. In this study, the follow-up was done in 3 months, and the created sleeve was performed using a bougie 48F at a distance of 6 cm from the pylorus [31]. Therefore, the sleeve might be large enough without increasing its intraluminal pressure.
There is still a debate concerning the maintenance of the antrum in order to avoid interference with the gastric physiology or its resection to increase the restrictive mechanism. Abdallah et al., who compared groups with resections at 2 cm versus 6 cm distances from the pylorus, showed that there was statistically significant excess weight loss between the groups, concluding that increasing the size of the resected antrum was associated with better weight loss, without increasing significantly the rate of complications [39]. Similarly, Obeidat et al. showed that patients with resection at 2 cm distance from the pylorus experienced statistically significant better maintained weight loss than did patients with resection at 6 cm [40]. On the contrary, ElGeidie et al. found no statistical differences regarding weight loss at the groups at 2 cm and 6 cm from the pylorus [41]. Vives et al. showed that gastric emptying was faster in the group with the resection at 3 cm from the pylorus compared to that at 8 cm from the pylorus at 6 and 12 months postoperatively [14]. Unlike the previous, Fallahat et al. compared the gastric emptying in patients at 4 cm and 7 cm distance from pylorus 3 months postoperatively. The authors showed that resection at 4 cm from the pylorus were associated with delayed gastric emptying, and resection at 7 cm from the pylorus, with accelerated gastric emptying. The authors speculated that resection at 4 cm from the pylorus had as a consequence neural innervations of the antrum being abolished, contributing to slower emptying. These patients experienced nausea, vomiting, and poor appetite. On the other hand, the resection at 7 cm from the pylorus preserved the contractility of the antrum, leading to rapid gastric emptying due to the absence of redistribution process since the body and fundus were excised. These patients complained of dumping-like symptoms and had more frequent meals [42]. Further prospective randomized trials are needed to compare the motility changes and clinical symptoms in patients with the preservation or not of antrum.
There is scant information concerning the possible explanation of how these motility alterations may affect clinical symptoms or explain the underlying mechanisms of action. It seems that the technique is not standardized, and different sleeves are created. Thus, different residual gastric volumes are produced. Since now, no clear association was found between gastric volume and weight loss. Researchers suggest that the physiological changes and not the size of the sleeve are responsible as mechanisms of action. What is known is that LSG changes the profile of gut hormones. Sista et al. showed that the rapid gastric emptying was correlated with the increased production of GLP-1 in the distal bowel [16]. Burgerhart et al. associated postprandial symptoms with gastric emptying. No difference on gastric-emptying characteristics was found between patients with low or high postprandial symptoms [24]. Pomerri et al. found that patients presenting with a rapid gastroduodenal transit experienced better weight loss than patients presenting with a slow voiding rate [18]. It seems that little is known regarding the underlining mechanisms by which LSG controls appetite and food intake. Since the data are restricted to medium term, it would be interesting to see if the sleeve behaves differently in the long term and how weight regain is explained in some patients.
Bowel motility was the least studied. It seems that the food reaches the terminal ileum faster but arrives at the cecum later. Thus, the contact of the food with the area of terminal ileum is extended. Perhaps, this altered interaction of food with the gastrointestinal tract may be a key component to explain the neurohormonal changes via the stimulation of intestinal L cells producing incretions and understanding the underlining mechanisms which improve the metabolic profile of the patients.
The limitations of the review include the lack of standardization of the surgical technique, the different follow-up timings, the different measured outcomes, the small sample siz,e and the lack of available long-term data beyond four years.
Further pathophysiological studies are needed to investigate the exact correlation of the motility parameters with the clinical symptoms and gut peptide alterations and potential hormonal interactions between gastrointestinal tract and brain.

Conclusion
Laparoscopic sleeve gastrectomy has impacts on the gastrointestinal motility. The data remain debatable for esophageal motility. The stomach and small bowel motilities were accelerated, while the initiation of cecal filling and the ileocecal valve transit was delayed. Further pathophysiological studies are needed to investigate the exact correlation of the motility parameters with the clinical symptoms and gut peptide alterations.