Authors: Chikashi Shibata, Kentaro Sawada, Atsushi Mitamura, Toru Nakano
Categories: Review, distal gastrectomy, gastric emptying, liquid emptying, scintigraphy, solid emptying
Source: Journal of Smooth Muscle Research
Doi: 10.1540/jsmr.61.20
accelerated or delayed?
Authors: Chikashi Shibata, Kentaro Sawada, Atsushi Mitamura, Toru Nakano
Distal gastrectomy is the most frequently performed procedure for gastric cancer. Gastric emptying after distal gastrectomy is generally considered to be accelerated due to resection of the antrum, pylorus, and duodenal bulb. Food residue, however, is frequently observed in the gastric remnant in patients after distal gastrectomy at the time of endoscopy after routine overnight fasting. This observation suggests delayed gastric emptying and conflicts with the general understanding of accelerated gastric emptying after distal gastrectomy. We searched for reports that evaluated the separate gastric emptying of liquids and solids with scintigraphy after distal gastrectomy in humans and also addressed the physiologic changes in gastric emptying after distal gastrectomy. Most all reports showed that gastric emptying of liquids after distal gastrectomy was accelerated compared to healthy controls, especially immediately after feeding. In contrast, some gastric emptying of solids was accelerated early after the meal ingestion, but thereafter emptying of solids remaining in the stomach was delayed beginning about 60 min after the meal in patients after distal gastrectomy. This delayed solid gastric emptying after distal gastrectomy was considered associated with food residue in the remnant stomach. We conclude that gastric emptying after distal gastrectomy was accelerated for liquids and solids soon after the meal ingestion but delayed for solids later than 60 min after the meal ingestion.
Distal gastrectomy (DG) is the most frequently performed procedure for gastric cancer. Abnormalities of gastric emptying (GE) after DG are considered to be closely associated with patients’ postoperative symptoms, and understanding the ‘physiologic’ changes in GE after DG is quite important in treating patients after DG who have symptoms associated with GE disorders. In normal individuals, GE is regulated by a motor event in response to several stimuli, including the content of protein, fat, and carbohydrates in the meal, the total calories, and the consistency (solid or liquid) of the meal (1, 2). After DG, however, GE is considered altered to some degree compared to normal individuals with an intact stomach, because of the resection of 2/3–3/4 distal stomach, pylorus, and duodenal bulb. Many individuals believe that GE after DG is accelerated especially because of the resection of the pylorus which functions as a resistance to GE (3); however, it is a well-known observation that food residue in the remnant stomach after DG is often observed at endoscopy after routine overnight fasting (4, 5), suggesting a delay in GE after DG which seems to conflict with general understanding that GE after DG is accelerated.
The aim of the present review was to describe the physiologic changes in GE of liquids and solids after DG and to answer the question, “is GE after DG generally delayed or accelerated?”.
Scintigraphy is a representative method and considered gold standard to measure GE (2). In scintigraphy, food labeled with radioisotope is ingested, and GE can be measured by counting radioactivity in the stomach. Scintigraphy has an advantage to measure GE of liquids and solids separately at the same time. Acetaminophen absorption and ^13^C breath tests can also measure GE (6, 7). In these two tests, substances absorbable in the small intestine but not in the stomach are administered orally, and concentrations of the substances are measured over time in the blood or inhalation; GE can be measured by analyzing time-concentrations curves. It is difficult to measure GE of liquids and solids separately in these two tests. We searched for published peer-reviewed reports measuring GE of liquids and solids separately with scintigraphy in humans. We excluded reports using methods including acetaminophen absorption and ^13^C breath tests due to reasons above. We also excluded reports which dealt with patients after antrectomy, partial gastrectomy, or segmental gastrectomy. Our study was limited to reports of 2/3–3/4 distal gastrectomies which would include most patients undergoing gastrectomy for mid to distal-based gastric cancer; however, we also included such gastrectomies in patients undergoing DG for peptic ulcer or other indications exclusive of gastroparesis.
A typical time-percentile retention in the stomach for liquids decreases exponentially
after isotope ingestion without a lag phase, while for solids, emptying decreases linearly
after a 10–15 min lag phase (1, 8, 9) as shown in Fig. 1Fig. 1. Typical time-retention curves in healthy controls. A typical time-percentile
retention in the stomach decreases linearly after a 10–15 min lag phase for solids
(solid line), while it decreases exponentially without a lag phase for liquids (dashed
line) after isotope ingestion. Tlag and T1/2 indicate the
duration of lag phase and the time necessary for half emptying of total ingested
radioisotope, respectively.. We analyzed percentile retention in the stomach at 15, 30, 60 and 120 min, the
Tlag, and the T1/2. Tlag indicates the duration of lag
phase and is usually unrecognizable for emptying of liquids. T1/2 means the time
necessary for half emptying of total ingested radioisotope.
The percentile retention in the stomach for liquids decreases exponentially after isotope ingestion without any lag phase. Several previous reports measured liquid GE in healthy controls and documented percentile retention in the stomach as 58–85% at 15 min, 22–77% at 30 min, 8–60% at 60 min, and 5–15% at 120 min (10,11,12,13,14,15). The percentile retention of solids in the stomach in normal controls decreases linearly after an early lag time. The retention rate in the stomach was 82–100% at 15 min, 72–96% at 30 min, 38–77% at 60 min, and 14–48% at 120 min in controls (10,11,12,13,14,15,16,17,18,19,20,21,22,23). These variations in retention times in healthy controls are probably explained by the type and consistency of the marker.
GE is regulated by coordinated motor events, including the tone of the proximal gastric remnant (gastric body), phasic peristaltic contractions in the antrum, and relaxation of the pylorus and duodenum (24). Gastroduodenal motor activity differs between the postprandial and the interdigestive states (25). Postprandial gastropyloroduodenal contractions are divided into three phases; ‘early’, ‘intermediate’, and ‘late’ (1). The early phase starts immediately after feeding and continued for 20–30 min, and the intermediate phase was observed for 90–120 min after the early phase. The late phase followed the intermediate phase and lasted for 6–8 h. This pattern of three phases of the postprandial motor pattern is associated with GE. Liquids are emptied as controlled by the pressure gradient between the gastric body and the duodenum (pressure pump) that exists primarily during the ‘early’ and ‘intermediate’ phases (24, 26). The early phase is characterized by receptive relaxation in the gastric body, a vagally mediated motor response to accommodate food without increasing intraluminal pressure (27). Solids are emptied actively during the intermediate and late phases by contractions in the gastric antrum synchronizing with pyloric relaxations and distally oriented duodenal contractions; this phenomenon is referred to as antropyloroduodenal coordination or the peristaltic pump (1, 24, 28). Postprandial motor pattern changes into the interdigestive pattern after the late phase. In the interdigestive state, migrating motor complexes (MMCs) are observed in the stomach and duodenum. Activity front of the MMCs has been referred to as phase III activity, and giant contractions in the gastric antrum during phase III coordinate with the widest opening of the pylorus (29). Large particles usually greater than 1 cm, which remain in the stomach beyond the late phase for 6–8 h, are expelled into the duodenum during phase III of the MMCs in the gastric antrum in association with the pyloric opening.
Nutrients in the upper small intestine have inhibitory effects on gastric antral motility and emptying (30, 31). CCK secreted from duodenal-upper jejunal mucosa inhibits gastric emptying (32). Thus, gastrointestinal hormones including CCK are considered putative mediators for this braking effect on GE. Neural pathways as well as humoral factors may be involved in the braking effect, as we reported an important role of extrinsic nerves in intraduodenal capsaicin-induced inhibition on gastric antral motility (33).
Liquid There were three reports (13,14,15) that
measured liquid GE after DG, and two of which reported accelerated GE of liquids; Kamiji et
al. (13) described GE in patients undergoing DG for
gastric cancer and peptic ulcer. They found that the emptying rate of a nutrient liquid meal
in the first 5 min was as high as 70%, while it was only 22–23% in normal controls. The
T1/2 was less than 5 min in 12 of 14 patients after DG, whereas it was 43 ±
16 min (mean ± SD) in controls. Hinder et al. (14)
studied GE of liquids using 6% dextrose as a test meal in patients after DG for peptic
ulcer. They found accelerated GE, because almost 70% of the ingested dextrose was emptied in
the first 10 min in patients after DG. In contrast, Rieu et al. (15) evaluated GE after DG for peptic ulcer disease, and found that
emptying of 5% glucose did not differ in terms of T1/2 between controls, DG with
Billroth-II (B-II) reconstruction or DG with Roux-en-Y (RY) reconstruction of gastroenteric
continuity. The average percentile retention in the stomach after DG, derived from these
studies, was 20–38% at 15 min, 18–35% at 30 min, 16–28% at 60 min, and 10–20% at 120 min.
These variations in retention times in patients after DG are probably explained by the type
and consistency of the liquid marker and whether a vagotomy was performed, as well as the
details of the techniques of measurement of retention.
Figure 2AFig. 2. Time retention curves for liquids (A) and solids (B) in healthy controls and after distal gastrectomy (DG). Liquid and solid emptying after DG was accelerated immediately after the meal ingestion compared with control. Subsequent emptying was delayed beginning about 15 min after the meal for liquids and after about 60 min for solids in comparison with control. shows range of percentile retention at each time for liquid GE derived from studies mentioned above in controls and in patients after DG. Exponential curves which fit within these ranges are drawn as dashed and solid lines for control and after DG, respectively (Fig. 2A). These time-retention curves indicate that liquid GE after DG was accelerated immediately after the isotope ingestion. GE for liquids after DG, however, was delayed thereafter, because the emptying rate later than after 15 min was approximately 60% for control and 20% after DG, respectively.
Solid There were four reports (14,15,16,17) that measured solid GE after DG compared to normal
controls, and all of them found accelerated GE of solids soon after the isotope ingestion.
Smout et al. (16) found that the Tlag
after DG was shorter than in normal controls (8 vs. 18 min); however, they also found that
the emptied amount after the initial lag phase did not differ between the two groups. Hinder
et al. (14) reported 25–35% of ingested solids was
emptied into the small intestine in the first 30 min after DG, while almost 100% remained in
the stomach in controls. However, retention rate in the stomach thereafter in patients with
DG tended to be higher than controls especially later than the 60 min time point. Rieu et
al. (15) reported that the Tlag was as
short as 4 and 5 min in patients after DG with gastroenteric reconstruction using RY and
B-II anastomoses, respectively, which were shorter than that the 10 min time lag in
controls. The same investigator, however, found that the T1/2 did not differ
between the three groups (68 and 54 min in patients after DG with RY and B-II
reconstructions, respectively, and 83 min in controls). Miedema et al. (17) described that the retention rate in the stomach
after DG and in controls at 60 min was 27% and 83%, while the T1/2 was 27 and
116 min, respectively, suggesting early acceleration of solid emptying. They also reported a
later slowing of the empty rate after DG, because the emptying rate between 60–120 min was
18% after DG and 33% in controls. Based on these studies, percentile retention in the
stomach after DG ranged from 73–80% at 15 min, 62–74% at 30 min, 28–58% at 60 min, and 8–52%
at 120 min. These variations in retention times in patients after DG are probably explained
by the type and consistency of the solid marker and whether a vagotomy was performed, as
well as the details of the techniques of measurement of retention.
Figure 2B shows a range of percentile retention derived from studies mentioned above at each time point for solid GE in controls and after DG. Typical time-percentile retention lines were drawn by connecting median values at each time point and are shown as a dashed line for control and a solid line after DG (Fig. 2B). The time lag after meal ingestion was shorter in patients with DG in comparison with controls. GE of solids early after DG was accelerated, because the slope of the line was steeper than that in controls; however, GE of solids did not differ between two groups between 15 and 60 min, because the slope of the two lines indicated that the emptying rate was comparable. GE after DG was considered delayed in comparison with controls later than 60 min, because the slope of the controls was steeper than that after DG.
The accelerated GE early after meal ingestion observed for liquids and solids was considered to occur independent of any phasic gastrointestinal motor event. Figure 3Fig. 3. The effects of procedures performed in distal gastrectomy (DG) on gastric emptying (GE) early after meal ingestion. shows the effects of procedures performed in DG on GE soon after feeding. The reduced gastric volume due to resection of the distal stomach leads to a reduction of storage function. In addition, a concomitant vagotomy obligated by the lymph node dissection of the lesser curvature for gastric cancer leads to a reduction of storage function due to loss of receptive relaxation. A reduction of storage function causes a rapid and exaggerated increase in intraluminal pressure in the residual stomach after DG, leading to rapid GE early after meal ingestion. The pylorus is resected and gastroenteric anastomosis is performed as a reconstruction in DG. Gastroenteric anastomosis results in the enlargement of gastric outlet, which leads to acceleration of GE due to loss of resistance to GE. In addition, as a result of gastroenteric anastomosis, enlarged gastric outlet is positioned at the lowest point in an upright or sitting posture. This anatomical change must also contribute to acceleration of GE associated with fall of foods due to gravity. Plasma concentrations of CCK peak at 20–30 min after feeding (34, 35). CCK, as mentioned in the above section, delays GE by inhibiting gastric antral motor activity. The absence of this braking effects of CCK due to antral resection in DG is also likely to contribute to accelerated GE soon after feeding. Although the precise mechanism of early dumping syndrome still remains obscure, extreme acceleration of GE soon after meal ingestion is considered to have a role in the syndrome (36). Various alternative procedures for DG, such as pylorus-preserving gastretomy or reconstruction of a neogastric pouch from the jejunum, have been proposed to prevent early acceleration of GE, the functional long-term results of which are yet to be fully determined (37, 38).
As shown in Fig. 2B, the retention rate of solids in the stomach at 120 min was about 30% for both controls and patients after DG. Because the time-retention line in controls later than 60 min was steeper than that after DG, the retention rate later than 120 min after a meal in the DG group was considered greater than that in controls. The presence or absence of food residue after an overnight fast in the stomach during endoscopic examinations in 374 patients who had undergone a DG was compared to that for 2,168 patients without history of gastrectomy (controls); the presence of food residue in patients after DG was statistically higher than that in control (18.7% vs. 0.3%, P<0.001) (39). The results of our review suggest that food residue in the stomach after DG often observed at endoscopy must be associated with delayed solid GE late after meal ingestion.
Delayed GE of solids after DG later than 60 min after a meal appears to be related to the lack of motor function, antropyloroduodenal coordination, associated with loss of the gastric antrum, pylorus, and duodenal bulb. Indigestible particles which remain in the stomach later than 6–8 h after feeding are emptied into the duodenum by phase III of MMCs in the interdigestive state thereafter. MMCs are observed in the vagally innervated residual stomach even after DG but not in vagotomized stomach (25). Because DG for gastric cancer necessitates vagal denervation due to lymph node dissection, MMCs are not likely to occur in the remnant stomach after DG for cancer. After DG, the absence of fasting-phase MMCs, which functions as the ‘interdigestive housekeeper’, is believed to impair the clearance of food residues from the remnant stomach.
GE after DG may be different between patients with gastric cancer and benign diseases such as peptic ulcer; vagotomy of the gastric remnant due to lymph adenectomy that accompanies DG for gastric cancer, is not performed in DG for some benign diseases which do not require vagotomy. Vagotomy is likely to alter GE function after DG, when considering the important role of the vagus nerve in regulation of proximal gastric tone and postprandial gastropyloroduodenal motor function (1). Other possible operative factors which could affect GE after DG are the extent of gastric resection (size of the gastric remnant), type of gastroenteric reconstruction, and possibly the size of the anastomosis although this has been highly debated. One limitation of this review is that we could not measure these other factors into consideration in interpreting results of previous studies. It is likely that time period after DG affects gastric motor function and GE; GE might differ between one month and one year after DG. Another limitation of this study might be that we did not take time period after DG into consideration.
In conclusion, GE of liquids and solids should be considered separately after DG. Results of this review suggest that accelerated emptying of liquids and solids occurs soon after the meal ingestion but is then delayed after 15 min for liquids and after 60 min for solids. This delayed emptying of solids appears to explain the observation of retained food residue in the remnant stomach frequently observed at endoscopy after overnight fasting.
The authors declare that they have no conflict of interest in association with the present study.