3.1 Operation time
Six studies which reported the operation time were included in this meta-analysis. Using a Random model (I2 = 54%), the results of meta-analysis indicate that operating time was significantly shorter in Billroth II group (OR = 34.14; 95%CI, 24.19-44.08; P < .00001). The result of RCTs and OCS subgroup both reveals that the operating time was significantly shorter in Billroth II group. [RCTs (I2 = 81%, OR = 34.71; 95%CI, 13.81-55.61; P < .00001), OCS (I2 = 0%, OR = 31.16; 95% CI, 21.08-41.24; P < .00001)] (Fig. 2).
3.2 Intraoperative blood loss
Five included studies reported the intraoperative blood loss. Using a fixed model (I2 = 36%), Billroth II reconstruction was associated with a significant reduction in the intraoperative blood loss (OR = 54.32; 95%CI, 50.29-58.36; P < .00001) (Fig. 3).
3.3 Anastomotic leakage
Four studies which reported the incidence of anastomotic leakage included in this meta-analysis, using a fixed model (I2 = 0%). No significant difference between 2 groups in the incidence of anastomotic leakage (OR = 1.56; 95%CI, 0.66-3.64; P = .59). The meta-analysis of RCTs and OCS subgroup both reveals no statically different between two groups in incidence of anastomotic leakage. [RCTs (I2 = 0%, OR = 3.07; 95% CI, 0.61-15.41; P = .67), OCS (I2 = 0%, OR = 1.13; 95% CI, 0.4-3.16; P = 1.13)] (Fig. 4).
3.4 Postoperative mortality
Five studies which reported the postoperative mortality in this meta-analysis. Using a fixed model (I2 = 0%), no significant difference between two groups in the incidence of postoperative mortality (OR = 1.15; 95%CI, 0.38-3.51; P = .80) (Fig. 5).
3.5 Overall postoperative morbidity
Seven studies which reported the incidence of overall postoperative morbidity in this meta-analysis. Using a fixed model (I2 = 0%), no significant difference between 2 groups in the incidence of overall postoperative morbidity (OR = 0.92; 95%CI, 0.6-1.42; P = .72). The meta-analysis of RCTs and OCS subgroup both reveals no statically different between 2 groups in overall postoperative morbidity. [RCTs (I2 = 0%, OR = 1.22; 95% CI, 0.67-2.23; P = .51), OCS (I2 = 0%, OR = 0.69; 95% CI, 0.37-1.27; P = .23)] (Fig. 6).
3.6 Delayed gastric emptying
Three included studies reported the incidence of delayed gastric emptying. Using a fixed model (I2 = 0%), no significant difference between two groups in the incidence of delayed gastric emptying after operation (OR = 0.84; 95%CI, 0.40-1.77; P = .65). (Fig. 7).
3.7 Dumping symptoms
Five included studies reported the dumping symptoms (palpitation, suffusion, perspiration and vertigo) after surgery. Using a fixed model (I2 = 0%), the results of meta-analysis show that Roux-en-Y reconstruction was associated with a significant reduction in the incidence of dumping symptoms after distal gastrectomy (OR = 0.31; 95% CI, 0.13-0.73; P = .008). (Fig. 8).
3.8 Reflux symptoms
Five included studies reported the reflux symptoms. Using a fixed model (I2 = 0%), the result of meta-analysis revealed that Roux-en-Y reconstruction was associated with a significant reduction in the incidence of reflux symptoms after distal gastrectomy (OR = 0.20; 95% CI, 0.10-0.42; P < .0001). The result of RCTs and OCS subgroup both reveals Roux-en-Y reconstruction had significantly lower incidence of reflux symptoms. [RCTs (I2 = 0%, OR = 0.13; 95%CI, 0.04-0.46; P = .001), OCS (I2 = 0%, OR = 0.27; 95% CI, 0.11-0.70; P = .007)] (Fig. 9).
3.9 Remnant gastritis
Seven included studies reported the incidence of remnant gastritis. Using a fixed model (I2 = 8%), the results of meta-analysis show that Roux-en-Y reconstruction was associated with a significant reduction in the incidence of remnant gastritis (OR = 0.12; 95% CI, 0.08-0.17; P < .00001). The result of RCTs and OCS subgroup both reveals that Roux-en-Y reconstruction had significantly lower incidence of remnant gastritis. [RCTs (I2 = 38%, OR = 0.14; 95%CI, 0.09-0.22; P < .00001), OCS (I2 = 0%, OR = 0.07; 95% CI, 0.03-0.17; P < .0001)] (Fig. 10).
3.10 Reflux esophagitis
Six included studies reported the incidence of reflux esophagitis. Using a fixed model (I2 = 0%), the results of meta-analysis show that Roux-en-Y reconstruction was associated with a significant reduction in the incidence of reflux esophagitis (OR = 0.26; 95%CI, 0.15-0.44; P < .00001). The result of RCTs and OCS subgroup both reveals Roux-en-Y reconstruction had significantly lower incidence of reflux esophagitis. [RCTs (I2 = 0%, OR = 0.28; 95%CI, 0.13-0.63; P = .002), OCS (I2 = 0%, OR = 0.24; 95% CI, 0.12-0.49; P < .0001)] (Fig. 11).
4 Sensitivity analysis
Sensitivity analysis was conducted by excluding studies that were of relatively low quality (Feng et al and Shao et al). The study data did not change with respect to the outcomes of overall postoperative morbidity, dumping symptoms, remnant gastritis, and reflux esophagitis following exclusion (Table 6). The results suggest that the excluded studies had low publication bias on the outcomes. Besides, our results were robust to the sensitivity analysis for Feng et al and Shao et al, and the results reported in this study are acceptable.
4.1 Publication bias
The deviation of shape in a funnel plot can indicate publication bias. There was no obvious asymmetry in the funnel plot (Fig. 12), which indicated a low publication bias.
Billroth-I gastroduodenostomy is usually performed in Japan and Korea. This kind of anastomosis can be carried out with minimal tension. Billroth-I is also more physiological because it maintains the normal passage of food into the duodenum. Billroth II and Roux-en-Y reconstructions are the 2 most commonly used techniques when Billroth I reconstruction is not applicable after distal gastrectomy. As far as we know, Billroth II reconstruction is often used because of its simplicity. However, the disadvantage of Billroth II anastomosis is remnant gastritis and reflux esophagitis; moreover, the reflux of intestinal contents into the esophagus and remnant stomach is also observed, which is closely related to the high risk of Barrett's esophageal or esophageal cancer and remnant gastric cancer after gastrectomy. The Roux-en-Y technique, on the contrary, significantly reduces the risk of bile reflux. However, it is more complicated to perform with more anastomoses. It also increases the difficulty to assess the bile duct during endoscopic retrograde cholangiopancreatography (ERCP). In addition, some patients may develop delayed gastric emptying known as Roux stasis syndrome with functional obstruction of the Roux limb. Zong et al. retrieved 15 studies involving Billroth I vs. Billroth II vs. Roux-en-Y following distal gastrectomy in 2011. This meta-analysis was an updated one and included more RCT and OCS studies to compare the clinical advantages between Billroth II and Roux-en-Y procedures regarding complications in the perioperative period and long-term outcome.
4.3 Perioperative outcome
The duration of surgery and the amount of intraoperative blood loss are important indicators to evaluate the safety of the intraoperative period. The results of this meta-analysis showed that the intraoperative blood loss was significantly lower and the operating time was significantly shorter in the Billroth II group, which can be explained by the additional anastomosis in Roux-en-Y reconstruction. Regarding the incidence of anastomotic leakage, no significant difference in the rate of anastomotic leak between the 2 reconstruction methods. This may be largely attributed to the refinement of technique and use of gastrointestinal stapling devices. Further, the results of this meta-analysis support that Roux-en-Y reconstruction does not carry greater postoperative mortality and overall postoperative morbidity than the Billroth-II reconstruction.
Some studies have shown that the Roux-en-Y anastomosis is associated with high incidence of delayed gastric emptying (Roux stasis syndrome) after Roux-en-Y, which is characterized by abdominal pain, vomiting, and nausea after oral intake of food. Some studies showed that the Roux stasis syndrome has been known to be prevalent in over 30% of patients after Roux-en-Y. Gustavsson et al suggested that Roux-Y stasis seems to be main caused by a functional obstruction of the Roux-Y limb rather than by a mechanical obstruction, he emphasized the importance of the length of the Roux-Y limb and the limb length longer than 40 cm was a higher risk of Roux stasis syndrome after surgery. What is more, some experts stated that the Roux-Y limb itself contributes to the development of the Roux stasis syndrome. This is perhaps because the Roux-en-Y anastomosis is known to damage the intestinal continuity and integrity of the intestinal nerve. The intestinal loops in Roux lack electrical activity from the duodenum after cutting off the jejunum. Morrison et al found that the direction of propagation of the jejunal pacesetter through Roux-Y limbs can sometimes be retrograde. This finding means Roux-Y limb have a retrograde moving sequence, which could result in stasis in the limb. Mathias et al determined that contractions of the Roux-Y limb were abnormal or even absent after surgery, and did not propel contents distally. Besides, Gustavsson et al found a lower incidence of Roux-Y stasis in patients with total gastrectomy, he speculated that the gastric acid produced by remnant stomach could pass into the Roux-Y limb and affect its motility. Although these factors result in delayed gastric emptying, the exact incidence and reason of Roux stasis syndrome is also debatable. The results of this meta-analysis showed that Roux-en-Y and Billroth-II anastomosis had no significant difference.
4.4 Medium and long-term outcome after operation
This meta-analysis showed that Roux-en-Y anastomosis was superior to the Billroth-II anastomosis in reducing reflux esophagitis and remnant gastritis. Billroth II is associated with deficiencies in reflux control, and duodenal juice reflux into the stomach can increase the value of gastric pH and destroy the normal gastric acid environment. The Roux-en-Y anastomosis was superior to the Billroth-II anastomosis in reducing bile and pancreatic juice reflux mainly because of the active function of the interposed jejunal “Y” limb, which can prevent the esophagus and stomach from being damaged by alkaline intestinal secretions. Prassana et al found that the structure of Roux-en-Y loop could decrease the incidence of duodenal reflux from 26% to 2%.
The refluxed bile and pancreatic juice not only cause reflux symptoms, but also is harmful to the mucosa of the gastric remnant. Lawson et al demonstrated that extensive gastritis was seen in remnant stomach after Billroth II, whereas after Roux-en-Y, no significant changes in gastric mucosa were seen. Vanheenden et al described that all patients after Billroth II gastrectomy had chronic atrophic gastritis, in addition to the appearance of intestinal metaplasia as early as 2 years after surgery. Moreover, the bile and pancreatic juice reflux into the stomach are the causative factors of remnant gastric carcinoma. Tersnette et al  demonstrated a significant increased incidence of gastric remnant carcinoma 15 to 20 years after Billroth II (OR = 1.48) in a meta-analysis. Ochiai et al reported that a mutant form of p53 protein was detected in 10% of patients who had duodenal juice reflux after distal gastrectomy. Werscher et al reported that duodenal juice reflux into the stomach caused adenocarcinoma in rats. Therefore, preventing duodenal juice reflux not only improves the quality of postoperative life but also reduces the risk of remnant gastric carcinoma. We can conclude that Roux-en-Y reconstruction following resection of the distal stomach is likely superior to Billroth II reconstruction in preventing remnant gastritis and reflux esophagitis, as it reduces gastroesophageal and duodenogastric reflux. However, gastroesophageal and duodenogastric reflux in some patients with Roux-en-Y reconstruction was likely attributed to pressure from the afferent loop to the remnant gastric cavity being lower than that to the efferent loop.
The results of this meta-analysis regarding dumping syndrome show that Roux-en-Y reconstruction reduces the incidence of dumping symptoms in comparison with Billroth-II reconstruction after surgery. However, the clear mechanisms of Roux-en-Y reconstruction in preventing dumping syndrome are not well known. It is supposed that the interruption of the migration motor complex and diminished jejunal contractions may play an important role in slowing down the transit of chyme through the Roux limb.[34,35]
The main limitations of this meta-analysis include reporting bias and clinical heterogeneity in the study. In this meta-analysis, almost all included OSCs had not performed an unbiased evaluation of endpoints, likely resulting in potential and degree of reporting bias. To reduce reporting bias, we tried to retrieve and include all reports that met the inclusion criteria and contacted the authors of the study to retrieve unpublished data. Although we were able to get unpublished results from authors and perform subgroup analyses according to study type (RCT/OSC), we cannot exclude all publication bias.
The clinical heterogeneity between studies cannot be ignored, which is related to the patient's characteristics, treatment methods, and monitoring. Operative experience and treatment of complications in different hospitals may produce different outcomes and increase heterogeneity between the included studies. Besides, narcotic drugs, especially opioids, may reduce gastrointestinal function. In addition, acid base and electrolyte imbalance may also affect gastrointestinal function. Although we try to control some covariates, we cannot adjust our analysis of all confounding factors.
To accurately compare the perioperative safety and long-term complications of Billroth-II and Roux-en-Y reconstruction after surgery, we suggest that researchers planning observational studies should carefully select appropriate databases, apply correct statistical methods, stringently collect information about potential interferences, and report on the details of the subjects. Besides, future studies should have clear and agreed definitions of complications and details regarding the therapeutic methods. Further well-designed, large multicenter RCTs are needed to investigate the long-term outcome and complications between these two reconstruction methods.
Roux-en-Y reconstruction does not carry greater postoperative complications than the Billroth II reconstruction. Furthermore, Roux-en-Y reconstruction can improve the postoperative quality of life owing to less remnant gastritis, reflux esophagitis, dumping symptoms, and reflux symptoms. Considering the long-term postoperative outcomes, Roux-en-Y reconstruction should be a better choice following resection of distal stomach.
Writing – original draft: Lirong He.
Writing – review, and editing: Yajie Zhao.
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Keywords:Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.
billroth-II; distal gastrectomy; meta-analysis; roux-en-Y