Omitting nasogastric tube placement after gastrectomy does not enhance postoperative recovery: a propensity score matched analysis

Enhanced recovery after surgery (ERAS) program has become the main trend in gastrointestinal surgery. This study aims to investigate factors influencing the decision-making of nasogastric tube (NGT) placement and its safety and efficacy after gastrectomy. We analyzed our prospectively maintained database including 287 patients who underwent elective gastrectomy in our department from January 1 to December 31, 2017. All cases were divided into two groups, namely, the no-NGT group and the NGT group. Logistic regression was used to analyze factors that affected the decision of NGT placement, and propensity score matching (PSM) was later applied to balance those factors for the analysis of safety outcomes between groups. Multivariate analysis showed resection range (p = 0.004, proximal gastrectomy: OR = 4.555, 95%CI = 1.392–14.905, p = 0.016; total gastrectomy: OR = 1.990, 95%CI = 1.205–3.287, p = 0.009) was the only independent risk factor of NGT placement. NGT was omitted in the majority (58.8%) of distal gastrectomy but only in 42.5% and 25% in total and proximal gastrectomy. After PSM, we found no significant differences between patients with or without NGT in postoperative hospital stay, time to first flatus and defecation, time to fluid and semi-fluid diet, rate of reinsertion, or hospitalization expenditure (p > 0.05, respectively). The incidence of postoperative complications in the two groups were 21.7% and 23.5%, respectively (p = 0.753), and the incidence of major complications was 7.0% and 9.6% (p = 0.472). The decision-making of NGT placement is mainly influenced by the resection range. Omitting NGT is a safe approach in all types of gastrectomy but was not able to enhance the recovery in our practice.


Introduction
Ever since Kehlet first proposed the concept of enhanced recovery after surgery (ERAS) in 1997, it has been carried out successfully in varied surgical fields. Nowadays, rapid recovery after operations has gradually become a clinical routine in gastrointestinal surgery. With the deep understanding of rapid recovery after gastrectomy, many studies question the necessity of a nasogastric tube (NGT) after gastrectomy [1][2][3]. The international guidelines [4] and domestic expert consensus [5] recommend that there is no need to insert NGT routinely in patients with gastrectomy, and several randomized controlled trials (RCT) [6][7][8][9][10] and meta-analyses [1,11] have provided strong evidence against the routine use of NGT after gastrectomy.
However, NGT is routinely used in the majority, if not all, of gastric cancer patients after gastrectomy in China. With the accumulating evidence against the routine use of NGT, it is yet unclear which factors exactly influence the decisionmaking of NGT placement in China. Moreover, whether omitting NGT is safe in the setting of Chinese clinical practice also requires more evidence for verification. Since 2017, our department has gradually educated the ERAS program in gastric cancer patients. Surgeons were also encouraged to Qi Wang and Zhouqiao Wu are contributed equally to this work. avoid tube placement when considering safety. In this study, we retrospectively analyzed our prospectively maintained database to explore the influencing factors of the decisionmaking of NGT placement, to evaluate whether omitting NGT accelerates the postoperative recovery of patients after gastrectomy, and last but not least, to assess whether it is safe after gastrectomy without NGT.

Patient and clinical data registration
In this study, we included patients who underwent elective surgery for the gastric tumor in ward I of the Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute from January 1, 2017, to December 31, 2017. Patients who met any of the following criteria were excluded from the analysis: previous history of gastric surgery (except endoscopic resection), emergency surgery (acute perforation, obstruction, bleeding, etc.), laparoscopic exploration, endoscopic resection. During that time, placing NGT was no longer restricted as a clinical routine, and the surgeons might choose not to place the tube when they thought it was safe to do so. We collected the patients' demographic data, clinical pathological characteristics, and perioperative information from a prospectively maintained database [12]. Moreover, since 2017, we prospectively registered the postoperative complication data following the APPEAL study protocol [13,14], and the severity of complications was scored using the Clavien-Dindo grading system [15] continuously by one set clinical researcher. The postoperative complication data were retrieved from this database to ensure the objectiveness and quality of the data.

Perioperative management
The perioperative management of patients was consistent with our ERAS protocol. In short, 1 day before the operation, laxative was applied to the patients with no additional mechanical bowel preparation. Patients were fasted from solid food for 12 h, while they were suggested to drink 250 ml 10% glucose on the morning of the operation. Prophylactic antibiotics were administrated for one dose before the operation and 1-2 doses afterward during the perioperative period (in total within 24 h). After surgery, patient-controlled analgesia was given to patients for the first three postoperative days, and additional non-steroidal anti-inflammatory drugs or opioids were administrated when acute pain occurred accordingly. In general, patients were recommended to drink water (in a small amount) on the first day after surgery, and Resection range the total amount of food intake gradually increased daily after surgery based on the patient's feelings and the doctor's judgment. Patients were allowed to take soft food if they have good tolerance of liquid or their bowel function was recovered. We also encouraged them to ambulate at an early stage, usually on the first day after surgery. The patients were discharged when they met the following criteria: satisfied mobility, tolerance of soft food intake for at least one day, not suspicious of complications [5].

Types of gastrectomy
The main procedures used in our department include distal gastrectomy (resection of the distal two-thirds of the stomach and anastomosis of the proximal stomach to the small bowel) or total gastrectomy with anastomosis of the esophagus to the small bowel [16]. During the inclusion period of this study, proximal gastrectomy is generally used for early gastric cancer located in the upper 1/3 of the stomach or gastroesophageal junction (EGJ) and remedial surgery after endoscopic treatment (EMR or ESD). Sufficient residual stomach volume should be satisfied after resection; that is, the residual stomach volume should reach at least 1/2 of the pre-resection volume. Local gastrectomy (LG) refers to non-circumferential resection of the stomach, which is mainly applicable to patients with early gastric cancer without lymph node metastasis and some patients with gastric stromal tumor. In general, laparoscopy and endoscopy are combined to perform full-thickness local resection of the gastric wall [17]. All surgeries in our study were performed by experienced chief surgeons at our center.

Study endpoints
The major purpose of our study is to determine whether omitting NGT accelerates postoperative recovery in our clinical setting. Therefore, we choose the primary endpoint as the length of postoperative hospital stay, which was defined as the day from the first day after surgery to the day of discharge (including the day of discharge). To achieve this, we first investigated what are the major factors that influence the decision-making of NGT placement by logistic regression, and then a propensity score matching (PSM) was performed to control the influence of the identified independent risk factor(s) between the groups. In the regression analysis, we included the patient characteristics and intraoperative data into the univariate and multivariate analyses, which were performed by non-conditional logistic regression analysis, and the factors with predictive value in univariate analysis were included in multivariate analysis. The nearest neighbor method was used in the PSM, and the caliper width was set to 0.1. The clinical features between the two groups were compared after PSM.
The other recovery outcomes included the time to first flatus and defecation, the time to fluid and semi-fluid diet, and the rate of tube reinsertion. The hospitalization expenses, as one major advantage of the ERAS program, were also measured. In addition to the recovery outcomes, we also measured the safety outcomes (i.e., postoperative complications) between the two corrected groups. The diagnosis and classification of complications were based on Clavien-Dindo classification, and we defined those grade III or higher complications as severe complications [15]. The complications included in this study and the diagnostic criteria were referred to the APPEAL study [13,14] and were first recorded by the doctors and double-checked by a set researcher. The study design is shown in Fig. 1.

Statistical analysis
In statistical analysis, the continuous variables such as age, blood loss, and postoperative hospital stay were described as the mean ± standard deviation if the Kolmogorov-Smirnov test was consistent with a normal distribution. Otherwise, the median was used. For the classified variables such as gender, TNM stage, and tumor location, we described the number of cases and percentage. Differences in variables among groups were tested using Student's t-test, chi-square test, or Fisher's exact test. However, non-parametric tests (the Kruskal-Wallis or Mann-Whitney test) were used for variables with skewed distributions. Bilateral p < 0.05 was considered statistically significant. We used SPSS version 24.0 (IBM SPSS Software) for all statistical analyses.

Patient characteristics
The study collected a total of 303 patients with gastric tumor who received surgery from January 1, 2017, to December 31, 2017. There were 16 cases excluded for various reasons (see Fig. 1), resulting in a total of 287 patients included for analysis. These cases were divided into two groups, namely, the no-NGT group (n = 147) and the NGT group (n = 140). The patients' demographic data, clinical pathological characteristics, and perioperative information are summarized in Tables 1, 2, and 3.

Influence factors of nasogastric tube placement
Univariate analysis (Table 4 showed factors with p < 0.2; complete data including all factors were shown in supplementary data, Table S1) showed that resection range (p = 0.004) and lymph node dissection range (p = 0.032) were significantly correlated with NGT placement. These two (p < 0.05), together with the preoperative pathological differentiation, clinical TNM stage, operative approach, multiple organ resection, and surgeon (0.05 < p < 0.2, respectively), were included in the multivariate analysis (Table 5), and we found that only the resection range (p = 0.004) was the independent influence factor of NGT placement. NGT was omitted in the majority (58.8%) of distal gastrectomy but only in 42.5% and 25% in total and proximal gastrectomy.

Postoperative recovery and safety
To further determine the impact of NGT on postoperative recovery, we used PSM to balance the differences between the two groups in the resection range. After being screened and matched, a total of 230 patients were included, and 115 patients were assigned to the NGT' group and the no-NGT' group, respectively. The patients' characteristics (resection range) before and after PSM were shown in Table 6 (complete data including all factors after PSM were shown in supplementary data, Table S2). In the analysis of the primary endpoint, no statistical differences were found between the two groups (9 days in the no-NGT' group versus 10 days in NGT' group, p = 0.344, Table 7). Non-parametric tests also showed no statistical differences in the other recovery parameters including the time to first flatus and defecation and the time to fluid and semifluid diet (p > 0.05, respectively). The rate of reinsertion and hospitalization expenses between the no-NGT' group and the NGT' group were not significant either (p > 0.05, respectively). The median duration of the NGT was 2 days (1-15 days) in NGT' group.
The overall complication rate was 24.4% and the severe complication rate was 8.0% in the 287 patients before PSM. And those were 22.6% and 8.3%, respectively, after PSM, with no statistical differences between the groups in overall complication rate (21.7% versus 23.5%, p = 0.753) or severe complications (7.0% versus 9.6%, p = 0.472, Table 7). Comparisons of each respective complication are listed in Table 7.

Subgroup analysis
As our multivariate analysis showed that the resection range was the only independent factor that influenced the tube placement, we conducted the subgroup analysis in patients with distal gastrectomy and those with proximal or total gastrectomy, aiming for any factor influencing the tube placement in those two subgroups. In the proximal or total gastrectomy group, we did not find any further independent factor determining the tube placement (see supplementary data, Table S3.1 and S3.2), while in the distal group, the pathological differentiation (well to moderately differentiated and well-differentiated, OR = 14.345, 95%CI = 1.517-135.671, p = 0.020) and operative approach (totally laparoscopic, OR = 0.395, 95% CI = 0.187-0.832, p = 0.014) were the independent factors that influence the tube placement (see supplementary data, Table S4.1 and S4.2). We also compared the postoperative recovery and safety parameters of the two subgroups and found no significant differences between patients with or without NGT in neither subgroup (see supplementary data, Table S5, S6, and S7).

Discussion
Despite the accumulating data suggesting to omit NGT for gastric cancer surgery, many Chinese centers still routinely apply it when the ERAS guidelines [4] recommend the opposite. Our retrospective analysis of the prospectively maintained database revealed that in our practice, the resection range is the main course of NGT placement. We also found there was no significant difference in postoperative recovery in patients with or without NGT in our clinical setting. Our data might help surgeons to have new insights into the practice strategy of the ERAS program after gastrectomy.
One major finding of our research is that surgeons' choice of placing NGT is mainly influenced by the resection range, i.e., proximal and total gastrectomy. NGT is more often placed when the surgeon estimates a high risk of the surgical approach which might eventually result in anastomotic or other complications after surgery [18]. Importantly, it turned out that those two resection ranges were indeed had higher complication rates when compared to distal gastrectomy (data not shown). In the latter group, NGT was omitted in the majority (58.8%), with satisfactory recovery and safety outcomes. From this point of view, our data demonstrate that the surgeons' decision-making of NGT placement is, at least, reasonable.
However, our data also suggest such an effort of NGT placement in high-risk patients did not result in better safety outcomes. In this prospective registry, the complication rates (overall 28%) were comparable to the other studies [19]. For proximal or total gastrectomy, doctors choose to insert NGT partly because the decompression effect may prevent leakage into the thoracic cavity, but  In addition, as shown in Table 7, there was no statistical difference in the reinsertion rate of NGT between the two groups, and all 21 patients (9.1%) who underwent reinsertion were due to postoperative complications. We summarized the reasons and found that most of them were postoperative gastrointestinal complications, including anastomotic leakage (7 cases), other abdominal infection except the leakage (2 cases), gastrointestinal hemorrhage (5 cases), gastrointestinal obstruction (3 cases), delayed gastric emptying (3 cases), and intra-abdominal hemorrhage (1 case). It seems that reinsertion of the NGT remains one important intervention strategy for gastrointestinal complications in clinical practice.
As one critical element in the ERAS programs, many studies report bowel function recovery as the main outcome to investigate whether NGT placement delays its recovery. One commonly used parameter is the time to first flatus. Varied results were reported regarding whether NGT shortens the time to first flatus [20]. Our data, in accordance with the meta-analyses [3,21] and the prospective randomized controlled trial [10], showed no effect in this regard. However, it is important to notice that the time to flatus is not a good indicator of bowel function recovery [22], let alone its occurrence is quite subjective in clinical practice. In contrast, the study by van Bree et al. [23] indicates that tolerance of solid food and first defecation is a better indicator of bowel function recovery instead. Due to a difference in postoperative diet between Chinese and Western cultures, time to semi-liquid instead of solid food is used to indicate the bowel function in our study. But no difference was found in either time to semi-liquid or time to first defecation in our study. Similar results were also reported by Hu et al. [24], although many other studies reported earlier defecation in the no-NGT group [25,26].
On top of bowel function recovery, the ultimate purpose of the ERAS program is to yield a safe and faster recovery after surgery; hence, we chose the postoperative stay, instead of the bowel recovery outcomes, as our primary endpoint in this study. Unfortunately, the good safety outcomes in the no-NGT did not result in shorter hospital stay (e.g., postoperative stay, prolonged hospitalization) in our analysis. This is probably because omitting NGT is only one small procedure in the concept of ERAS and itself may not have enough influence on the whole picture, especially when an ERAS protocol had been running routinely in our practice. Of course, our study is also subject to its retrospective nature and limited to a relatively small group size. These limitations may also influence the statistical power of our results.

Conclusion
In this retrospective analysis of our prospectively maintained database, we found that the decision-making of NGT placement was mainly influenced by the resection range in gastric cancer surgery. Omitting NGT is a safe approach in all types of gastrectomy but was not able to enhance the recovery in our practice.
Authors' contributions Study conception and design: WZQ and LZY conceived of the study. Acquisition of data: WQ, SJY, and HSY collected patients' data. Analysis and interpretation of data: WQ and ZY provided statistical analysis and interpretation. Drafting of the manuscript and critical revision of the manuscript: WQ and WZQ were the major contributors in drafting and revising the manuscript. JJF, LZY, SF, and LSX provided the necessary administrative support for the study. All authors contributed to the refinement of the study protocol and approved the final manuscript.
Funding This study is funded by the Beijing Municipal Science & Technology Project, Beijing Municipal Science & Technology Commission (D131100005313010), and National Key Technology Research and Development Program of the Ministry of Science and Technology of China (2014BAI09B02). Neither of them was involved in the study design, data collection, analysis and interpretation of the data, or manuscript writing.

Data availability
The datasets generated and/or analyzed during the current study are not publicly available because they are derived from the patient database of the center and hence subject to confidentiality but are available from the corresponding author on reasonable request.
Code availability Not applicable.

Declarations
Ethics approval and consent to participate The current study is approved by the Peking University Cancer Hospital Ethics Committee (2016YJZ32). This study is a retrospective analysis of our prospectively maintained database. It does not require the permission/consent of the participants.

Conflict of interest
The authors declare no competing interests.