Double-tract reconstruction is superior in controlling reflux esophagitis and enhancing quality of life after proximal gastrectomy: Results from a prospective randomized controlled clinical trial in China

doi:10.21203/rs.3.rs-1960657/v2

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Research Article

Double-tract reconstruction is superior in controlling reflux esophagitis and enhancing quality of life after proximal gastrectomy: Results from a prospective randomized controlled clinical trial in China

https://doi.org/10.21203/rs.3.rs-1960657/v2

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Background

Proximal gastrectomy (PG) is an alternative function preserving surgery. The aim of this study was to prospectively compare double-tract reconstruction (DTR) and esophagogastrostomy (EG) after PG regarding the incidence of reflux esophagitis, quality of life (QOL)，nutritional status and surgical safety.

Method

This study was a prospective, randomized controlled trial conducted in a single institute. Patients eligible for PG were enrolled and randomly assigned to the EG group and DTR group. The characteristic of patients, parameters of surgical safety, the incidence of reflux esophagitis which was the primary outcome of this trial, nutrition status and the QOL were compared between the EG and the DTR group. Blinding was not involved in this trial.

Results

73 patients eligible for PG were enrolled in the study and randomly assigned to the EG group (37 patients) and DTR group (36 patients). The incidence of reflux esophagitis after PG was significantly lower in the DTR group than that of the EG group (8.3% vs. 32.4%, P=0.019). In multivariate analysis, reconstruction method was the only significant factor affecting the incidence of reflux esophagitis. The DTR group demonstrated a more favorable QOL than the EG group after PG in the global health status, emotional functioning and symptoms such as fatigue, nausea and vomiting, pain, insomnia, appetite loss, dysphagia, reflux, eating restrictions, anxiety, dry mouth and taste change were more severe in the EG group patients. Nutritional status was balanced within the EG group and the DTR group after PG including BMI, levels of hemoglobin, serum albumin and serum total protein. The operation time was longer in the DTR group than in the EG group (191min vs. 221min, P=0.001) while surgical safety was similar in the two groups regarding blood loss volume, postoperative complications and hospital stays.

Conclusion

Our research demonstrated that DTR was superior to EG after PG in terms of the incidence of reflux esophagitis and provided a more satisfied QOL without increasing surgical complications or sacrificing nutritional status, thus making DTR a better reconstruction method after PG.

Trial registration:

ClinicalTrials.gov, NCT03613142, registered on August 2, 2018.

proximal gastrectomy

double-tract reconstruction

reflux esophagitis

quality of life

Gastric cancer (GC) is estimated to be the fifth most commonly diagnosed malignant tumor and ranks fourth in mortality worldwide(1). China has the most gastric cancer patients worldwide and contributed 45% of new cases (478,000) in 2020(2, 3). Although the rate of GC has decreased in the past three decades, the number of new cases and deaths from GC are estimated to increase(4). Moreover, the incidence of proximal gastric cancer, including gastroesophageal junction (EGJ) cancer, has been rising over the past few decades(5, 6).

The traditional surgical approach for gastric cancer located in the upper third of the stomach, including the EGJ, is total gastrectomy(7, 8). However, total gastrectomy may cause nutritional disadvantages, especially with respect to vitamin B12 and iron, due to the lack of intrinsic factor secreted by parietal cells in the distal stomach, which results in megaloblastic anemia. Moreover, the loss of storage capacity of the stomach and the function of the pylorus may lead to prolonged food intake restriction(9, 10). Proximal gastrectomy (PG) is considered a gastric-preserving surgery and a curative method for early gastric cancer that is located in the upper one-third of the stomach; such treatment with PG is recommended by the Japanese guideline for gastric cancer(7, 11). A large retrospective study demonstrated that for EGJ adenocarcinoma less than 4 cm, complete lymphadenectomy of the distal portion of the stomach offers marginal survival benefits so that PG can be considered in these patients(12). Moreover, for advanced proximal GC patients with cT2-3 staging, since the incidence of No. 4d, 5, 6 and 12a lymph node metastasis is extremely low, proximal gastrectomy would also be a choice for these patients(13, 14). Since the distal part of the stomach and pylorus is preserved, PG not only causes an improved nutritional status that includes the hemoglobin level, serum total protein level, and serum albumin level but also yields a better quality of life (QOL) in terms of more food intake and less body weight loss(10, 15, 16).

The common reconstruction method for PG includes esophagogastrostomy (EG), double-tract reconstruction (DTR), and jejunal interposition (JI), with the former two procedures being more commonly adopted. Reflex symptoms (occurring as the result of preservation of the stomach and lack of the cardia) such as sour regurgitation, heartburn, chest pain, and anorexia, are associated with reflux esophagitis, which is most considered when choosing a construction method after PG(17, 18). Since the majority of PG patients are early gastric cancer patients or patients with relatively small tumors, the QOL after surgery is another crucial consideration along with the prognosis(19, 20). In another previous retrospective study, DTR demonstrated better prevention of reflux esophagitis and improved quality of life(21). However, there is no prospective trial comparing EG and DTR after PG. Therefore, the main purpose of this study was to compare the difference between DTR and EG after radical proximal gastrectomy, regarding the incidence of postoperative reflux esophagitis, the postoperative QOL, surgical safety, and the postoperative nutritional status.

Study design

This trial is a prospective, randomized controlled study conducted in a single large cancer center, Peking University Cancer Hospital Gastrointestinal Cancer Center. Patients eligible for radical proximal gastrectomy from January 2019 to May 2021 were enrolled and randomly assigned to the DTR group or the EG group. The study conformed to the Declaration of Helsinki and was approved by the Ethics Committee of Peking University Cancer Hospital (No. 2018KT97). This trial was registered on the ClinicalTrials website on 02/08/2018, before patient recruitment (NCT03613142) and the trial protocol was available on the ClinicalTrials website.

Patients

Patients aged 18 to 80 years, with an Eastern Cooperative Oncology Group performance status score of 0 or 1, histologically confirmed adenocarcinoma, without metastasis, located in the upper one-third stomach and classified at clinical stage T1N0M0 (8th edition of the Union for International Cancer Control/American Joint Committee on Cancer TNM staging) or those with gastroesophageal junction cancer (Siewert type II or III) with a diameter less than 4 cm, who were eligible for R0 radical PG were involved in the study. Patients with distant metastatic lesions, with synchronous gastric cancer or malignancies in other organs, with a previous gastric surgery history (not including endoscopic resection) or with other conditions not suitable for surgery were excluded from the study. All patients volunteered to participate and signed informed consent forms with Dr. Xin Ji before enrollment. The enrollment took place at the Peking University Cancer Hospital, from January 2019 to May 2021. A computer‐generated list of random numbers was used to assign patients following simple randomization procedures into the DTR group or the EG group.

Surgery

All patients first underwent laparoscopic exploration to exclude peritoneal metastasis. Then, patients without metastasis underwent radical proximal gastrectomy with standard lymphadenectomy according to the Japanese gastric cancer treatment guidelines, which required resection of the upper half of the stomach and the abdominal segment of the esophagus with lymph node dissection of No. 1, 2, 3a, 4sa, 4sb, 7, 8a, 9, and 11p(7). Finally, EG or DTR was performed. Determination of whether a patient would be into the DTR group or the EG group was made by reference to a statistical series based on random sampling numbers by Dr. Xin Ji. DTR procedure (shown in supplementary files.): After transection of the esophagus, the 25 mm anvil of the circular stapler was inserted directly into the esophagus stump or by the transoral anvil delivery system (EEA OrVil™). The jejunum was transected 20 to 25 cm below the Treitz ligament. The distal jejunum was anastomosed with the esophagus by end-to-side anastomosis, and the jejunal stump was closed with a 60 mm linear stapler. The gastrojejunostomy was performed 15 cm below the esophagojejunostomy with side-to-side anastomosis by a 60 mm linear stapler, and the jejunojejunostomy was performed 15 cm below the gastrojejunostomy with side-to-side anastomosis by a 60 mm linear stapler. The common entry holes of the gastrojejunostomy and the jejunojejunostomy were closed by a linear stapler or manual suture. EG procedure: The placement of the anvil was the same as mentioned before; then, the esophagus was directly anastomosed with the remnant stomach by a 25 mm circular stapler with the anastomosis located in the anterior wall of the greater curvature of the gastric remnant.

Follow-up

Gastroscopy was performed approximately twelve months after the operation to evaluate reflux esophagitis according to the Los Angeles Classification of Gastroesophageal Reflux Disease. A nutritional evaluation was performed every three months after the operation, including the measurement of body weight and examination of the level of hemoglobin, albumin, and total protein in the blood test. QOL was assessed by the EORTC QLQ-C30 (version 3.0) and STO22 questionnaires approximately twelve months after surgery.

Endpoint

The primary endpoint of the study was the incidence of reflux esophagitis after surgery, which was diagnosed and evaluated by gastroscopy and was classified by the Los Angeles classification (grades A to D). Secondary endpoints included postoperative QOL, postoperative nutritional status, surgical safety, and postoperative recovery.

Statistical analysis

The expected incidence of reflux esophagitis after EG and DTR was about 31% and 8%, respectively(21). On the basis of that, a type I error of 5% and a power of 80%, 33 patients were needed in each group and assuming a dropout rate of 10%, 36 patients were needed in each group (total 72 patients).

The statistical analysis was performed with SPSS software (version 25.00.1; International Business Machines Corporation, Armonk, NY). For continuous variables, a test of normality was first performed. Normally distributed variables were presented as the mean ± standard deviation (SD), and differences between groups were analyzed using Student’s t test. Nonnormally distributed variables were presented as the median and the interquartile range, and a nonparametric test was applied to calculate the difference between groups. The chi-squared test and Fisher’s exact test (when appropriate) were adopted to compare categorical variables. Logistic regression was applied in multivariate analysis to determine the independent factors affecting reflux esophagitis. All values were two-tailed, and P values < 0.05 were regarded as statistically significant differences.

Patient characteristics

There were 98 patients initially screened for the study from January 2019 to May 2021, among whom 73 patients met the inclusion criteria and were enrolled in the trial, including 37 patients in the EG group and 36 in the DTR group. After one year of follow-up, 3 patients in the DTR group and 4 patients in the EG group were lost to follow-up (Figure 1). The baseline characteristics of the patients are shown in Table 1. No difference was observed regarding the patient demographics, including sex, age and BMI, and the tumor characteristics, including location, size, staging, and other pathology results, such as differentiation types, Lauren’s classification types, LVI and PNI, were similar between the two groups.

Surgical safety

With respect to surgical safety, there was no significant difference between the EG group and the DTR group, as shown in Table 2. The blood loss volume, postoperative complication rate and length of hospital stay were comparable between the EG and DTR groups. There was no grade III (Clavien–Dindo classification) complication in the EG group, while grade III complications of anastomotic leakage (1/36, 2.78%) and anastomotic bleeding (1/36, 2.78%) occurred in the DTR group. Meanwhile, the DTR group’s average operation time was significantly longer than that of the EG group, 221 minutes and 191 minutes, respectively (P=0.001). There was no reoperation or death within the two groups 30 days after surgery.

Reflux esophagitis

The incidence of reflux esophagitis 12 months after surgery, which was the primary endpoint of the trial, was significantly higher in the EG group than in the DTR group, that was, 32.4% and 8.3%, respectively (P=0.019). Moreover, reflux esophagitis was more severe in the EG group, in which the rates of grade A and grade B esophagitis were 24.3% and 8.1%, respectively. In contrast, within the DTR group, the incidence of grade A esophagitis was 8.3%, and no grade B esophagitis occurred, which was a significant difference. In univariate analysis, operation duration, blood loss volume and reconstruction method were associated with reflux esophagitis, while in the next step of multivariate analysis, it was demonstrated that only the reconstruction method was a significant factor affecting reflux esophagitis (P=0.049, Table 3).

Nutritional status

Nutritional status, including BMI, hemoglobin, serum albumin and serum total protein, demonstrated no significant difference between the EG and the DTR groups when evaluated at 3, 6 and 12 months after surgery (shown in Table 4 and Figure 2).

Quality of life

In general, the DTR group demonstrated a more favorable quality of life than the EG group as assessed by the EORTC QLQ-C30 (version 3.0) and the QLQ-STO22 questionnaire, as shown in Table 5 and Figure 3A-C. The average global health status (GHS) scores of the DTR group and the EG group were 83.3 and 50.0, respectively, which were significantly different (P<0.001). Among the functional scales, the DTR group’s emotional functioning (EF) score was significantly superior to that of the EG group, 70.8 and 50.0, respectively (P<0.001), while other scale scores, including physical functioning (PF), role functioning (RF), cognitive functioning (CF) and social functioning (SF), showed no difference. Regarding the symptoms scales, the EG group patients suffered more from symptoms such as fatigue (FA) (P<0.001), nausea and vomiting (NV) (P<0.001), pain (PAIN) (P<0.001), insomnia (SL) (P<0.001) and appetite loss (AP) (P<0.001), while other symptoms, including dyspnea (DY), constipation (CO) and diarrhea (DI), occurred evenly in the two groups. Financial difficulties (FI) were similar within the two groups.

In addition, other postoperative symptoms were evaluated in the EORTC QLQ-STO22 questionnaire as a specific module for gastric cancer patients. Symptoms such as dysphagia (DYS) (P<0.001), pain (PAIN) (P<0.001), reflux (RFX) (P<0.001), eating restrictions (EAT) (P=0.001), anxiety (ANX) (P<0.001), dry mouth (DM) (P=0.014), and taste change (TA) (P=0.013) occurred to a more serious degree in the EG group than in the DTR group, while aspects including body image (BI) and hair loss (HAIR) were the same in the two groups.

The number of upper-third gastric cancer patients has been increasing in East Asia, including China, Japan and Korea(12, 22-24). For patients meeting the criterion of radical proximal gastrectomy, PG is an organ-preserving surgery with several advantages over total gastrectomy(25, 26). However, the reconstruction method after PG has been controversial regarding prevention of reflux and improvement in QOL. Our study is the first prospective randomized controlled trial conducted to compare the incidence of reflux esophagitis, surgical safety, nutrition status and quality of life after EG or DTR in PG patients.

In the present study, the primary endpoint was the incidence of reflux esophagitis after surgery. The results demonstrated that the rate of reflux esophagitis was significantly lower in the DTR group than in the EG group (8.3% vs. 32.4%), and moreover, the severity of reflux esophagitis was much worse in the EG group, with 25% of the esophagitis patients classified as grade B, while none of the DTR group patients developed grade B reflux esophagitis according to the Los Angeles Classification of Gastroesophageal Reflux Disease. In other previous studies, it was demonstrated that the incidence of reflux esophagitis in the DTR group was significantly lower than that in the EG group (8-31.6% vs. 30.8-74%), which was consistent with our study(21, 27, 28). Moreover, in our study, it was proven in the multivariate analysis that the choice of reconstruction method was the only factor affecting the incidence of reflux esophagitis. The possible reason of DTR anti-reflux function might be that there is a 10-15 cm segment of jejunum interposed between the remnant stomach and the esophagojejunostomy and that, consequently, the gastric content rarely refluxes to the esophagus.

QOL is another important consideration when choosing a reconstruction method during organ-preserving gastrectomy, such as PG. It has been demonstrated that PG with DTR has QOL advantages over total gastrectomy in several previous studies(29, 30). However, few studies have focused on comparing the QOL of patients who have undergone EG or DTR after PG. In a retrospective study conducted by Eom et al., the QOL was balanced in the EG group and the DTR group, which was explained by the taking of proton-pump inhibitors to control reflux symptoms and the bias of retrospective research(31). In our study, patients who received DTR had superior results in several aspects of QOL, including global health status, emotional functioning and symptoms such as fatigue, nausea and vomiting, pain, insomnia, appetite loss, dysphagia, reflux, eating problems, anxiety, dry mouth and taste problems. Several studies have proven that gastroesophageal reflux disease impairs the health-related QOL of patients in all dimensions, both physically and psychologically(32-34), which is consistent with our results that DTR group patients had more favorable QOL on both functional scales and symptom scales because of a lower incidence of reflux esophagitis than EG group patients.

The advantage of EG reconstruction is that the operation procedure is much simpler, while three anastomoses are required during DTR(35). As a result, the operation time was significantly longer in the DTR group than in the EG group in this study. Nevertheless, the perioperative safety remained the same between the two groups, which was in accordance with previous studies(21, 31). In addition, Miyauchi et al. found that more anastomotic stenosis occurs in EG patients, which might be a result of fundoplication during esophagogastric anastomosis(27). Another advantage of EG reconstruction is that the physiological passage of food through the remnant stomach to the duodenum was entirely preserved, which enhances the absorption of nutrients, especially iron and vitamin B12(16). It has been reported that the passage of food into the remnant stomach is the critical factor that determines the postoperative nutritional status after DTR (36). In our study, the side-to-side gastrojejunostomy was performed using a 60 mm linear stapler rather than a circular stapler to ensure a sufficient width of the anastomosis so that food could enter the remnant stomach smoothly, which was a possible reason why the postoperative nutritional status was balanced in the DTR group and the EG group.

Our investigation was the first prospective randomized controlled study to compare the incidence of reflux esophagitis, surgical safety, nutritional status and QOL between EG and DTR after PG. Thus, the study was sufficiently powered for the analyses and the results. However, there were also several disadvantages of this study. First, it was a single-center study and compared with multi-center study, there might be some selection bias. Second, only one year of follow-up was performed, and some differences might not appear in such a limited time. Our next research step is to continue the follow-up and update the data in future articles.

DTR is superior to EG after PG in terms of the incidence of reflux esophagitis after surgery and provides a more satisfactory nutritional recovery and QOL regarding both functional scales and symptom scales without increasing surgical complications. Thus, DTR could be a favorable reconstruction method after PG.

GC: gastric cancer

EGJ: gastroesophageal junction

PG: proximal gastrectomy

QOL: quality of life

EG: esophagogastrostomy

DTR: double-tract reconstruction

JI: jejunal interposition

SD: standard deviation

GHS: global health status

EF: emotional functioning

PF: physical functioning

RF: role functioning

CF: cognitive functioning

SF: social functioning

FA: fatigue

NV: nausea and vomiting

PAIN: pain

SL: insomnia

AP: appetite loss

DY: dyspnea

CO: constipation

DI: diarrhea

FI: financial difficulties

DYS: dysphagia

RFX: reflux

EAT: eating restrictions

ANX: anxiety

DM: dry mouth

TA: taste change

BI: body image

HAIR: hair loss

Ethics approval and consent to participate

The study conformed to the Declaration of Helsinki and was approved by the Ethics Committee of Peking University Cancer Hospital (No. 2018KT97). All patients volunteered to participate and signed informed consent forms before enrollment.

Consent for publication

Not applicable.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

This study was funded by the Research Incubation Project, Beijing Municipal Administration of Hospitals (PX2019039). The funding was used in data collection and management.

Authors' contributions

Xin Ji and Zhaode Bu proposed the study concept.

Xin Ji, Yan Yan, Yinan Zhang and Zhaode Bu designed the study.

Xin Ji, Ziyu Jia, Heli Yang, Biao Fan, Anqiang Wang contributed to the data acquisition and management.

Yinan Zhang, Xin Ji and Yan Yan made the statistical analysis and interpretation of the results.

Yinan Zhang, Xin Ji and Yan Yan prepared the manuscript and the editing and reviewing.

Zhaode Bu finally approved the manuscript.

Acknowledgements

We thank the patients, their families, and all the investigators, nurses, and study team at Peking University Cancer Hospital. We also thank Beijing Municipal Administration of Hospitals for the funding of this research.

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Table 1. Clinical and pathological characteristics of the patients

Clinicopathological characteristics	EG (n=37)	DTR (n=36)	P value
Sex			0.515
Male	33 (89.2%)	30 (83.3%)
Female	4 (10.8%)	6 (16.7%)
Age (years)	64.6±10.0	64.8±9.0	0.865
BMI (kg/m2)	25.1±3.5	24.9±3.0	0.762
NACT			0.530
No	30 (81.1%)	27 (75.0%)
Yes	7 (18.9%)	9 (25.0%)
ACT			0.534
No	16 (43.2%)	13 (36.1%)
Yes	21 (56.8%)	23 (63.9%)
Borrmann type			0.681
EGC	14 (37.8%)	16 (44.4%)
I	0 (0%)	1 (2.8%)
II	7 (18.9%)	6 (16.7%)
III	16 (43.2%)	13 (36.1%)
Tumor size (cm)	3.1±1.4	2.7±1.1	0.187
pT stage			0.428
T1a	7 (18.9%)	5 (13.9%)
T1b	7 (18.9%)	11 (30.6%)
T2	7 (18.9%)	3 (8.3%)
T3	15 (40.5%)	14 (38.9%)
T4a	1 (2.7%)	3 (8.3%)
No. of harvested LNs	25.7±8.2	26.4±8.1	0.732
pN stage			0.325
N0	18 (48.6%)	25 (69.4%)
N1	7 (18.9%)	6 (16.7%)
N2	7 (18.9%)	2 (5.6%)
N3a	4 (10.8%)	2 (5.6%)
N3b	1 (2.7%)	1 (2.8%)
pTNM stage			0.510
Ia	5 (13.5%)	11 (30.6%)
Ib	6 (16.2%)	6 (16.7%)
IIa	15 (40.5%)	12 (33.3%)
IIb	5 (13.5%)	3 (8.3%)
IIIa	3 (8.1%)	1 (2.8%)
IIIb	3 (8.1%)	2 (5.6%)
IIIc	0 (0.0%)	1 (2.8%)
Tumor location			0.756
EGJ Siewert II	19 (51.4%)	21 (58.3%)
EGJ Siewert III	7 (18.9%)	7 (19.4%)
Upper	11 (29.7%)	8 (22.2%)
Differentiation			0.130
Well	2 (5.4%)	6 (16.7%)
Middle	22 (59.5%)	14 (38.9%)
Low	13 (35.1%)	16 (44.4%)
Lauren’s classification			0.513
Intestinal	25 (67.6%)	21 (58.3%)
Diffused	3 (8.1%)	6 (16.7%)
Mixed	9 (24.3%)	9 (25.0%)
LVI			0.401
No	19 (51.4%)	22 (61.1%)
Yes	18 (48.6%)	14 (38.9%)
PNI			0.373
No	22 (59.5%)	25 (69.4%)
Yes	15 (40.5%)	11 (30.6%)
Degree of LN dissection			0.200
D1/D1+	14 (37.8%)	19 (52.8%)
D2	23 (62.2%)	17 (47.2%)
Proximal margin (cm)	2.2±1.2	2.1±1.1	0.605
Distal margin (cm)	5.4±2.0	5.4±2.4	0.933

EG: esophagogastrostomy, DTR: double-tract reconstruction, BMI: body mass index, NACT: neoadjuvant chemotherapy, ACT: adjuvant chemotherapy, EGC: early gastric cancer, EGJ: gastroesophageal junction, LVI: lymphovascular invasion, PNI: peripheral nerve invasion, LN: lymph node

Table 2. Intraoperative and postoperative characteristics of the patients

Perioperative characteristics	EG (n=37)	DTR (n=36)	P value
Postoperative hospital stays (day)	11.0 (9.5-11.5)	11.5 (10.0-14.0)	0.058
Blood loss volume (ml)	50 (50-100)	50 (50-100)	0.415
Operation duration (min)	191 (173-219)	221 (200-257)	0.001
Postoperative complications			0.736
No	33 (89.2%)	31 (86.1%)
Yes	4 (10.8%)	5 (13.9%)
Clavien–Dindo classification
Grade I
Peritoneal effusion	0	1
Grade II
Anastomotic leakage	0	1
Gastrointestinal obstruction	1	1
Peritoneal effusion	2	1
Pulmonary infection	2	0
Anemia	1	0
Grade III
Anastomotic leakage	0	1
Anastomotic bleeding	0	1
Postoperative 30-day reoperation			>0.99
No	37	36
Yes	0	0
Postoperative 30-day death			>0.99
No	37	36
Yes	0	0
Reflux esophagitis			0.019
No	25 (67.6%)	33 (91.7%)
Yes	12 (32.4%)	3 (8.3%)
Los Angeles classification
A	9 (24.3%)	3 (8.3%)
B	3 (8.1%)	0 (0.0%)

EG: esophagogastrostomy, DTR: double-tract reconstruction

Table 3. Univariate analysis and multivariate logistic regression analysis of reflux esophagitis

Univariate analysis	P value	Multivariate analysis	OR (95% CI)	P value
Age	0.865	Reconstruction method		0.049
Gender	0.083	DTR	1
BMI	0.762	EG	4.416 (1.009-19.324)
Tumor location	0.096
Proximal margin	0.605
Distal margin	0.933
Differentiation	0.751
Lauren classification	0.964
Tumor size	0.187
pT stage	0.146
pN stage	0.823
pTNM stage	0.395
Number of harvested LNs	0.732
Degree of LND	0.898
LVI	0.804
PNI	0.691
NACT	0.618
Adjuvant chemotherapy	0.981
Operation duration	0.050
Blood loss volume	0.015
Postoperative hospital stays	0.480
Postoperative complication	0.454
Reconstruction method	0.019

BMI: body mass index, LN: lymph node, LND: lymph node dissection, LVI: lymphovascular invasion, PNI: peripheral nerve invasion, NACT: neoadjuvant chemotherapy, DTR: double-tract reconstruction, EG: esophagogastrostomy

Table 4. Postoperative nutritional status of the patients

Nutritional parameters	EG (n=37)	DTR(n=36)	P value
BMI (kg/m²)
Pre-operation	25.1±3.5	24.9±3.0	0.762
3 months post-operation	21.9±3.4	21.5±2.7	0.603
6 months post-operation	22.0±3.5	21.8±2.8	0.704
12 months post-operation	22.1±3.6	23.1±2.5	0.208
HGB (g/L)
Pre-operation	135.9±18.5	131.6±18.0	0.317
3 months post-operation	120.1±16.7	116.5±18.7	0.380
6 months post-operation	125.4±16.4	125.2±17.3	0.946
12 months post-operation	130.3±14.7	130.0±16.7	0.918
ALB (g/L)
Pre-operation	45.8±3.9	45.9±3.4	0.905
3 months post-operation	37.9±3.8	37.8±3.7	0.925
6 months post-operation	40.7±4.0	40.5±3.7	0.866
12 months post-operation	41.2±3.9	42.0±3.8	0.395
Total protein (g/L)
Pre-operation	70.8±5.2	72,2±5.7	0.285
3 months post-operation	61.1±4.2	60.7±4.6	0.685
6 months post-operation	64.5±4.1	64.4±4.9	0.962
12 months post-operation	64.6±3.9	66.0±4.5	0.156

DTR: double-tract reconstruction, EG: esophagogastrostomy, BMI: body mass index, HGB: hemoglobin, ALB: albumin

Table 5. The scores from the EORTC QLQ-C30 version 3.0 questionnaire and EORTC QLQ-STO22 questionnaire

Scales	EG, median (IQR)	DTR, median (IQR)	P value
EORTC QLQ-C30
Global health status	50.0 (33.3-50.0)	83.3 (66.7-83.3)	<0.001
Functional scales
Physical functioning	80.0 (66.7-83.3)	80.0 (66.7-86.7)	0.220
Role functioning	66.7 (66.7-66.7)	66.7 (66.7-83.3)	0.101
Emotional functioning	50.0 (41.7-62.5)	70.8 (66.7-83.3)	<0.001
Cognitive functioning	100.0 (66.7-100.0)	100.0 (70.8-100.0)	0.337
Social functioning	66.7 (66.7-66.7)	66.7 (66.7-83.3)	0.087
Symptom scales
Fatigue	33.3 (33.3-55.6)	33.3 (2.8-33.3)	<0.001
Nausea and vomiting	66.7 (50.0-83.3)	16.7 (16.7-16.7)	<0.001
Pain	33.0 (33.3-50.0)	8.3 (0.0-33.3)	<0.001
Dyspnea	0.0 (0.0-33.3)	0.0 (0.0-0.0)	0.182
Insomnia	33.3 (0.0-50.0)	0.0 (0.0-0.0)	<0.001
Appetite loss	33.3 (33.3-66.7)	0.0 (0.0-33.3)	<0.001
Constipation	0.0 (0.0-33.3)	0.0 (0.0-0.0)	0.097
Diarrhea	0.0 (0.0-33.3)	0.0 (0.0-0.0)	0.086
Financial difficulties	33.3 (0.0-33.3)	33.3 (0.0-33.3)	0.368
EORTC QLQ-STO22
Dysphagia	33.3 (22.2-44.4)	22.2 (11.1-22.2)	<0.001
Pain	41.7 (33.3-66.7)	25.0 (16.7-33.3)	<0.001
Reflux	88.9 (66.7-100.0)	33.3 (22.2-66.7)	<0.001
Eating restrictions	41.7 (33.3-66.7)	33.3 (25.0-47.9)	0.001
Anxiety	88.9 (66.7-100.0)	66.7 (47.2-75.0)	<0.001
Dry mouth	33.3 (33.3-66.7)	33.3 (0.0-33.3)	0.014
Taste	66.7 (33.3-66.7)	33.3 (0.0-66.7)	0.013
Body image	66.7 (66.7-100.0)	66.7 (66.7-100.0)	0.200
Hair loss	0.0 (0.0-0.0)	0.0 (0.0-25.0)	0.787

DTR: double-tract reconstruction, EG: esophagogastrostomy, IQR: interquartile range

No competing interests reported.

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Double-tract reconstruction is superior in controlling reflux esophagitis and enhancing quality of life after proximal gastrectomy: Results from a prospective randomized controlled clinical trial in China

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