DOI: https://doi.org/10.21203/rs.3.rs-2392046/v1
With the popularity of function-preserving gastrectomy(FPG) and minimally invasive surgery, proximal gastrectomy(PG) has been widely used in the upper third gastric cancer. There are many reconstruction methods after PG, but the optimal one is still uncertain. The aim of this study is to compare the short-term and long-term outcomes of double-tract reconstruction(DT) and gastric tube reconstruction(Tube) after proximal gastrectomy.
This study retrospectively reviewed patients who underwent gastrectomy from January 2010 to January 2022 in our hospital. According to the reconstruction method after PG, patients were divided into DT group and Tube group. After adjusting for propensity score matching analysis, we compared the surgical outcomes, complications, and postoperative long-term reflux esophagitis and nutritional status between the two groups.
After propensity score matching had been done, a total of 44 patients were included in this analysis (22 patients in the Tube and DT groups respectively). There were no significance between the two groups in postoperative complications, days of postoperative hospital stay, hemoglobin and albumin decreasing rate at 6 months, and weight loss at 6 and 12 months. The operation time of Tube group was shorter (230 vs 290 min, p = 0.005). The visick score (p = 0.012) and the rate of endoscopic reflux esophagitis (p = 0.001) of DT group were significantly lower .
There is no significance in postoperative complications and nutritional status between double-tract and gastric tube reconstruction after PG. Tube reconstruction can greatly reduce the operation time, while double-tract is more effective in preventing postoperative esophageal reflux.
Gastric cancer is the fifth most common malignant tumor and the fourth leading cause of cancer death worldwide[1]. The incidence of upper third gastric cancer is on the rise,the latest national gastric cancer statistics in Korea showed that the incidence increased from 11.2% in 1995 to 20.9% in 2019, and the incidence of early gastric cancer also increased from 28.6–63.6%[2]. For upper third gastric cancer, proximal gastrectomy(PG) can be performed when more than half of the stomach is reserved under the premise of tumor safety [3]. With the popularity of function-preserving gastrectomy(FPG) and minimally invasive surgery in recent years, more and more surgeons choose PG other than total gastrectomy(TG) in upper third gastric cancer. While there are many reconstruction methods after PG, including esophagogastrostomy(EG), jejunal interposition(JI) and double-tract(DT). Traditional EG will easily lead to esophageal reflux because anti-reflux structures such as cardia, fundus and HIS Angle are destroyed[4]. At present, EG is performed usually with some anti-reflux procedures, including gastric tube reconstruction[5], double flap[6], side overlap[7], fundoplication[8] and rebuild of fundus and HIS Angle[9, 10]. However, the optimal reconstruction method remains uncertain[11]. In this study, we compared DT and gastric tube reconstruction, which is most commonly carried out after PG in our institution, to clarify the surgical outcomes and postoperative long-term effects of DT and gastric tube reconstruction.
We retrospectively collected data from consecutive patients with gastric cancer who had undergone gastrectomy at our hospital between January 2010 and December 2022. Exclusion criteria including total gastrectomy, distal gastrectomy, non-curative surgery, tumor surgery other than adenocarcinoma, surgery with insufficient postoperative data, and surgery with other reconstruction methods after PG. Eligible patients were divided into gastric tube reconstruction(Tube group) and double-tract reconstruction(DT group). the study was approved by the Ethics Committee of the Second Affiliated Hospital of Nanjing Medical University for the research purpose use of the data.
All patients underwent PG and regional lymphadenectomy according to the Japanese gastric cancer treatment Guidelines, 5th edition[12]. After routine abdominal exploration showed no peritoneal implantation and distant metastasis, PG with D1 + lymph node dissection was performed, dissection including Nos. 1, 2, 3a, 4sa, 4sb, 7,8a, 9, 11p. After lymph node dissection was finished, the distal stomach was cut off from the greater curvature of the middle part of the gastric body to the lesser curvature of the gastric antrum with a linear stapler, the esophagus was cut off 2cm above the cardia, the jejunum was cut off 20cm below the Treitz ,and the distal jejunum was lifted up and anastomosed with the esophagus using a circular stapler, the remnant stomach and jejunum were anastomosed 10–15 cm below the esophagogastrostomy with a linear stapler. A side-to-side anastomosis of the proximal and distal jejunum was performed 25 to 30 cm below the gastrojejunostomy, and the double-tract reconstruction was completed (Fig. 1.a).
In gastric tube reconstruction, after lymph node dissection was finished, the esophagus was cut off 2cm above the cardia, the gastric tissue was cut off parallel to the greater curvature of the stomach from the lesser curvature of the stomach with a linear stapler, so that the remnant stomach forms a tube with a length of 20cm and a width of 3-4cm, the esophagogastrostomy is performed at a distance of 5cm from the gastric stump using a circular stapler, and the gastric tube reconstruction was completed (Fig. 1.b). The hepatic branch of the vagus nerve was preserved in both groups to prevent gastric emptying Dysfunction after surgery.
Propensity score matching analysis was performed by using R 4.0.5 software to balance variables including age, sex, body mass index (BMI), nutritional risk score(NRS), American Society of Anesthesiologists physical status (ASA-PS), tumor location, cT stage. These two groups were matched at a ratio of 1 :1, the propensity score was estimated using a logistic regression model through greedy matching without replacement by using a caliper value of 0.02. Pearson’s chi-square test was used for categorical variables, and Mann-Whitney U test was used for continuous variables and grade data to analyze the differences in surgical outcomes and postoperative long-term efficacy between the Tube group and DT group. The continuous data were expressed as median with Standard deviation or range,All statistical comparisons were two-sided, and P < 0.05 was considered statistically significant. All statistical analyses were performed by using SPSS 25.0 software (SPSS, USA) .
A total of 1496 patients who underwent gastrectomy were identified in the database. After exclusion criteria were applied, 129 patients were enrolled in the study, including 104 patients with gastric tube reconstruction and 25 patients with double-tract reconstruction,there were significant differences between these two groups in tumor location (p = 0.039) and cT stage (p = 0.02). After propensity matching, 44 patients were included in the study (22 each for the Tube and DT groups),The distribution of propensity scores was similar between the groups(Fig. 2.), and no significance were found in clinical characteristics between the Tube and DT groups after matching(Table 1.). A flowchart is shown in Fig. 3.
| Before matching | After matching | |||||
|---|---|---|---|---|---|---|
| Tube (n = 104) | DT (n = 25) | p | Tube (n = 22) | DT (n = 22) | p | |
| Age(year, mean ± SD) | 64.6 ± 11.3 | 65.8 ± 11.6 | 0.433 | 68.8 ± 7.4 | 64.9 ± 12.0 | 0.341 |
| Sex | 0.256 | 1.0 | ||||
| Male | 76 (73.1%) | 21 (84%) | 18 (81.8%) | 18 (81.8%) | ||
| Female | 28 (26.9%) | 4 (16%) | 4 (18.2%) | 4 (18.2%) | ||
| BMI (kg/m2 ,mean ± SD) | 21.5 ± 2.2 | 22.0 ± 2.3 | 0.192 | 20.7 ± 2.0 | 22.0 ± 2.4 | 0.052 |
| NRS(mean ± SD) | 2.9 ± 1.1 | 2.8 ± 1.1 | 0.415 | 3.1 ± 1.2 | 2.7 ± 1.1 | 0.144 |
| ASA-PS | 0.634 | 0.296 | ||||
| 1–2 | 83 (79.8%) | 21 (84%) | 15 (68.2%) | 18 (81.8%) | ||
| ≥ 3 | 21 (20.2%) | 4 (16%) | 7 (31.8%) | 4 (18.2%) | ||
| Siewert | 0.039 | 1.0 | ||||
| II | 35 (33.7%) | 14 (56%) | 11 (50%) | 11 (50%) | ||
| III | 69 (66.3%) | 11 (44%) | 11 (50%) | 11 (50%) | ||
| cT | 0.02 | 0.350 | ||||
| cT1a(M) | 28 (26.9%) | 13 (52%) | 12 (54.6%) | 10 (45.4%) | ||
| cT1b(SM) | 65 (62.5%) | 8 (32%) | 9 (4.9%) | 8 (36.4%) | ||
| cT2(MP) | 11 (10.6%) | 4 (16%) | 1 (4.5%) | 4 (18.2%) | ||
| Remedial surgery after ESD | 20 (19.2%) | 7 (28%) | 0.333 | 5 (22.7%) | 5 (22.7%) | 1.0 |
Surgical outcomes was showed in Table 2. After matching, operation time was significantly shorter in the Tube group than in the DT group (230 vs 290min, p = 0.005). Postoperative hospital stay and postoperative complications were similar between the two groups, with complication rates of 13.6% in the Tube and 18.2% in the DT group (p = 0.646).
| After matching | |||
|---|---|---|---|
| Tube (n = 22) | DT(n = 22) | p | |
| operation time (min) Median (range) | 230(200–360) | 290(200–500) | 0.005 |
| Blood loss (ml) Median (range) | 230(100–500) | 200(100–500) | 0.461 |
| first fluid time after surgery (days) | 3(2–9) | 3.5(2–7) | 0.095 |
| Hospital stay after surgery (days) | 10.5(8–21) | 10(6–21) | 0.414 |
| Histological type | 0.434 | ||
| Differentiated type | 17 | 19 | |
| Undifferentiated type | 5 | 3 | |
| harvested lymph nodes (mean ± SD) | 25.77 ± 4.30 | 28.82 ± 10.10 | 0.217 |
| positive lymph nodes (mean ± SD) | 0.14 ± 0.35 | 0.55 ± 0.96 | 0.12 |
| Complication | |||
| Anastomotic bleeding | 2 | 2 | |
| Anastomotic stenosis | 0 | 1 | |
| Anastomotic leak | 1 | 1 | |
| Clavien–Dindo ≥ III | 0 | 0 | |
| Total complications | 3(13.6%) | 4(18.2%) | 0.646 |
Postoperative long-term outcomes in Nutritional Status and reflux esophagitis.
Comparison of postoperative long-term outcomes between the Tube and DT groups before and after matching was showed in Table 3. There was no significant difference in the rate of decreasing in hemoglobin and albumin at 6 months after surgery and weight loss between the two groups at 6 and 12 months after surgery. At 12 months after surgery, the incidence of endoscopic reflux esophagitis (P = 0.001) and visick score (p = 0.012) were higher in the Tube group than in the DT group.
| Before matching | After matching | |||||
|---|---|---|---|---|---|---|
| Tube (n = 104) | DT (n = 25) | p | Tube (n = 22) | DT (n = 22) | p | |
| Post/preoperative Hb in 6M | 94.9 ± 4.9 | 95.3 ± 9.5 | 0.106 | 96.0 ± 6.2 | 95.6 ± 10.1 | 0.209 |
| Post/preoperative Alb in 6M | 93.6 ± 9.5 | 94.9 ± 6.6 | 0.938 | 94.1 ± 4.5 | 95.0 ± 6.9 | 0.725 |
| Weight loss in 6M | 11.2 ± 3.1 | 10.5 ± 3.7 | 0.506 | 11.1 ± 4.2 | 10.5 ± 3.7 | 0.518 |
| Weight loss in 12M | 7.1 ± 4.5 | 7.9 ± 5.3 | 0.333 | 7.1 ± 5.2 | 7.8 ± 5.5 | 0.672 |
| Endoscopic reflux esophagitis in 12M by Los Angeles classifification | 0.002 | 0.001 | ||||
| A | 37(35.6%) | 3(12%) | 5(22.7%) | 2(9.0%) | ||
| B | 14(13.5%) | 2(8%) | 3(13.6%) | 2(9.0%) | ||
| C | 12(11.5%) | 1(4%) | 5(22.7%) | 1 (4.5%) | ||
| D | 6(5.8%) | 0 | 1(4.5%) | 0 | ||
| Visick score | 0.021 | 0.012 | ||||
| 1 | 33(31.7%) | 16(64%) | 8(36.4%) | 15(68.2%) | ||
| 2 | 41(39.4%) | 6(24%) | 6(27.3%) | 4(18.2%) | ||
| 3 | 19(18.3%) | 3(12%) | 5(22.7%) | 3(13.6%) | ||
| 4 | 11(10.6%) | 0 | 3(13.6%) | 0 | ||
In recent years, the incidence of upper third gastric cancer has gradually increased, and PG has been used more and more, whether laparoscopic surgery, open surgery or robotic surgery[2]. PG is a kind of function-preserving gastrectomy[13]. The remnant stomach has the function of storing and digesting food, which can increase food intake and improve postoperative nutritional status[14, 15]. Gastric acid and intrinsic factors secreted by the remnant stomach can preventing anemia and vitamin B12 deficiency, and the pylorus can slow down the food emptying, making blood glucose levels more stable[16–18]. When performing PG, more than half of the distal stomach needs to be preserved to ensure that the remnant stomach is functional after surgery[19]. Routine dissection of distal perigastric nodes Nos.4d, 5, 6 is not required when D1 + lymph node dissection is performed. Yura[20] et al. reported a pathological study of 202 patients with T2/T3 proximal gastric cancer who underwent TG showed that The metastatic rates at Nos.4d and Nos.12a were very low (0.99% and 0.006%, respectively), and those at Nos.5 and Nos.6 were zero. Therefore, PG with D1 + lymph node dissection for proximal early gastric cancer is an oncologically safe option[21]. There is no absolute requirement for preservation of the vagus nerve[22], but when the vagus nerve around the esophagus is cut, it may cause pyloric spasm and dysfunction[14], and preservation of the hepatic branch of the vagus nerve helps to reduce the occurrence of delayed gastric emptying[23]. Common reconstruction methods after PG include esophagogastrostomy(EG), jejunal interposition(JI) and double-tract(DT)[11, 24]. EG lacks anti-reflux structure, so postoperative esophageal reflux is very high. Miyauchi[4] et al. showed that the reflux rate of EG was as high as 74% (n = 23). Therefore, EG is usually accompanied by anti-reflux procedures, including gastric tube reconstruction, double-flap, side overlap, fundoplication, and rebuild of fundus and HIS Angle. Gastric tube reconstruction reduces the amount of acid-secreting gastric tissue, and an artificial fundus structure above the anastomosis can cushion acid reflux[25]. A comparative study by Chen showed a reflux rate of 11.8% (n = 34) with gastric tube reconstruction[26]. The anti-reflux effect of JI and DT is achieved by inserting a segment of jejunum between the esophagus and the remnant stomach[27, 28], and DT has remnant stomach passage and jejunum passage, which can increase food intake and improve postoperative nutritional status[29]. Tanaka[30] et al. thought that when most food intake pass through the jejunum passage rather than remnant stomach passage,the effect of DT will be similar to TG. Kamiya[31] et al. used the Post-Gastrectomy Syndrome Assessment Scale-45 (PGSAS-45) to investigate 172 patients after DT and found that patients with a larger remnant stomach, a shorter interposition jejunal length (≤ 10 cm), and a bigger size of gastrojejunostomy (> 6 cm) had higher postoperative QOL scores. In this study, we used a Propensity Score Matching to reduce any treatment selection bias and potential confounding[32], we found that DT had a longer operation time than Tube, but there was no increase rate in postoperative complications, It shows that DT is a safe operation, while for some patients who cannot tolerate long surgery, we can try to choose Tube. There was no significant difference in nutritional status between DT and Tube groups. Nomura[16] et al. showed that the weight loss in 12 month after TG was 16.2%, while in our study, the weight loss in 12 month after DT and Tube was 7.1%-7.8%, indicating that the preservation of the stomach has certain advantages over TG. In terms of anti-reflux, although gastric tube reconstruction added anti-reflux structures, compared with DT, endoscopic reflux esophagitis and visick score were higher, and the incidence of reflux ≥ grade B was 40.8% vs 13.5% (p = 0.001), visick score ≥ 3 was 36.3% vs 13.6% (p = 0.012). The effects of EG with other antireflux procedures also need to be studied furthermore.
This study had some limitations. First, this is a single-center retrospective study, and some patients with DT or gastric tube reconstruction after PG were not included in this study due to lack of follow-up data, which will lead to a choosing bias on our propensity score matching. Secondly, the majority of surgeons are not as skilled with DT as with gastric tube reconstruction, thus prolonging his operation time in DT.
There is no significant difference in postoperative complications and nutritional status between double-tract and gastric tube reconstruction in PG. Tube can greatly reduce the operation time, while DT is more effective in preventing postoperative esophageal reflux.
Authors’ contributions Statement
lai chuilin,gu qiou and zhan tian wrote the main manuscript text. guan xiao,lu na and jia heng prepared figures and tables. zhang jianping revised the manuscript. All authors reviewed the manuscript.
Funding: National Natural Science Foundation (Grant Number: 81874058 to Jian-Ping Zhang)
Ethics of this study was approved by the Ethics Committee of the Second Affiliated Hospital of Nanjing Medical University for the research purpose use of the data.