Effect of double-tract reconstruction and laparoscopic proximal gastrectomy on immune function and stress

Abstract

BACKGROUND

Although surgery remains the primary treatment for proximal gastric cancer (PGC), ongoing refinements in surgical strategies are essential to improving clinical outcomes.

AIM

To investigate the effect of double-tract reconstruction (DTR) on immune function and stress response in patients undergoing laparoscopic proximal gastrectomy (LPG).

METHODS

In total, 78 patients with PGC admitted between August 2020 and August 2024 were enrolled. The research group consisted of 39 patients who underwent DTR + LPG, whereas the control group comprised 39 patients who underwent laparoscopic total gastrectomy with Roux-en-Y esophagojejunostomy. Perioperative indices (intraoperative blood loss, digestive tract anastomosis time, and time to first postoperative flatus), postoperative complications (intestinal obstruction, anastomotic ulcer, diarrhea, dumping syndrome, and gastroesophageal reflux), nutritional parameters (serum albumin, hemoglobin, and body mass index), immune function [immunoglobulin (Ig) G, IgA, and IgM), and stress response indicators (C-reactive protein, interleukin-6, and tumor necrosis factor-α) were collected and analyzed for both groups.

RESULTS

The intraoperative blood loss was lower (P < 0.05), and the time to first postoperative flatus time was shorter (P < 0.001) in the research group than in the control group. The two groups had comparable digestive tract anastomosis time (P > 0.05). The overall complication rate was significantly lower in the research group than in the control group (P = 0.042). Compared with the control group, the research group exhibited notably higher albumin, hemoglobin, and body mass index levels at 2 and 3 months postoperatively, as well as considerably high immunoglobulin (Ig) G, IgA, and IgM levels on postoperative day 1 (P < 0.05). The postoperative levels of C-reactive protein, interleukin-6, and tumor necrosis factor-α were also lower in the research group than in the control group (P < 0.001).

CONCLUSION

The combination of DTR and LPG in the treatment of patients with PGC is more effective in enhancing immune function and suppressing stress responses, showing more advantages over laparoscopic total gastrectomy.

Key Words: Double-tract reconstruction; Laparoscopic proximal gastrectomy; Immune function; Stress response; Clinical research

Core Tip: This study focused on patients with proximal gastric cancer (PGC), enrolling 78 cases to compare the clinical outcomes of two digestive reconstruction techniques: Double-tract reconstruction following laparoscopic proximal gastrectomy vs Roux-en-Y esophagojejunostomy following laparoscopic total gastrectomy, and optimize therapeutic strategies for PGC. The results demonstrate that double-tract reconstruction + laparoscopic proximal gastrectomy offers superior clinical benefits to laparoscopic total gastrectomy + Roux-en-Y reconstruction, including reduced intraoperative blood loss, a shorter time to first postoperative flatus (indicating faster postoperative recovery), enhanced safety, improved preservation of nutritional status and immune function, and a mitigated postoperative stress response. This study provides critical insights for refining surgical protocols in PGC management.

INTRODUCTION

Gastric cancer (GC) represents a malignant neoplasm associated with a substantial disease burden and a relatively high lethality rate[1]. Although global cancer statistics indicate a reduction in the incidence and mortality risk of GC, the disease still accounted for nearly 1.1 million newly diagnosed cases and a staggering 800000 fatalities in 2020[2]. Depending on the anatomical location of the tumor, GC is classified into proximal GC (PGC) and distal GC (DGC). In PGC, the tumor is located in the upper one-third of the stomach (including gastric cardia cancer and gastric fundus cancer), whereas in DGC, the tumor is situated in the lower one-third of the stomach[3,4].

The clinical manifestations of GC vary depending on the tumor location. Patients with PGC typically present with retrosternal pain and progressive dysphagia, whereas those with DGC commonly exhibit reflux, eructation, or nausea[5]. Xue et al[6] noted that, compared with patients with DGC, those with PGC exhibited lower 1-year, 3-year, and 5-year overall survival rates, implying that this subset of patients may have a poorer prognosis than those with DGC. This study focused on patients with PGC to optimize therapeutic approaches for PGC management.

Surgery remains the primary treatment modality for patients with PGC and is classified as either laparoscopic total gastrectomy (LTG) or laparoscopic proximal gastrectomy (LPG) based on the extent of resection[7]. Despite the enhanced efficacy of surgery in recent years, there remains substantial room for improvement[8].

This study aimed to conduct a comparative analysis between LTG + Roux-en-Y esophagojejunostomy and double-tract reconstruction (DTR) + LPG. LTG + Roux-en-Y esophagojejunostomy represents a commonly employed surgical approach with advantages such as lymph node dissection and anti-reflux properties. However, this approach also harbors potential drawbacks, including protracted operative duration, increased blood loss, and a heightened risk of postoperative complications[9,10]. LPG, though a simple procedure, disrupts the lower esophageal sphincter and cardia structures, often leading to adverse postoperative reactions such as acid reflux and heartburn[11]. In contrast, DTR + LPG can precisely prevent reflux and offer advantages in enhancing nutritional status and quality of life[12]. Following DTR + LPG, food can enter the distal digestive tract via the remnant stomach or jejunum, which not only mitigates esophageal reflux after proximal gastrectomy but also preserves the storage and digestive functions of the remnant stomach[13,14]. Kim and Kim[15] elucidated that DTR + LPG is more conducive to the absorption of iron and vitamin B12 and is beneficial for the prevention of reflux esophagitis compared with LTG. Studies investigating the effects of DTR + LPG on immune function and stress response in patients with PGC remain relatively limited. We believe that supplementing relevant analyses will further augment the potential biomedical applications of this technique.

MATERIALS AND METHODS

Patient information

Inclusion criteria: All patients were confirmed to meet the diagnostic criteria for LPG following preoperative endoscopic biopsy pathological examination and were classified as stage I or II according to the 8^th edition of the American Joint Committee on Cancer clinical staging system for GC. Preoperative imaging indicated that the lesions were located in the upper one-third of the stomach. All procedures were performed endoscopically, and the postoperative pathological diagnosis confirmed R0 resection. Patients had no contraindications for laparoscopic surgery and no history of abdominal surgery.

Exclusion criteria: Coexistence of other malignant tumors; pregnancy or lactation; presence of underlying diseases such as immune system diseases, coagulation disorders, and metabolic disorders; other types of GC that did not meet the indications for radical gastrectomy; severe cardiovascular, pulmonary, cerebral, and renal insufficiency and other diseases; and psychological ailments or mental disorders.

Based on these strict inclusion and exclusion criteria, 78 patients with PGC admitted to the Third Affiliated Hospital of Chengdu Medical College, Pidu District People’s Hospital, were meticulously screened and enrolled in the study. The enrollment period spanned from August 2020 to August 2024. Among them, 39 patients in the research group underwent DTR + LPG, whereas 39 in the control group underwent LTG + Roux-en-Y esophagojejunostomy. The hospital’s ethics committee approved this study without reservation. The intergroup comparison of general characteristics revealed no notable differences (P > 0.05), ensuring clinical comparability.

Methods

After admission, both groups underwent surgery performed by the same surgical team. The control group underwent LTG + Roux-en-Y esophagojejunostomy. After general anesthesia, the patient was placed in a supine position. Laparoscopic exploration was performed using the five-port method, the lymph nodes were cleaned, and the esophagus and gastric body were dissociated. Subsequently, a 5-cm incision was made in the midline of the upper abdomen. The duodenum was precisely transected at a site approximately 2 cm distal to the pylorus, and the lower esophagus was sutured approximately 3 cm from the cardia. Thereafter, the stomach and lower esophagus were ligated. An incision was then created on the right side of the esophagus above the ligation, and a small hole was made in the mesenteric margin of the jejunum approximately 30 cm from the ligament of Treitz. A side-to-side anastomosis was performed between the right end of the esophagus and proximal jejunum. The residual esophageal tissue was resected, and a side-to-side anastomosis of the jejunal Y-loop was performed approximately 40 cm from the jejunal anastomosis. Before completing these procedures, the bleeding condition was checked, and the common opening was closed.

The research group underwent DTR + LPG. The preoperative preparations and lymph node dissection procedures were identical to those implemented in the control group. For LPG, a 5-cm incision was made precisely in the midline of the upper abdomen to sever the esophagus. Subsequently, the proximal stomach was resected at a distance of 3 cm from the proximal tumor margin. For DTR, the jejunum and its mesenteric border were transected at a site 15 cm away from the ligament of Treitz, and the jejunum, colon, and esophageal stump were then anastomosed end-to-side. Thereafter, a side-to-side anastomosis between the remnant stomach and jejunum was performed at a distance ranging from 15 to 20 cm from the jejunoesophageal anastomosis site. In addition, the proximal and distal jejunum were anastomosed at a distance of approximately 30 cm from the remnant gastric-jejunal anastomosis site.

Evaluation indexes

Perioperative indices: Intraoperative blood loss, digestive tract anastomosis time, and time to the first postoperative flatus in both groups were thoroughly observed and documented.

Postoperative complications: The occurrence of side effects, such as intestinal obstruction, anastomotic ulcer, diarrhea, dumping syndrome, and gastroesophageal reflux, was monitored and recorded in both groups following treatment. The overall incidence rate was subsequently computed.

Nutritional parameters: Five milliliters of fasting venous blood was collected from patients in the early morning before surgery and 1, 2, and 3 months postoperatively. After centrifugation, the serum was procured to quantify serum albumin and hemoglobin (Hb) levels using an automatic biochemical analyzer. The body mass index (BMI) was also calculated.

Immune function: The levels of immunoglobulin (Ig) G, IgA, and IgM in the serum were quantified using an enzyme-linked immunosorbent assay before surgery and on postoperative day 1.

Stress response indicators: Fasting blood samples were drawn in the early morning before surgery and on postoperative days 1, 3, and 5 to detect C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor-α (TNF-α).

Statistical analysis

Measurement data were expressed as the mean ± SEM. Between-group comparison of measurement data was conducted using an independent sample t-test, whereas comparisons before and after treatment were performed using a paired t-test. The count data are presented as rates (percentage), and intergroup comparisons were conducted using a χ² test or Fisher’s exact probability test. The experimental data collected were analyzed with IBM SPSS Statistics version 20.0 (IBM Corp., Armonk, NY, United States). A P value < 0.05 indicated a significant difference.

RESULTS

General information

No significant difference in general information such as age, sex, tumor diameter, lymphatic vessel infiltration, differentiation grade, and pathological stage was identified between the research and control groups (P > 0.05) (Table 1).

Table 1 General information of two groups.

Indicators	Research group (n = 39)	Control group (n = 39)	t/χ2	P value
Age (years)	58.31 ± 7.30	55.69 ± 6.52	1.672	0.099
Sex (male/female)	12/27	18/21	1.950	0.163
Tumor diameter (cm)	2.33 ± 0.99	1.95 ± 0.68	1.976	0.052
Lymphatic vessel infiltration (positive/negative)	8/31	9/30	0.075	0.784
Differentiation degree (high differentiation/moderate-low differentiation)	6/33	5/34	0.106	0.745
Preoperative imaging staging (stage I/stage II)	5/34	4/35	0.126	0.723

Perioperative indices

Compared with the control group, the research group exhibited less intraoperative blood loss (P < 0.05), comparable digestive tract anastomosis time (P > 0.05), and shorter time to the first postoperative flatus (P < 0.001) (Table 2).

Table 2 Perioperative indices of two groups.

Indicators	Research group (n = 39)	Control group (n = 39)	t	P value
Intraoperative blood loss (mL)	219.03 ± 53.68	245.08 ± 38.65	2.459	0.016
Digestive tract anastomosis time (minutes)	30.08 ± 5.64	33.51 ± 9.44	1.948	0.055
Time to first postoperative anal exhaust (days)	2.44 ± 0.85	3.10 ± 0.79	3.552	< 0.001

Postoperative complications

The total complication incidence rate was significantly lower in the research group than in the control group based on the number of cases and incidence rates of intestinal obstruction, anastomotic ulcer, diarrhea, dumping syndrome, and gastroesophageal reflux (P = 0.042) (Table 3).

Table 3 Postoperative complications of two groups, n (%).

Indicators	Research group (n = 39)	Control group (n = 39)	χ2	P value
Intestinal obstruction	0 (0.00)	0 (0.00)
Anastomotic ulcer	0 (0.00)	0 (0.00)
Diarrhea	1 (2.56)	1 (2.56)
Dumping syndrome	0 (0.00)	4 (10.26)
Gastroesophageal reflux	1 (2.56)	3 (7.69)
Total	2 (5.13)	8 (20.51)	4.129	0.042

Nutritional parameters

Preoperative albumin, Hb, and BMI were not significantly different between the two groups (P > 0.05). At 1, 2, and 3 months postoperatively, all indices in both groups (except for Hb and BMI in the control group) exhibited an upward trend. Moreover, at 2 and 3 months after the surgery, all indices were remarkably higher in the research group than in the control group (P < 0.05) (Table 4 and Figure 1).

Figure 1 Nutritional parameters of the two groups. A: Pre- and postoperative albumin levels in the two groups; B: Pre- and postoperative hemoglobin levels in the two groups; C: Pre- and postoperative body mass index levels in the two groups. ^aP < 0.05 compared with preoperative; ^bP < 0.01 compared with preoperative; ^dP < 0.05 compared with control group. Alb: Albumin; Hb: Hemoglobin; BMI: Body mass index.

Table 4 Nutritional parameters of two groups.

Indicators	Research group (n = 39)	Control group (n = 39)	t	P value
Alb (g/L)
Before surgery	36.51 ± 4.23	35.49 ± 3.20	1.201	0.234
1 month after surgery	38.72 ± 3.68a	38.74 ± 2.41a	0.028	0.977
2 months after surgery	41.15 ± 2.95b	38.72 ± 2.99b	3.613	< 0.001
3 months after surgery	42.79 ± 3.18b	40.08 ± 3.14b	3.787	< 0.001
Hb (g/L)
Before surgery	129.08 ± 13.70	127.18 ± 13.31	0.621	0.536
1 month after surgery	131.56 ± 12.94	131.36 ± 13.13	0.068	0.946
2 months after surgery	134.21 ± 11.08	128.95 ± 7.39	2.466	0.016
3 months after surgery	135.87 ± 11.16a	130.41 ± 9.57	2.319	0.023
BMI (kg/m2)
Before surgery	21.69 ± 2.03	21.72 ± 1.70	0.071	0.944
1 month after surgery	21.72 ± 2.01	21.46 ± 1.96	0.578	0.565
2 months after surgery	22.62 ± 2.60	21.23 ± 1.46	2.911	0.005
3 months after surgery	23.05 ± 2.69a	20.15 ± 1.91b	5.489	< 0.001

^aP < 0.05, compared with before surgery.

^bP < 0.01, compared with before surgery.

Alb: Albumin; Hb: Hemoglobin; BMI: Body mass index.

Immune function

The two groups exhibited comparable preoperative IgG, IgA, and IgM levels (P > 0.05). Postoperatively, these indexes significantly decreased in both groups (P < 0.05); however, their levels remained higher in the research group than in the control group (P < 0.05) (Table 5 and Figure 2).

Figure 2 Immune functions of the two groups. A: Pre- and postoperative immunoglobulin (Ig) G levels in the two groups; B: Pre- and postoperative IgA levels in the two groups; C: Pre- and postoperative IgM levels in the two groups. ^bP < 0.01 compared with preoperative; ^dP < 0.05 compared with control group. IgG: Immunoglobulin G; IgA: Immunoglobulin A; IgM: Immunoglobulin M.

Table 5 Immune function of two groups.

Indicators	Research group (n = 39)	Control group (n = 39)	t	P value
IgG (g/L)
Before surgery	12.23 ± 1.72	11.97 ± 2.03	0.610	0.544
1 day after surgery	9.90 ± 1.68b	8.05 ± 2.28b	4.079	< 0.001
IgA (g/L)
Before surgery	3.12 ± 1.01	3.26 ± 1.10	0.585	0.560
1 day after surgery	1.87 ± 0.90b	1.38 ± 0.49b	2.986	0.004
IgM (g/L)
Before surgery	0.87 ± 0.30	0.97 ± 0.27	1.547	0.126
1 day after surgery	0.65 ± 0.25b	0.42 ± 0.17b	4.751	< 0.001

^bP < 0.01, compared with before surgery.

IgG: Immunoglobulin G; IgA: Immunoglobulin A; IgM: Immunoglobulin M.

Stress response

No significant differences were noted in the preoperative levels of CRP, IL-6, and TNF-α between the two groups (P > 0.05). On postoperative day 1, these indicators significantly increased in both groups. Subsequently, on postoperative days 3 and 5, both groups exhibited a gradual decline decrease in these indicators. In addition, all the indicators were considerably lower in the research group than in the control group at every time point postoperatively (P < 0.05) (Table 6 and Figure 3).

Figure 3 Stress responses of the two groups. A: Pre- and postoperative C-reactive protein levels in the two groups; B: Pre- and postoperative interleukin-6 levels in the two groups. C: Pre- and postoperative tumor necrosis factor-α levels in the two groups. ^bP < 0.01 compared with preoperative; ^cP < 0.001 compared with preoperative; ^dP < 0.05 compared with control group. CRP: C-reactive protein; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-α.

Table 6 Stress response of two groups.

Indicators	Research group (n = 39)	Control group (n = 39)	t	P value
CRP (ng/mL)
Before surgery	3.05 ± 0.69	2.95 ± 0.65	0.659	0.512
1 day after surgery	86.64 ± 10.66c	103.67 ± 12.71c	6.411	< 0.001
3 days after surgery	64.36 ± 5.86b	87.33 ± 8.58b	13.806	< 0.001
5 days after surgery	21.77 ± 2.92b	38.92 ± 3.72b	22.647	< 0.001
IL-6 (pg/mL)
Before surgery	78.33 ± 6.69	81.05 ± 6.39	1.836	0.070
1 day after surgery	310.77 ± 38.79c	398.13 ± 45.78c	9.092	< 0.001
3 days after surgery	238.00 ± 18.60c	332.64 ± 45.73c	11.972	< 0.001
5 days after surgery	106.97 ± 12.24b	201.36 ± 17.14b	27.988	< 0.001
TNF-α (ng/mL)
Before surgery	43.08 ± 7.19	45.44 ± 5.70	1.606	0.112
1 day after surgery	134.85 ± 20.56c	163.03 ± 22.68c	5.749	< 0.001
3 days after surgery	107.92 ± 11.51b	153.54 ± 20.08b	12.309	< 0.001
5 days after surgery	66.72 ± 10.45b	83.74 ± 10.45b	7.192	< 0.001

^bP < 0.01, compared with before surgery.

^cP < 0.001, compared with before surgery.

CRP: C-reactive protein; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-α.

DISCUSSION

DTR + LPG demonstrated remarkable clinical advantages by reducing intraoperative blood loss and facilitating a quicker onset of the first postoperative flatus without affecting the time required for digestive tract anastomosis. This finding suggests that DTR + LPG confers significant clinical benefits in curtailing intraoperative blood loss and hastening the time to the first postoperative flatus in such patients.

In the study by Sun et al[16], performing DTR + LPG in patients with PGC and those with adenocarcinoma of the esophagogastric junction resulted in minimal blood loss without substantially extending operative time, which is consistent with the results of the present study. Xiao et al[17] reported that patients with PGC who underwent DTR + LPG experienced significantly shorter times to first postoperative flatus and postoperative hospitalization, corroborating our observations. DTR involves placing a jejunal segment between the esophagus and the remnant stomach. This not only preserves partial gastric function but also prevents severe postoperative gastroesophageal reflux[18]. With this technique, food reaches the jejunum directly and mixes thoroughly with bile, expediting the emptying of food in the remnant stomach and effectively curtailing the time to the first postoperative flatus[19].

From a safety perspective, the control group predominantly exhibited dumping syndrome (10.26%), followed by gastroesophageal reflux (7.69%) and diarrhea (2.56%). Conversely, the research group primarily presented with diarrhea (2.56%) and gastroesophageal reflux (2.56%), which was consistent with the findings of Hirata et al[20]. DTR + LPG proves to be more advantageous in reducing the overall incidence of postoperative complications among patients with PGC. This could be ascribed to the buffering effect of DTR on food, which aids in alleviating the stimulation of the gastric antrum by food and in circumventing gastric emptying impairments. This is conducive to mitigating the risks associated with gastroesophageal reflux and dumping syndrome[21].

As regards nutritional parameters, DTR + LPG more effectively improves the nutritional status of patients with PGC. After DTR + LPG, the duodenum and distal stomach are preserved, allowing food to enter the distal gastric cavity and distal jejunum through the esophagojejunostomy. This promotes full contact between food and digestive juices, thereby actively regulating gastrointestinal function and gastric hormone secretion and enhancing the postoperative nutritional status of patients[22]. The DTR + LPG technique is superior to LTG in preventing vitamin B12 deficiency among patients with early GC, implying that patients undergoing DTR + LPG intervention may experience better nutritional outcomes[23]. Wang et al[24] reported that patients with PGC who underwent DTR + LPG experienced fewer reflux symptoms and had higher BMI levels than those who underwent LTG + Roux-en-Y esophagojejunostomy, which concurs with the findings of the present study.

With regard to immune function, DTR + LPG has a relatively less pronounced effect on the immune function of patients with PGC. In terms of stress indexes, DTR + LPG exerts a relatively limited influence on CRP, IL-6, and TNF-α levels in patients with PGC, indicating that DTR + LPG contributes to a milder postoperative stress response and a more rapid recovery process. CRP, an acute-phase protein, is rapidly synthesized and secreted into the bloodstream by the liver following stress stimuli such as infection, inflammation, tissue injury, surgical trauma, and myocardial infarction. Elevated CRP levels are indicative of the body’s stress response. Similarly, IL-6, a versatile cytokine intimately associated with the advancement of inflammation, surges promptly in the face of stress triggers like infection, trauma, and ischemia, marking it as an early stress response indicator. Meanwhile, TNF-α, which is swiftly generated and discharged by immune cells upon encountering stress stimuli including infection, ischemia, and trauma, also denotes the body’s stress condition when found in elevated concentrations[25,26]. Consequently, this study evaluated the stress status of patients subjected to the two treatment approaches by monitoring these specific biomarkers. DTR + LPG helps reduce patient reflux symptoms, improve their nutritional status, preserve the function of the pylorus, decrease surgical trauma, and lower the risk of postoperative complications. These factors help minimize the effect on immune function and stress responses[27,28].

Numerous researchers have extensively explored and clinically analyzed various alternative treatment approaches. For instance, Huang et al[29] pointed out that the double-flap technique, when compared with DTR in patients with PGC, can result in a more significant improvement in postoperative nutritional status. However, it has higher requirements and is more time-consuming. Likewise, Yang et al[30] indicated that double-tract anastomosis and esophagogastric anastomosis in patients who underwent LPG could relieve the postoperative esophageal reflux symptoms more effectively and improve short-term nutritional status. Furthermore, Zhang et al[31] noted that a side overlap with fundoplication by the Yamashita technique performed in patients who underwent LPG further promoted postoperative recovery in terms of weight and eating function compared with LTG + Roux-en-Y esophagojejunostomy. Nevertheless, it also entailed a relatively high risk of postoperative reflux.

This study has some limitations that warrant further investigation. First, the time points for measuring immune function data are limited; immune parameters were evaluated only preoperatively and on postoperative day 1. To comprehensively assess the dynamic effect of surgical strategies on immune homeostasis, future studies should incorporate longitudinal data to clarify the temporal relationship between immune recovery and clinical outcomes. Second, as a single-center study with a modest sample size, the conclusions were derived from a single-center cohort of 78 patients. In subsequent analyses, analyzing clinical records of a wider range of patients from multiple centers will enhance the generalizability of the research results. Subsequent research efforts will be centered on these aspects to enhance the quality and scope of the study.

CONCLUSION

Compared with patients with PGC who underwent LTG + Roux-en-Y esophagojejunostomy, those who underwent DTR + LPG exhibited reduced intraoperative blood loss, shorter time to the first postoperative flatus, enhanced safety, remarkably improved nutritional status and immune function, and a milder postoperative stress response.