Control observation of different digestive tract reconstruction methods in total gastrectomy for gastric cancer

Abstract

BACKGROUND

For patients with advanced gastric cancer, surgical resection remains the main treatment option. Total gastrectomy combined with radical resection of gastric cancer lesions and sentinel lymph nodes can significantly prolong the survival of patients. Digestive tract reconstruction after total gastrectomy is essential to maintain gastrointestinal function and optimize postoperative recovery. Therefore, it is very important to choose a suitable reconstruction method to improve the quality of life of total gastrectomy patients.

AIM

To evaluate the effects of different digestive tract reconstruction methods in gastric cancer patients undergoing total gastrectomy.

METHODS

This retrospective study included 172 patients who underwent total gastrectomy for gastric cancer at The First Hospital of Hebei Medical University for analysis. The patients were categorized into two groups: Group A, consisting of 90 patients who underwent modified Roux-en-Y gastrojejunostomy, and group B, consisting of 82 patients who underwent uncut Roux-en-Y gastrojejunostomy. The general patient characteristics, perioperative indicators, postoperative gastrointestinal mucosal barrier function, nutritional status, immunological markers, and occurrence of complications were compared between the two groups.

RESULTS

Group A showed shorter digestive tract reconstruction time than group B (P < 0.05). On the first postoperative day, group A showed lower serum levels of D-lactate, diamine oxidase, and endotoxin than group B (P < 0.05). One month postoperatively, group A showed higher prognostic nutritional index, serum albumin, total protein, and body weight than group B (P < 0.05). One month postoperatively, the levels of cluster of differentiation (CD) 3 +, CD4 +, and CD8 + cells were not significantly different between two groups (P > 0.05). The complication rates were 10.00% in group A and 24.39% in group B; group A had a significantly lower complication rate than group B (P < 0.05).

CONCLUSION

Using modified Roux-en-Y gastrojejunostomy during total gastrectomy shortens the time required for gastrointestinal anastomosis, reduces surgery-induced gastrointestinal mucosal damage, and mitigates postoperative declines in nutritional status.

Key Words: Total gastrectomy; Digestive tract reconstruction; Gastric cancer; Gastrointestinal barrier; Immune function; Safety

Core Tip: Total gastrectomy combined with radical resection of gastric cancer lesions and sentinel lymph nodes can significantly prolong the survival of patients. Postoperative digestive tract reconstruction is crucial to maintain gastrointestinal function and optimize postoperative recovery. This study found that the application of modified Roux-en-Y gastrojejunostomy in total gastrectomy shortened the gastrointestinal anastomosis time, reduced the gastrointestinal mucosal injury caused by the operation, and alleviated the decline in postoperative nutritional status. This approach also reduces the overall incidence of surgical complications.

INTRODUCTION

Gastric cancer is a prevalent malignant tumor, with over one million new cases reported worldwide each year and approximately 800000 deaths attributed to the disease[1,2]. In clinical practice, chemotherapy and radiotherapy are commonly used as adjuvant treatments, often employed as neoadjuvant therapy before and after surgery, as well as for some advanced-stage patients who are unsuitable candidates for surgery. However, surgical resection remains the primary treatment modality[3]. Studies have shown that total gastrectomy with radical resection of gastric cancer lesions and sentinel lymph nodes can significantly prolong patient survival[4]. The method of digestive tract reconstruction following total gastrectomy is crucial for maintaining gastrointestinal function and optimizing postoperative recovery. Therefore, selecting an appropriate reconstruction method is crucial for improving the quality of life of patients undergoing total gastrectomy. Modified and uncut Roux-en-Y anastomoses are commonly used techniques for digestive tract reconstruction following this procedure. The modified Roux-en-Y anastomosis involves connecting the distal jejunum to the esophagus and joining the proximal jejunum to the distal jejunum to form a Y-shaped structure, which provides an enhanced anti-reflux effect[5]. Uncut Roux-en-Y anastomosis utilizes a special clamp on the Roux limb to keep it intact, creating a functional bypass that preserves normal intestinal motility and reduces the risk of blind loop syndrome[6]. This study investigated the impact of these two digestive tract reconstruction methods on gastrointestinal barrier function, immune function, and safety in patients with gastric cancer undergoing total gastrectomy, with the aim of providing a basis for optimizing surgical treatment strategies.

MATERIALS AND METHODS

General data

This retrospective study included 172 patients who underwent total gastrectomy for gastric cancer at The First Hospital of Hebei Medical University over the past four years. Based on the type of digestive tract reconstruction, the patients were categorized into two groups: Group A consisted of 90 patients who underwent modified Roux-en-Y gastrojejunostomy, and group B consisted of 82 patients who underwent uncut Roux-en-Y gastrojejunostomy. The selection period for the patients was from April 2020 to April 2024. This study was approved by the Ethics Committee of The First Hospital of Hebei Medical University (approval No. 20220651). The inclusion and exclusion criteria for the study subjects are as follows.

Diagnostic criteria: The diagnostic criteria for gastric cancer patients included in the study were based on the standards outlined in the “2018 Guidelines for the Diagnosis and Treatment of Gastric Cancer”[7]. Patients were diagnosed using gastrointestinal endoscopy, and the diagnosis was further confirmed postoperatively through frozen pathological sections and immunohistochemical examinations.

Inclusion criteria: (1) Patient age range: 18-75 years; (2) Pathological staging of gastric cancer ≤ stage III, with no metastasis to distant organs or sites; (3) Preoperative performance status for gastric cancer patients assessed by the Karnofsky performance status score[8] ≥ 65, and Eastern Cooperative Oncology Group score[9] ≤ 2; (4) All patients were newly diagnosed with gastric cancer and had not received radiotherapy, chemotherapy, or immunotherapy before surgery; (5) Preoperative surgical safety assessment confirmed that patients had adequate coagulation, cardiovascular function, and respiratory function to tolerate surgery; and (6) Informed consent was obtained from all patients prior to surgery.

Exclusion criteria: (1) Patients with gastric patients and distant metastasis; (2) Patients with recurrent gastric cancer who previously underwent gastric cancer surgery; (3) Patients with stomach metastases from malignant tumors originating at other sites; (4) Patients with gastrointestinal perforation or extensive intra-abdominal infection; and (5) Patients with concomitant immunological diseases.

Surgery methods

Group A: Modified Roux-en-Y anastomosis. An appropriately sized stapler base was selected and positioned approximately 65 cm-70 cm from the ligament of Treitz. An opening was made in the jejunum, approximately 15 cm from the ligament of Treitz, to perform a side-to-side anastomosis between the proximal and distal jejunum. A circular stapler was used to perform a side-to-end anastomosis between the jejunum and lower esophagus. A linear stapler was then to transect and close the bowel at the window site. All the anastomoses were reinforced with interrupted silk sutures.

Group B: Uncut Roux-en-Y anastomosis. An appropriately sized stapler base was selected and placed at an opening in the jejunum, approximately 65 cm from the ligament of Treitz. The stapler was then inserted into the jejunum approximately 15 cm from the ligament of Treitz, and an opening was made proximally. A side-to-side anastomosis was performed in the jejunum approximately 8 cm from the ligament of Treitz. A circular stapler was then inserted proximally into the jejunum, and an end-to-side anastomosis was completed approximately 20 cm from the ligament of Treitz. All the anastomotic sites were reinforced with interrupted silk sutures.

Observation indicators and data collection

Statistical analyses were conducted on the baseline characteristics of the two groups of patients, including age, body mass index (BMI), sex, smoking and alcohol consumption status, tumor node metastasis (TNM) staging, lesion diameter, degree of tumor differentiation, and lymph node metastasis. Perioperative indicators, such as surgery duration, intraoperative blood loss, time to the first anal gas passage, and the average length of hospital stay, were also analyzed. Peripheral venous blood samples (3 mL) were collected preoperatively and three days postoperatively. The samples were centrifuged at 3000 rpm with a radius of 14 cm at room temperature for 10 minutes, and the upper serum layer was collected for further analysis. Indicators of gastrointestinal mucosal barrier function, including D-lactate, diamine oxidase (DAO), and endotoxin (ETX), were measured using enzyme-linked immunosorbent assay kits purchased from Shanghai Roche. Serum nutritional indicators such as serum albumin (ALB) and total protein (TP) were measured using an automatic biochemical analyzer (AU5800, Beckman Coulter), and the prognostic nutritional index (PNI) was calculated. Immunological indicators [cluster of differentiation (CD) 3 +, CD4 +, and CD8 +] were detected by flow cytometry using kits obtained from Shanghai Roche (Shanghai, China). The incidence of complications was recorded.

Statistical analysis

Data were analyzed using statistical product and service solutions 21.0. The levels of D-lactic acid, DAO and ETX measured in this study met the requirements for normal distribution and were described by mean ± SD. Comparisons between the two groups for these continuous variables were performed using a t-test. Categorical variables, such as gender, combined disease, TNM stage, were expressed as frequencies and percentages (%) to complete the statistical description, the statistical method between the groups using the χ² test; the statistical comparison criterion in the study was P < 0.05.

RESULTS

Analysis of the baseline characteristics’ balance between the two groups

The baseline characteristics of patients in group A and group B were analyzed to assess balance, and no significant differences were found (P > 0.05). See Table 1.

Table 1 Analysis of the baseline characteristics’ balance, mean ± SD/n (%).

General information	A group (n = 90)	B group (n = 82)	t/χ2	P value
Age (years)	65.9 ± 8.1	63.8 ± 7.6	1.749	0.082
BMI (kg/m2)	22.25 ± 2.20	22.45 ± 2.15	-0.602	0.548
Gender			0.268	0.604
Male	54 (60.00)	46 (56.1)
Female	36 (40.00)	36 (43.9)
Smoking			3.083	0.079
Yes	32 (35.56)	40 (48.78)
No	58 (64.44)	42 (51.22)
Tipple			1.995	0.158
Yes	28 (31.11)	34 (41.46)
No	62 (68.89)	48 (58.54)
TNM stage			2.892	0.089
I + II stage	61(67.78)	65 (79.27)
III stage	29 (32.22)	17 (20.73)
Focal diameter			2.2	0.138
≤ 3.0 cm	43 (47.78)	30 (36.59)
> 3.0 cm	47 (52.22)	52 (63.41)
Degree of tumor differentiation			2.393	0.122
High + medium differentiation	62 (68.89)	65 (79.27)
Poorly differentiated	28 (31.11)	17 (20.73)
Lymph node metastasis			3.123	0.077
Yes	38 (42.22)	24 (29.27)
No	52 (57.78)	58 (70.73)

BMI: Body mass index; TNM: Tumor node metastasis.

Comparison of surgical procedure indicators between the two groups of patients

The digestive tract reconstruction time for patients in group A was shorter than that for patients in group B (P < 0.05). However, there were no significant differences between group A and group B in terms of surgery duration, intraoperative blood loss, time to first anal gas passage, and average length of hospital stay (P > 0.05). See Table 2.

Table 2 Comparison of surgical procedure indicators between the two groups of patients, mean ± SD.

Group	n	Operation time (minutes)	Digestive tract reconstruction time (minutes)	Operative blood loss (mL)	Anal first exhaust time (hour)	Average length of stay (day)
A group	90	167.5 ± 14.3	24.8 ± 5.1	240.4 ± 48.1	46.9 ± 12.0	12.4 ± 2.4
B group	82	170.8 ± 17.2	27.0 ± 4.8	245.8 ± 43.7	45.1 ± 9.8	12.9 ± 2.8
t		-1.373	-2.906	-0.768	1.071	-1.261
P value		0.172	0.004	0.444	0.286	0.209

Comparison of gastrointestinal barrier function indicators between the two groups of patients

Preoperatively, the serum levels of D-lactate, DAO, and ETX were compared between group A and group B (P > 0.05). On the third day postoperatively, the serum levels of D-lactate, DAO, and ETX in both groups were significantly higher than their preoperative levels (P < 0.05). However, the serum levels of D-lactate, DAO, and ETX in group A were lower than those in group B on the third postoperative day (P < 0.05). See Table 3.

Table 3 Comparison of laboratory indicators related to gastrointestinal barrier function between the two groups, mean ± SD.

Group	n	D-lactic acid (mg/L)		DAO (IU/L)		ETX (EU/mL)
		Before operation	Postoperative 3 days	Before operation	Postoperative 3 days	Before operation	Postoperative 3 days
A group	90	2.43 ± 0.50	3.27 ± 0.61a	1.52 ± 0.40	2.11 ± 0.48a	0.41 ± 0.08	1.10 ± 0.21a
B group	82	2.30 ± 0.48	3.56 ± 0.67a	1.44 ± 0.45	2.24 ± 0.55a	0.43 ± 0.11	1.16 ± 0.24a
t		1.736	-2.971	1.234	-1.655	-1.372	-1.748
P value		0.084	0.003	0.219	0.100	0.172	0.082

^aP < 0.05.

P values compared with the preoperative group. DAO: Diamine oxidase; ETX: Endotoxin.

Comparison of nutritional indicators between the two groups of patients

Preoperatively, the PNI, serum ALB, TP, and body weight were compared between group A and group B (P > 0.05). One month postoperatively, the PNI, serum ALB, TP, and body weight in both groups were significantly lower than their preoperative levels (P < 0.05). However, the PNI and serum ALB levels in group A were higher than those in group B one month after surgery (P < 0.05). See Table 4.

Table 4 Comparison of nutritional indicators between the two groups of patients, mean ± SD.

Group	n	PNI		ALB (g/L)
		Before operation	One month after surgery	Before operation	One month after surgery
A group	90	55.91 ± 4.02	45.71 ± 4.00a	39.41 ± 3.44	35.10 ± 2.85a
B group	82	57.03 ± 5.18	43.31 ± 4.58a	40.42 ± 3.95	33.91 ± 3.02a
t		-1.592	3.668	-1.792	2.658
P value		0.113	0.000	0.075	0.009
Group	n	TP (g/L)		Body mass (kg)
		Before operation	One month after surgery	Before operation	One month after surgery
A group	90	70.33 ± 4.03	64.62 ± 3.96a	64.31 ± 5.30	61.80 ± 4.71a
B group	82	71.40 ± 4.55	63.70 ± 4.03a	65.88 ± 5.51	60.73 ± 4.48a
t		-1.635	1.509	-1.904	1.523
P value		0.104	0.133	0.059	0.130

^aP < 0.05.

P values compared with the preoperative group. PNI: Prognostic nutritional index; ALB: Albumin; TP: Total protein.

Comparison of immunological indicators between the two groups of patients

Preoperatively, the levels of CD3 +, CD4 +, and CD8 + were compared between the groups (P > 0.05). One month postoperatively, both groups showed a significant decrease in CD3 + and CD4 + levels and a significant increase in CD8 + levels compared to their preoperative levels (P < 0.05). However, the CD3 +, CD4 +, and CD8 + levels were compared between group A and group B one month after surgery (P > 0.05). See Table 5.

Table 5 Comparison of immunological indicators between the two groups of patients, mean ± SD.

Group	n	CD3 + (%)		CD4 + (%)		CD8 + (%)
		Before operation	One month after surgery	Before operation	One month after surgery	Before operation	One month after surgery
A group	90	63.20 ± 5.10	56.13 ± 4.77a	42.30 ± 4.46	38.37 ± 4.09a	24.42 ± 2.66	28.30 ± 2.96a
B group	82	64.51 ± 5.37	54.92 ± 4.40a	43.17 ± 4.85	37.45 ± 4.76a	25.07 ± 3.00	29.16 ± 3.05a
t		-1.641	1.724	-1.226	1.363	-1.506	-1.876
P value		0.103	0.087	0.222	0.175	0.134	0.062

^aP < 0.05.

P values compared with the preoperative group. CD: Cluster of differentiation.

Comparison of complication rates between the two groups of patients

The complication rate in group A was 10.00%, while in group B, it was 24.39%. The complication rate in group A was considerably lower than in group B (P < 0.05). See Table 6.

Table 6 Comparison of complication rates between the two groups of patients, n (%).

Group	n	Anastomotic fistula	Reflux esophagitis	Anastomotic ulcer	Diarrhea	Ileus	Complication rate
A group	90	2	2	0	4	1	9 (10.00)
B group	82	4	5	2	6	3	20 (24.39)
χ2							6.339
P value							0.012

DISCUSSION

Roux-en-Y anastomosis is a widely used method for digestive tract reconstruction after total gastrectomy. This surgical approach effectively preserves gastric function, is relatively straightforward to perform, and is associated with fewer postoperative complications, making it the preferred choice in clinical practice[10]. However, Roux-en-Y anastomosis remains somewhat controversial, particularly regarding the preservation of the duodenum, the construction of an appropriate reservoir, and whether to transect the jejunum. A study by Chen et al[11] demonstrated that using four linear-cutting staplers in total gastrectomy can reduce the complexity of the surgical procedure. In a study by Yang et al[12], the use of a double-channel interposed jejunal digestive tract reconstruction method has been shown to improve postoperative nutritional status and quality of life in patients with gastric cancer. Similarly, the findings of Li et al[13] indicated that regulatory double-channel digestive tract reconstruction is superior to Billroth I and non-duodenal bypass methods in improving patient survival outcomes and reducing postoperative complications. This study compared the effectiveness and safety of the modified and uncut Roux-en-Y methods for gastrointestinal anastomosis following total gastrectomy.

A comparison of the general data of patients who underwent different anastomosis techniques showed no significant differences between the two groups in terms of age, BMI, sex, tumor characteristics, and lymph node metastasis. This minimized the influence of these factors on surgical outcomes and postoperative complications, thereby ensuring a better balance between the two groups. The modified Roux-en-Y method demonstrated a significant advantage in terms of surgical duration and complexity. The modified Roux-en-Y anastomosis requires only the placement of the stapler base and, after creating an opening, allows for a straightforward side-to-side anastomosis between the proximal and distal jejunum[14]. In contrast, uncut Roux-en-Y anastomosis involves multiple openings and anastomoses at 65 cm, 15 cm, 8 cm, and 20 cm from the ligament of Treitz, making the procedure more complex and significantly increasing the surgery time[15].

Moreover, a comparison of gastrointestinal barrier function on the third postoperative day showed that the modified Roux-en-Y digestive tract reconstruction method can lower the damage to gastrointestinal mucosal function caused by surgery. Surgical trauma activates the immune system and triggers the release of large quantities of inflammatory mediators[16]. These inflammatory mediators disrupt the integrity of the intestinal mucosal barrier, thereby promoting the activity of DAO[17]. Additionally, inflammatory mediators activate proteases that degrade tight junction proteins in the intestinal mucosa, increasing its permeability[18]. When the intestinal mucosal barrier function is compromised, the gut microbiota and their metabolic products can enter the bloodstream, leading to elevated levels of bacterial metabolites such as D-lactate and ETX in the serum. Adequate postoperative intestinal blood flow supply is one of the key factors in maintaining intestinal barrier function. Insufficient blood flow supply can lead to intestinal ischemia and barrier dysfunction, which in turn can trigger the invasion of bacteria and their metabolites. Improving the Roux-en-Y digestive tract reconstruction method can not only reduce stress reactions in the gastrointestinal tract, but also improve postoperative intestinal microcirculation, maintain the nutritional supply of intestinal blood flow, enhance the repair ability of intestinal epithelial cells, and reduce barrier damage. Reduce D-lactate, DAO, and ETX levels, and improve the occurrence of gastrointestinal symptoms such as diarrhea in patients.

In addition to serving as a temporary storage organ for food, the stomach is also responsible for the initial digestion of nutrients, including proteins and certain minerals. After total gastrectomy, food enters the small intestine directly without undergoing gastric digestion, affecting the initial breakdown and absorption of nutrients. Changes in postoperative dietary habits and appetite, as well as the occurrence of complications such as diarrhea and gastrointestinal dysfunction, can affect the nutritional status of patients, resulting in varying degrees of reduction in the nutritional status of both groups of patients after surgery compared to before surgery. Nutritional status is closely related to postoperative wound healing, and insufficient nutrient intake can lead to slow wound healing. In this study, one month postoperatively, the PNI and serum ALB levels in group A were higher than those in group B, suggesting that the modified Roux-en-Y method for gastrointestinal anastomosis during total gastrectomy helps improve postoperative nutritional status. This may be because modified Roux-en-Y anastomosis reduces the systemic inflammatory response after surgery, thereby mitigating damage to the intestinal mucosal barrier, helping to restore the patient’s normal physiological functions and improve their postoperative quality of life.

T cells are crucial components of the immune system. CD3 + T cells represent the total population of T cells, CD4 + T cells are helper T cells, and CD8 + T cells are cytotoxic T cells[19]. Surgical trauma can activate stress responses in the body, leading to a reduction in immune function[20]. The results of this study showed no significant differences in immune levels between patients one month after surgery who underwent different digestive tract anastomosis methods, indicating that the two surgical approaches have a similar impact on short-term postoperative immune recovery. However, the recovery of immune function may be a relatively slow process, and there are differences in the dynamic changes of immune cell subsets at different time points after surgery. In the early postoperative period, the number of CD4 + cells may decrease due to immune suppression. As the wound heals and the immune system recovers, the number of CD4 + cells will gradually increase, but the speed and degree of recovery will be affected by nutrition and anastomosis methods. The dynamic changes of these cell subpopulations exhibit different trends, and the first and second weeks after surgery are critical periods for immune system recovery, with significant changes in the number and function of immune cells. If immune indicators are only observed one month after surgery, a more critical window of immune response may be missed. Therefore, further exploration is needed to determine whether different anastomosis methods have an impact on postoperative immune recovery. Additionally, the study found that the modified Roux-en-Y method for gastrointestinal anastomosis helped reduce the occurrence of surgical complications. This technique is relatively straightforward, reduces the number of anastomoses and procedural complexity, and thereby lowers the risk of complications such as anastomotic leakage, reflux esophagitis, anastomotic ulcers, diarrhea, and intestinal obstruction, demonstrating good clinical safety.

Future research can combine data on surgical risk, recovery speed, and postoperative complications to comprehensively evaluate the relationship between surgical time and patient prognosis, while extending the monitoring time of immune function to observe the long-term trend of immune system recovery.

CONCLUSION

In conclusion, using the modified Roux-en-Y method for gastrointestinal anastomosis during total gastrectomy is beneficial for shortening the gastrointestinal anastomosis time, reducing gastrointestinal mucosal damage caused by surgery, and minimizing the decline in postoperative nutritional levels. Overall, this approach helps reduce the occurrence of surgical complications.