Influence factors of clinical effects on patients with early gastric cancer: A retrospective study

Abstract

BACKGROUND

Identifying factors that influence non-curative resection (NCR) is critical to optimize treatment strategies and improve patient outcomes in patients with early gastric cancer (EGC).

AIM

To investigate the factors influencing the NCR of EGC and to evaluate the predictive value of these factors.

METHODS

The clinical data of 173 patients with EGC admitted between July 2020 and July 2023 were retrospectively collected. According to radical resection criteria, the patients were further divided into curative resection group (n = 143) and NCR group (n = 30). Clinical information was collected, including surgical method, tumor diameter, tumor site, ulcer formation, depth of invasion, pathological type, and lymph node metastasis. Logistic regression analysis was used to explore the factors affecting non-curable resection.

RESULTS

Multivariate logistic regression analysis showed that ulcer formation [odds ratio (OR) = 3.53; 95% confidence interval (CI): 1.55-8.01, P = 0.003], pathological type (OR = 3.73; 95%CI: 1.60-8.74, P = 0.002), tumor diameter (OR = 3.15; 95%CI: 1.40-7.05, P = 0.005), tumor location (OR = 3.50; 95%CI: 1.16-10.58, P = 0.027), lymph node metastasis (OR = 4.40; 95%CI: 1.83-10.57, P = 0.001), and depth of penetration (OR = 3.75; 95%CI: 1.60-8.74, P = 0.002) were all risk factors for NCR in EGC patients. Predictive analysis showed varying area under the curve values for factors such as tumor diameter (0.636), tumor location (0.608), ulcer formation (0.652), infiltration depth (0.658), pathological type (0.656), and lymph node metastasis (0.674).

CONCLUSION

The results suggest that factors such as tumor diameter, tumor location, ulcer formation, depth of invasion, pathological type, and lymph node metastasis increase the risk of NCR in EGC patients.

Key Words: Early gastric cancer; Non-curative resection; Endoscopic mucosal dissection; Influencing factors; Curative resection

Core Tip: In order to identify factors influencing non-curative resection (NCR) in patients with early gastric cancer (EGC) and assess the predictive value of these factors, a retrospective analysis was conducted on 173 EGC patients between July 2020 and July 2023. The cohort was stratified into two groups: Curative resection group (143 cases) and NCR group (30 cases) based on adherence to curative resection guidelines. Various risk factors were systematically documented and analyzed. The findings underscored that tumor diameter, location, ulceration, infiltration depth, pathological classification, and lymph node metastasis emerged as pivotal risk determinants for NCR in individuals with EGC.

INTRODUCTION

Gastric cancer (GC) is a common malignant tumor of the digestive tract. According to the 2020 global cancer survey data, the global incidence of new GC cases accounted for 5.6% of new cancer cases, ranking fifth in incidence rate, and the mortality rate of GC accounted for 7.7% of cancer deaths, ranking fourth in mortality rate[1]. In recent years, due to the accelerated pace of life and changes in dietary structure, the incidence of new GC cases in China accounts for 10.5%, and the number of deaths has reached 12.4%. The incidence of GC is increasing year by year and has a trend of becoming younger[2,3]. The clinical staging of GC is crucial for determining the prognosis and quality of life of patients. The five-year survival rate of early GC (EGC) is about 80%, which is much higher than that of advanced GC[4]. EGC refers to the tissue lesions confined to the mucosal layer or submucosal layer, regardless of the size of the lesion or whether it is accompanied by lymph node metastasis[5]. Clinically, surgical treatment is commonly used for EGC, and the five-year survival rate can reach over 90%. This procedure can effectively eradicate the diseased tissue, but it causes significant damage to the physiological anatomical structure of the gastrointestinal tract and is prone to various complications such as infection, which can affect the prognosis of patients[6]. With the development of endoscopic diagnosis and minimally invasive techniques, endoscopic submucosal dissection (ESD) has been widely used in the treatment of EGC patients due to its advantages of minimal trauma, fast recovery, fewer complications, and high quality of prognosis. It is a safe and economical first choice for feasible endoscopic treatment of EGC patients[7]. ESD is a new surgical technique based on mucosal resection, which expands the indications for GC surgery. This surgery can remove the lesion tissue as a whole and evaluate the curative effect of the resection based on the pathological results, which is an important criterion for judging the long-term prognosis of patients[8]. EGC is defined based on the depth of tumor invasion and lymph node metastasis. Theoretically, it holds a high potential for radical resection. Nevertheless, multiple factors can lead to non-curative resection (NCR)[9]. Researches have demonstrated that the pathological characteristics of patients, including the differences in tumor size, location, invasion depth, and histological type, can exert an impact on the resection efficacy[9,10]. The consequences of NCR in patients with EGC are serious, and residual tumor tissue may increase the risk of recurrence and metastasis, increasing the complexity of follow-up treatment[9]. The continuous progression of the tumor can induce symptoms such as pain, obstruction, and bleeding, thus interfering with patients’ daily life[11]. Furthermore, relevant studies have indicated that the long-term survival rate of patients who have undergone NCR is lower than that of those with curative resection, resulting in a shortened survival time[12]. Considering the risk associated with NCR for EGC, it is of profound clinical significance to explore the influencing factors of non-radical resection for EGC patients. In-depth analysis of these factors can provide scientific basis for improving the early radical treatment rate of GC and improving the prognosis of patients. Thus, it can better guide clinical treatment decision, reduce the adverse consequences of NCR, and improve the treatment effect and quality of life of EGC patients.

MATERIALS AND METHODS

General information

A retrospective analysis of the clinical data of 173 EGC patients admitted to our hospital from July 2020 to July 2023 was conducted. The inclusion and exclusion criteria of study population are as follows. Inclusion criteria: (1) EGC confirmed by computed tomography, endoscopic ultrasound (EUS), and pathological examination, and meeting the absolute indications or expanded indications for standardized endoscopic resection of EGC[13]; (2) EUS evaluation of tumor located in the mucosal layer or submucosal layer, lesion diameter ≤ 3 cm, and no coexisting ulcer; (3) Complete clinical data and surgery performed in our hospital; (4) No history of adjuvant chemotherapy before surgery; and (5) Conscious and being able to communicate and cooperate with treatment. Exclusion criteria: (1) GC with confirmed metastasis by computed tomography examination or postoperative pathological diagnosis; (2) Severe cardiovascular, pulmonary, hepatic, or renal dysfunction; (3) Coagulation dysfunction or undergoing anticoagulant or antiplatelet therapy; (4) Concurrent other malignant tumors or immune diseases; (5) High-risk anesthesia; and (6) Lymphatic or blood vessel invasion. Radical resection criteria: Patients with EGC were divided into curative resection group (143 cases) and NCR group (30 cases) according to radical resection criteria. In the curative resection group, the indicators were: Completely resected differentiated intramucosal carcinoma, ≤ 2 cm in size, negative vertical and horizontal margins, no ulceration, and no vascular invasion[14]. This study was approved by the Ethics Committee of Chonggang General Hospital in accordance with regulatory and ethical guidelines pertaining to retrospective research studies. Informed consent was waived for this retrospective study due to the exclusive use of de-identified patient data, which posed no potential harm or impact on patient care.

Surgical methods

Patients in both groups were disinfected and given tracheal intubation and general anesthesia before operation, and received conventional treatment after operation. During surgery, the resected lesion is measured and fixed for pathological examination, and additional surgery is required if cancer cells remain. During the operation, the patient was lying on the left side. The lesion location was evaluated by endoscopy and marked with electric coagulation, and then a mixture of glycerin, indocyanine green, epinephrine, fructose, and sodium chloride were injected. After the lesion rose, the submucosa of the lesion was cut along the mark and separated by an insulated-tipped knife. After accurate assessment of the tumor condition before surgery, a 3 cm incision was made in the midline of the abdomen to observe tumor invasion and lymph node metastasis. A distal resection was executed, with the resection line positioned 5 cm proximal to the tumor and extending 4 cm distal to the pyloric sphincter. This procedure was followed by a D1 lymph node dissection, digestive tract reconstruction, subtotal gastrectomy, intestinal tube and residual stomach suture, and ultimately, hemostasis and meticulous layer-by-layer closure of the abdominal cavity.

Clinical efficacy

In this study, patients were divided into ESD group (87 cases) and surgical group (86 cases). According to the mode of surgery, the clinical efficacy of EGC patients in both groups was evaluated, including curative resection and en bloc resection[15,16]. Curative resection: En bloc resection, negative horizontal and vertical margins of the lesion, no infiltration of cancer cells in the margin and base, and no risk of lymph node metastasis. The endoscopic curability (eCura) A: (1) No ulcer, mainly differentiated intramucosal cancer; (2) No ulcer, lesion diameter ≤ 2 cm, mainly undifferentiated intramucosal cancer; and (3) Ulcer, diameter ≤ 3 cm, mainly differentiated intramucosal cancer. The eCura B: Diameter ≤ 3 cm, mainly differentiated superficial submucosal cancer. The eCuraC: It does not fulfill the criteria for either eCura A or eCura B, classifying it instead as eCuraC, which signifies NCR. En bloc resection: The tumor, along with the surrounding tissue and regional lymph nodes, is completely removed and obtained as a single specimen.

Data collection

All demographic data and medical history ware obtained from the medical history system. Clinical indicators of EGC patients were retrospectively collected, including tumor diameter, tumor location, ulcer formation, depth of invasion, pathological type, and lymph node metastasis. The assignment information of clinical indicators is shown in Table 1.

Table 1 Assignment table of independent variables.

Variable variables	Assignment
Diameter of tumor	0: Tumor diameter < 20 mm; 1: Tumor diameter ≥ 20 mm
Tumor location	0: Lower stomach; 1: Upper middle stomach
Ulcer formation	0: No; 1: Yes
Depth of penetration	0: Mucosal; 1: Submucosa
Pathological type	0: Differentiated type; 1: Undifferentiated type
Lymph node metastasis	0: No; 1: Yes

Statistical analysis

Statistical analysis was performed using SPSS version 27.0 software (Inclusion body myositis corps, Armonk, NY, United States). For continuous variables, normality tests were conducted, if the data follow normal distribution, continuous variables are presented as mean ± SD and compared using Student’s t-test, while non-normally distributed variables are presented as median (interquartile range) and compared using Mann-Whitney U test. Categorical variables are expressed as numbers and percentages, and χ² test was used for comparison between groups. Multivariate logistic regression was used to explore risk factors for NCR in patients with EGC; receiver operating characteristic was analyzed and area under curve (AUC) was calculated. The optimal cut-off value of the predictor was calculated using the Youden index method. Two-sided P < 0.05 was considered as statistical significance.

RESULTS

Clinical characteristics of EGC patients

According to the criteria of curative resection, 173 EGC patients were divided into the curative resection group (143 cases) and the NCR group (30 cases). There was no significant difference between the two groups in terms of gender, age, family history of GC, Helicobacter pylori infection history, combined depressed lesion, and combined mucosal lesion (P > 0.05). There were significant differences in tumor diameter, tumor location, ulcer formation, depth of penetration, pathological type, and lymph node metastasis (P < 0.05) (Table 2).

Table 2 Clinical characteristics of early gastric cancer patients.

Characteristics		Number of patients	CRG (n = 143)	NCRG (n = 30)	χ2	P value
Gender	Male	126	108	18	3.020	0.082
	Female	47	35	12
Age (years)	≥ 65	66	53	13	0.413	0.520
	< 65	107	90	17
Family history of stomach cancer	Yes	41	36	5	0.993	0.319
	No	132	107	25
Tumor diameter (mm)	≥ 20	59	42	17	8.221	0.004
	< 20	114	101	13
Tumor location	Upper and middle part of stomach	119	93	26	5.404	0.020
	Lower part of stomach	54	50	4
Ulcer formation	Yes	66	47	19	9.755	0.002
	No	107	96	11
Depth of infiltration	Mucous membrane layer	97	88	9	10.014	0.002
	Submucosa	76	55	21
History of Helicobacter pylori infection	Yes	44	36	8	0.029	0.865
	No	129	107	22
Pathological type	Differentiation type	85	78	7	9.666	0.002
	Undifferentiated type	88	65	23
Consolidation of depressed lesions	Yes	106	91	15	1.943	0.163
	No	67	52	15
Consolidation of mucosal lesions	Yes	118	98	20	0.040	0.842
	No	55	45	10
Lymph node metastasis	Yes	77	55	22	12.209	0.001
	No	96	88	8

CRG: Curative resection group; NCRG: Non-curative resection group.

Comparison of clinical efficacy of surgery methods in EGC patients

In this study, EGC patients were divided into ESD group (87 cases) and the surgical group (86 cases) according to the type of surgery they received. There was no significant difference between the ESD group and surgical group in term of the curative resection rate (P = 0.442) and en bloc resection rate (P = 0.072) (Table 3). The results indicated that the surgery method is not the factors that influence the curation for EGC patients.

Table 3 Comparison of clinical efficacy in the study population.

Group	Curative resection rate (%)	En bloc resection rate (%)
ESD group (n = 87)	80.46	94.25
Surgical group (n = 86)	84.88	100
χ2	0.591	3.248
P value	0.442	0.072

ESD: Endoscopic submucosal dissection.

Multivariate logistic regression

Multivariate logistic regression analysis showed that ulcer formation [odds ratio (OR) = 3.53; 95% confidence interval (CI): 1.55-8.01, P = 0.003], pathological type (OR = 3.73; 95%CI: 1.60-8.74, P = 0.002), tumor diameter (OR = 3.15; 95%CI: 1.40-7.05, P = 0.005), tumor location (OR = 3.50; 95%CI: 1.16-10.58, P = 0.027), lymph node metastasis (OR = 4.40; 95%CI: 1.83-10.57, P = 0.001), and depth of penetration (OR = 3.75; 95%CI: 1.60-8.74, P = 0.002) were all risk factors for NCR in EGC patients (Table 4).

Table 4 Multivariate logistic regression analysis of factors affecting non-curative resection in early gastric cancer patients.

Factors	Regression coefficient	Standard error	Z value	Wald χ2	P value	OR value	95%CI
Diameter of tumor	1.146	0.412	2.783	7.746	0.005	3.15	1.40-7.05
Tumor location	1.251	0.565	2.215	4.904	0.027	3.50	1.16-10.58
Ulcer formation	1.261	0.419	3.012	9.071	0.003	3.53	1.55-8.01
Depth of penetration	1.317	0.434	3.036	9.217	0.002	3.73	1.60-8.74
Pathological type	1.317	0.434	3.036	9.217	0.002	3.73	1.60-8.74
Lymph node metastasis	1.482	0.447	3.313	10.976	0.001	4.40	1.83-10.57

OR: Odds ratio; CI: Confidence interval.

Receiver operating characteristic curve for NCR in EGC patient

As shown in Figure 1 and Table 5, the AUC value of tumor diameter was 0.636, with a sensitivity of 0.567 and specificity of 0.706; the AUC value of tumor location was 0.608, with a sensitivity of 0.867 and specificity of 0.35; the AUC value of ulcer formation was 0.652, with a sensitivity of 0.633 and specificity of 0.671; the AUC value of depth of penetration was 0.658, with a sensitivity of 0.7 and specificity of 0.615; the AUC value of pathological type was 0.656, with a sensitivity of 0.767 and specificity of 0.545; the AUC value of lymph node metastasis was 0.674, with a sensitivity of 0.733 and specificity of 0.615.

Figure 1 Predictive value of each factor for non-curative resection in early gastric cancer patients. AUC: Area under the curve.

Table 5 Predictive value of each factor for non-curative resection in early gastric cancer patients.

Characteristic	AUC value	Sensitivity	Specificity
Diameter of tumor	0.636	0.567	0.706
Tumor location	0.608	0.867	0.35
Ulcer formation	0.652	0.633	0.671
Depth of infiltration	0.658	0.7	0.615
Pathological type	0.656	0.767	0.545
Lymph node metastasis	0.674	0.733	0.615

AUC: Area under the curve.

DISCUSSION

A total of 173 patients with EGC requiring surgical treatment were included in this retrospective study. The results suggest that factors including tumor diameter, tumor location, ulcer formation, depth of invasion, pathological type, and lymph node metastasis may increase the risk of NCR in EGC patients. We found that larger tumor diameter may be a risk factor for NCR in EGC patients. Kim and Lee[17] found that tumor diameter is closely related to NCR. Tumor size is a key indicator for evaluating the efficacy of EGC treatment. Tumors with a diameter ≥ 20 mm are more difficult to remove, and as the tumor grows, its diameter increases, exceeding the scope of endoscopic surgery, making it more difficult to achieve complete surgical resection and increasing the risk of recurrence. Therefore, for EGC patients with a tumor diameter ≥ 20 mm, comprehensive preoperative assessment should be strengthened to reduce the deviation in tumor size evaluation, develop targeted treatment plans to ensure the cleanliness and integrity of the lesion tissue, and increase postoperative monitoring and follow-up to timely detect and treat recurrence. This study also found a significant correlation between tumor location and EGC treatment effect. Park et al[18] found that lesions located in the upper part of the stomach increase the risk of NCR in EGC patients. High gastric body tumors located below the cardia and on the greater curvature side have special lesion positions that are more susceptible to limitations in endoscopic inversion operation and surgical field of view, leading to increased difficulty in preoperative lesion observation and surgical operation. Kim and Lee[17] found that lesions located in the upper part of the stomach require inversion of the endoscope within the gastric body, which increases the difficulty of endoscopic biopsy and carries a higher risk of missed diagnosis and missed detection due to the larger gastric cavity space in this area. Therefore, for EGC patients with high gastric body tumors, detailed observation of the lesion location and surrounding tissues should be conducted during preoperative evaluation, appropriate surgical methods should be selected, and experienced surgeons should be arranged to perform the surgery to ensure the integrity of tumor removal. This study also found that ulcer formation may be a risk factor for non-curable excision in patients with EGC. Ma et al[19] found that lesions with ulcers are the primary risk factor for NCR in EGC patients. Ulcerative scars or active ulcers can cause adhesion of gastric mucosal tissue during surgery, resulting in fragmentary resection and positive margins. Insufficient elevation of the lesion after submucosal injection and involvement of the mucosal muscle layer are common in these cases. Therefore, for EGC patients with ulcers, multiple biopsies should be avoided before surgery to reduce the risk of secondary tissue proliferation and adhesion. A study by Park et al[20] suggested that accurate assessment of the depth of invasion is crucial for determining the curative resection of endoscopic surgery. The mucosal sublayer of the gastric body and the bottom is relatively thin, and the capillary lymphatic vessels above the mucosal muscle are abundant. Deep infiltration carries a higher risk, increasing the difficulty and risk of dissection. Therefore, for EGC patients with infiltration into the submucosal layer, comprehensive preoperative evaluation should be strengthened, and imaging-enhanced techniques and staining endoscopy should be used to determine the depth of invasion of the lesion, combined with EUS to improve the detection rate of invasive integration. Yang et al[21] found that undifferentiated EGC increases the probability of NCR after surgery. Undifferentiated EGC has a greater difference in cell morphology compared to normal gastric mucosal tissue, making it difficult to determine the true origin of the tissue. It grows rapidly, has a high degree of malignancy, and is prone to local invasion and distant metastasis, severely affecting patient prognosis. Therefore, for patients with undifferentiated EGC, comprehensive preoperative evaluation should be completed as early and as thoroughly as possible, and a comprehensive treatment plan should be formulated based on multiple risk factors for NCR. Surgical resection may be added if necessary, and postoperative follow-up should be increased to detect and treat recurrence in a timely manner. Lymphatic vessel invasion is the primary risk factor for lymph node metastasis in EGC[22]. EGC patients with lymph node metastasis are more likely to have NCR after surgery and require additional surgical treatment. The lymphatic vessel network is located in the mucosal muscle layer and below, and deep infiltration of lymphatic vessels significantly increases the risk of lymph node metastasis. Factors such as lesions with ulcers and positive vertical margins can also lead to secondary lymph node metastasis. Therefore, for EGC patients with lymph node metastasis, multiple techniques and endoscopic examinations should be used to increase the detection rate of lymph node metastasis, and additional laparoscopic gastric resection and lymph node dissection should be performed to effectively remove lymph nodes and related lesions and reduce the risk of recurrence. There are still some limitations in this study: Firstly, this study is a single-center retrospective study with limited sample size. Secondly, due to the limitation of retrospective collection of medical record system information, the baseline information collected from EGC patients was limited, and the impact of confounding factors on the results of this study could not be considered. Therefore, it is necessary to further expand the sample size and conduct multi-center studies in the future to validate the results of this study and further explore more possible risk factors for non-curable resection in EGC patients.

CONCLUSION

In summary, both ESD and surgical treatment have good clinical effects in treating EGC patients. Tumor diameter, tumor location, ulcer formation, depth of invasion, pathological type, and lymph node metastasis can increase the risk of NCR in EGC patients. It is necessary to strictly control the indications for EGC surgery, conduct comprehensive preoperative assessments, establish a risk assessment system, and develop accurate treatment plans to improve patient prognosis.

ACKNOWLEDGEMENTS

The authors express their appreciation to the staffs in the Chonggang General Hospital for their technical assistance.