Early gastric cancer (EGC) usually has no symptoms, and when symptoms appear, it often indicates advanced cancer, so gastric cancer remains an important threat to global health. Early diagnosis of gastric cancer is critical to improving survival rates, and gastric cancer screening using endoscopy has become an important method. Endoscopic screening can detect carcinoma in situ and precancerous lesions as early as possible. Once EFB pathology is diagnosed as carcinoma in situ, low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), gastroenterologists usually recommend endoscopic submucosal dissection (ESD) to completely remove the diseased tissue and prevent further cancer. However, EFB is not representative of the entire lesion because only a small percentage of lesions are sampled. The LU et al. [1] study showed that the consistency rate between preoperative biopsy and postoperative pathological specimens was 68.92%. The RYU et al. [2] study showed that the difference rate between preoperative pathological biopsy and postoperative pathological diagnosis of ESD was 31.1%, so EFB technology may underestimate the extent of gastric mucosal lesions. Although ESD is less invasive than surgery, there are still some potential complications, including bleeding or perforation, so it is necessary to evaluate the pathological diagnosis of EFB prior to ESD. In this study, the pathological escalation rate of gastric mucosal lesions after ESD in 5 hospitals in northern Shaanxi was counted, and the relevant factors of pathological escalation were analyzed, so as to determine which characteristic lesions may appear pathological upgrade, hoping to provide some guidance for clinical practice.
1 Information and methodology
1.1 Study Subjects Patients who underwent ESD treatment due to gastric mucosal lesions in the Affiliated Hospital of Yan'an University, Yan'an People's Hospital, Yulin First Hospital, Yan'an Hospital of Traditional Chinese Medicine and Zichang People's Hospital from 2016 to 2021 were collected as study subjects who met the enrollment criteria. Inclusion criteria: (1) meet the indications for gastric ESD and the indications for expansion; (2) Sign informed consent before ESD surgery; (3) EFB before ESD surgery. Exclusion criteria: (1) imperfect clinical pathological records; (2) The pathological diagnosis was mild inflammation, ultrasound gastroscopy was highly suspected of gastrointestinal stromal tumor, ectopic pancreas, neuroendocrine tumor, and ESD was finally diagnosed as stromal tumor, ectopic pancreas and neuroendocrine tumor.
1.2 Pathological classification Pathological classification refers to the mainland gastric cancer diagnosis and treatment standard guidelines[3]: LGIN refers to mild, mild-moderate and moderate dysplasia; HGIN refers to moderate-severe, moderate dysplasia and carcinoma in situ; EGC means that the depth of invasion of cancer tissue does not exceed the submucosa, regardless of lymph node metastasis; Advanced gastric cancer refers to the invasion of cancer tissue deeper than the submucosa to reach the muscular layer of the stomach wall or deeper. This study divided the pathological types into 5 categories: chronic inflammatory changes (CICs), including hyperplastic polyps, adenomatous polyps; LGIN, HGIN, EGC and advanced gastric cancer.
1.3 Grouping method The subjects were classified according to the differences in preoperative biopsy diagnosis and postoperative pathological diagnosis, and the postoperative pathological diagnosis was classified as upgraded and the non-upgraded were classified as unupgraded, and the patients diagnosed with CIC, LGIN and HGIN before EFB were compared respectively, and the relevant factors of pathological escalation were analyzed.
1.4 Statistical Methods Use SPSS 26.0 statistical software to perform statistical analysis and processing of data. The counting data were expressed as relative numbers, and the χ2 test was used for comparison between groups. Multivariate logistic regression analysis was used to explore the influencing factors of pathological progression. The difference in P<0.05 was statistically significant.
2 Results
2.1 General characteristics A total of 241 cases were included in this study, including 148 males (61.4%) and 93 females (38.6%); Age 27~82 years old, average age (60.6±9.8) years, > 130 cases (53.9%) aged 60; 65 cases (26.9%) were positive for Helicobacter pylori (Hp); Thirty-one (12.9%) lesions were located in the cardia, 5 (2.1%) in the fundus, 54 (22.4%) in the stomach body, 28 (11.6%) in the gastric horn, and 123 (51.0%) in the antrum.
2.2 Comparison of preoperative EFB and postoperative pathological results of ESD The overall upgrade rate of preoperative EFB diagnosis and postoperative pathological diagnosis of ESD was 31.5% (76/241) (Table 1).
2.3 Analysis of factors related to pathological escalation after ESD surgery
2.3.1 Univariate Analysis of Pathological Escalation The preoperative EFB diagnosis of different endoscopic types and surface ulcers was a statistically significant difference in the rate of postoperative pathological escalation in CIC patients (P<0.05). There were significant differences in the postoperative pathological escalation rate of patients diagnosed with LGIN at different ages, different endoscopic classifications, whether the surface was red, whether the surface was ulcerated, and the number of materials taken from different preoperative EFB (P<0.05). The postoperative pathological escalation rate of patients with preoperative EFB diagnosis of HGIN with different lesion sizes was statistically significant (P<0.05), as shown in Table 2.
2.3.2 Multivariate analysis of pathological escalation Whether the postoperative pathology of patients diagnosed with preoperative EFB as CIC, LGIN, and HGIN was upgraded to the dependent variable (assignment: yes=1, no=0), and the statistically significant variables in univariate analysis were used for multivariate logistic regression analysis [assignment: endoscopic typing (raised type = 1, flat type = 2, depressed type = 3), surface ulcer (with = 1, no = 2), age (> 60 years old = 1, ≤ 60 years old = 2), surface redness (with = 1, none = 2), surface ulcer (with = 1, none = 2), number of materials taken (1 piece = 1, ≥ 2 pieces = 2), lesion size (> 2 cm = 1, ≤ 2 cm = 2)), the results showed that endoscopic classification and surface ulcer were the influencing factors of postoperative pathological escalation of ESD in patients with preoperative EFB diagnosis of CIC (P<0.05). Age, endoscopic classification, surface redness and number of materials taken were the influencing factors of postoperative pathological escalation of ESD in patients diagnosed with LGIN with preoperative EFB (P<0.05). Lesion size was an influencing factor (P<0.05) for postoperative pathological escalation of ESD in patients with preoperative EFB diagnosis of HGIN, as shown in Table 3.
3 Discussion
In this study, a retrospective study of 241 patients in 5 hospitals in northern Shaanxi found that the overall upgrade rate of pathological diagnosis after EFB and ESD was 31.5%, and if the cases diagnosed with EGC were excluded, the pathological escalation rate was 33.9%, which was at the median level of similar studies at home and abroad.
In this study, among the 84 patients diagnosed with CIC by EFB, 27 cases eventually developed pathological escalation, of which 5 cases were upgraded to EGC, with an escalation rate of 32.1%, and further univariate analysis showed that pathological escalation was related to endoscopic classification and surface ulceration, and were independent factors of pathological escalation. The pathological escalation rate of CIC in this study was slightly lower than that of foreign BAEK et al. [4], which obtained a pathological escalation rate of 43.1% after gastritis or hyperplastic lesions ESD, but overall, for CIC lesions, the pathological escalation rate in this study was higher, and the reasons may be related to the following: (1) The CIC lesions that were finally treated with ESD were lesions that endoscopists considered to have carcinogenesis potential, which were lesions after secondary selection, and could not yet represent the pathological escalation of all CIC lesions; (2) The lesion may be a mixed lesion of inflammation, hyperplasia and neoplasia, EFB can only represent the pathology of the biopsy site, not the entire lesion, the lesion may be limited. It suggests that the diagnosis of EFB as CIC (including inflammation, polyps, etc.) does not completely exclude the possibility of EGC or precancerous lesions, and should be paid attention to in cases of flat or depressed endoscopic and superficial ulcers, and gastroscopy and biopsy can be performed again if necessary.
Intraepithelial neoplasia is a precancerous lesion with a clear carcinogenic potential, which is divided into LGIN and HGIN. HGIN currently recommends endoscopic submucosal resection (EMR) or ESD; For LGIN, the mainland recommends follow-up or surgical treatment [5], follow-up for those without factors related to pathological escalation, and ESD treatment for those with factors related to pathological progression. However, there are no clear criteria for factors related to pathological escalation. In LIM et al. [6], the consistency rate of pathological diagnosis before and after ESD of intraepithelial neoplasia was 31.7% (587/1 850), of which the pathological escalation rate of LGIN was 24.0%, the pathological escalation rate of HGIN was 52.7%, and the relevant factor of pathological progression of LGIN was the maximum diameter of the lesion > 1.8 cm (P=0.001), uneven surface (P=0.014) and concave type (P=0.001) under endoscopic classification; A comparative study of the accuracy of preoperative and postoperative pathological diagnosis of ESD in HGIN [7] showed that the pathological diagnosis escalation rate was 66.5%, and surface ulcers (OR=4.151), superficial nodules (OR=5.582), surface redness (OR=2.926), and lesions located on the stomach 1/3 (OR=3.894) were the relevant factors for pathological escalation. Wu Shimin [8] showed that the postoperative pathological escalation rate of ESD in lesions diagnosed with LGIN was 29.5%, and surface redness and surface ulceration were associated with postoperative pathological escalation of ESD (P<0.05). Li Zhigui et al. [9] showed that the small number of biopsies, the diameter of lesions > 1 cm, the raised lesions, and the ulcer type were the relevant factors of EGC missing the diagnosis of HGIN. The study of Yifan Chen [10] suggested that the postoperative pathological escalation rate of ESD was 50.4% for lesions diagnosed with HGIN before EFB, and the lesion diameter was > 3 cm (OR=0.261) and male (OR=3.371) as the relevant factors for pathological progression.
In this study, 32.0% of the lesions diagnosed with LGIN by EFB underwent ESD surgery, and the gender, age, lesion location, lesion size, endoscopic classification, surface redness, surface nodules, surface ulcers, Hp, and number of materials were analyzed, and finally it was found that the pathological escalation was related to age > 60 years, endoscopic classification as flat, surface redness, surface ulcers and the number of materials, and further multivariate analysis found that the age was > At 60 years old, the endoscopic classification was flat, the surface redness, and the number of materials taken were independent related factors of LGIN pathological progression. Preoperative EFB was diagnosed as HGIN, and pathological escalation occurred in 38.5% of cases after ESD surgery, and lesion size was an independent factor related to pathological escalation. The results of this study showed that the overall pathological upgrade rate of 31.5% was at the middle level of relevant research results at home and abroad, and the relevant factors of pathological progression were similar to other research results. Therefore, for lesions with LGIN biopsy before surgery, attention should be paid to patients > 60 years old, flat endoscopic type, and surface redness, and ESD resection can be performed if necessary; For lesions diagnosed with EGIN by EFB, if the lesion size is > 2 cm, the possibility of carcinogenesis should be alerted.
EFB and ESD postoperative pathological results are not completely consistent, domestic and foreign studies have reported, combined with the actual clinical work, pathological escalation may have the following reasons, (1) endoscopy and pathologists reasons: all the results of this study are obtained in cases, some cases in county-level hospitals for preoperative biopsy, postoperative specimens after ESD in higher-level hospitals for pathological diagnosis, county-level hospital endoscopists and pathologists may lack experience in diagnosis, HOSOKAWA ET AL. [11] FOUND THAT THE MISSED DIAGNOSIS RATE OF EGC AMONG ENDOSCOPISTS WITH 10 YEARS OF WORK EXPERIENCE WAS ONLY 19.5%, WHILE IT WAS 32.40% FOR LESS THAN 10 YEARS, AND LI ZHIGUI ET AL. [9] RESEARCH ALSO CONFIRMED THIS RESULT; (2) Cause of lesion: the lesion may be a punctate lesion, and there may be uneven distribution of lesions, while EFB can only clamp a small piece of lesion, which cannot fully represent the entire lesion; (3) Reasons for biopsy specimens: When biopsy is carried out in this study, the lesions of general clamping are small, and usually can only clamp to the mucosal layer and propria of the lesion, and rarely reach the muscular layer of the mucosa, however, JEON et al. [12] research suggests that large forceps biopsy can not increase the accuracy of biopsy, and can only be achieved by increasing the number of biopsies. In clinical work, there may be an insufficient number of biopsies, and it has been reported that if seven endoscopic biopsy samples are available, the diagnosis rate of advanced gastric cancer is > 98% [13], but for superficial gastric tumors, especially small lesions, multiple endoscopic biopsies may be an obstacle to endoscopic resection because submucosal fibrosis is induced by endoscopic biopsy [14], and submucosal fibrosis is a major risk factor for perforation after ESD surgery. Based on this, the "China Early Gastric Cancer Screening and Endoscopic Diagnosis and Treatment Consensus Opinion (April 2014, Changsha)" [3] proposed that if the diameter of the lesion is > 1 cm, at least 2 specimens are taken, and for every 1 cm increase in the diameter of the lesion, 1 specimen is added, when the lesion tends to advanced cancer, the necrotic area should be avoided and 6~8 specimens should be collected, the specimen should be as large as possible, the depth should reach the muscular mucosa, in the actual clinical work, due to the presence of surface ulcers in the lesion or the difficulty of biopsy at the location of the lesion, etc. There may be cases where the number or depth of biopsies is insufficient. (4) Reasons for differences in diagnostic criteria: It has been reported that Japanese and Western pathologists diagnosed 35 gastric biopsy and excision specimens with suspicious early tumor lesions, and Western pathologists only diagnosed suspected or confirmed cancer in less than 50% of the specimens, but Japanese gastrointestinal pathologists diagnosed suspected or confirmed cancer in more than 80% of the specimens [15]. Therefore, endoscopists and pathologists should actively improve the level of operation and diagnosis, pay enough attention to cases of surface redness, surface ulcers, and flat lesions, and take biopsies in strict accordance with the guidelines, the number and depth should meet the requirements, and actively communicate with pathologists to avoid missing diagnoses, and use magnification and staining endoscopes for some key pathologies to better observe the lesions and improve the representativeness of biopsies.
There are still some shortcomings in this study, first, this study is retrospective, there is inherent selectivity bias, and the data are relatively limited; Secondly, there were no magnification, staining endoscopic and ultrasound endoscopic results in the included data, and the conclusions reached had certain limitations. In the future, the authors will expand the research center, increase the number of cases, and include magnification, staining and endoscopic ultrasound results in the study to improve the representativeness of the data.
There is no conflict of interest in this article.
Bibliography
Source: GAO Rongjian, WU Haili, BI Xinhong, et al. Analysis of factors related to pathological escalation after endoscopic submucosal dissection of gastric mucosal lesions[J]. China General Practice,2023,26(26):3325-3329. DOI：10.12114/j.issn.1007-9572.2023.0012.