- Open Access
Chinese integrated guideline on the management of gastric precancerous conditions and lesions
Chinese Medicine volume 17, Article number: 138 (2022)
The standardized diagnosis and management of gastric precancerous conditions and lesions are important to prevent gastric cancer. This guideline, created by 5 traditional Chinese medicine and Western medicine associations, based on the current morbidity and diagnosis and treatment of gastric precancerous conditions and lesions, provides specific key points and strategies for diagnosis and treatment in the following five aspects: definition and epidemiology, diagnosis and stage, surveillance, treatment and efficacy evaluation. It is hoped that these aspects, assessed by integrating Western medicine and traditional Chinese medicine and involving multidisciplinary participation, will play a guiding role in clinical diagnosis and treatment and achieve effective secondary prevention of gastric cancer.
China has a high incidence of gastric cancer [1, 2], with approximately 679,000 new cases of gastric cancer and 498,000 deaths occurring every year. The morbidity and mortality of gastric cancer increase with age , posing a serious threat to people's health and causing a huge medical burden. Early detection and treatment of precancerous lesions of gastric cancer, including precancerous diseases (precancerous conditions) and precancerous lesions of gastric cancer (PLGC), is an effective measure to prevent the development of gastric cancer.
The Correa model of gastric adenocarcinoma is generally recognized by the academic community . Much work has been done, and certain achievements and consensus have been achieved in the fields of traditional Chinese medicine and Western medicine on the diagnosis and treatment of Helicobacter pylori (H. pylori), gastric cancer risk stratification based on atrophy of the gastric mucosa and IM, and treatment and evaluation of PLGC. It is necessary to organize the knowledge about precancerous lesions of gastric cancer and make reasonable primary and secondary prevention programs. The successful publishing of the Management of epithelial precancerous conditions and lesions in the stomach (MAPS II)  guidelines,updated in 2019, and the Chinese consensus on the management of gastric epithelial precancerous conditions and lesions (2020)  reflect the great importance of the standardized diagnosis and treatment of gastric precancerous lesions in the field of gastroenterology. Previously, relevant contents were reported in the Chinese Consensus on Chronic Gastritis (2017) , Expert Consensus on the standardized diagnosis and treatment of gastric low-grade intraepithelial neoplasia (2019) , Consensus on the clinical application of gastric mucosal targeted biopsy technology (2018) ,and Consensus opinions of Traditional Chinese Medicine (TCM) experts in the diagnosis and treatment of chronic gastritis (2017) . This guideline was established by organizing and integrating the data on precancerous lesions in the fields of traditional Chinese medicine and Western medicine from the Digestive Tumor Cooperative Group of Spleen and Stomach Diseases Branch of the China Association of Traditional Chinese Medicine and the Gastroenterology Branch of Chinese Medical Association as the co-lead agency and provided as a reference for clinical practice.
The literature search and evaluation were carried out according to the topics determined by the guideline working group based on discussion. The exposure draft was written based on the extracted data after compositing, discussing and modifying the data. The quality of clinical evidence was assessed as high, middle and low using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The recommendation level was determined through discussion by experts. Then, the preliminary draft was revised many times according to the responses and opinions obtained from two rounds of Delphi expert consultation. The final expert consensus meeting was held on June 5, 2020. These guidelines were established by the votes of 58 gastroenterologists from all over the country, which were based on the full discussion of each statement reported by the experts in the writing group. The statement for which agreement was obtained from all or more than 80% of the members could be adopted; otherwise, a second discussion and vote was conducted by all members, and a third vote decided whether the statement for which the above-mentioned standard was accepted or rejected. This guideline included a total of 48 recommendations involved in five sections: definition and epidemiology, diagnosis and stage, monitoring, treatment, and efficacy evaluation (Table 1).
Definition and epidemiology
The development of gastric cancer is a multifactor and multistep process. The generally accepted Correa evolution model of intestinal gastric cancer is that gastric mucosa exhibits inflammation and atrophy, intestinal metaplasia (IM), and dysplasia (intraepithelial neoplasia) in steps under the influence of H. pylori infection and other factors and finally develops into gastric adenocarcinoma.
In 1972, the World Health Organization (WHO) classified precursors of gastric cancer into precancerous diseases and precancerous lesions and proposed the concept of precancerous lesions . Gastric precancerous diseases include gastric ulcers, chronic atrophic gastritis (CAG), gastric polyps, remnant stomach, Ménétrier's disease and so on.
Gastric precancerous lesions refer to pathological changes that are easily transformed into cancerous tissues, and dysplasia is a direct precancerous lesion. Some Western scholars also classify atrophy, IM and dysplasia as broad precancerous lesions.
In 1978, the WHO approved the unified use of the term dysplasia  and defined its degree, which was divided into mild, moderate and severe grades.
In 2000, the WHO International Agency for Research on Cancer  recommended the use of the term gastric epithelial neoplasia (GIN).
In 2010, the WHO recommended that the terms dysplasia and intraepithelial neoplasia should be used equally . Dysplasia focuses on morphological changes, while intraepithelial neoplasia emphasizes the process of tumor evolution, which can be divided into low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia (HGIN).
The updated 2019 WHO classification  suggested that the term gastrointestinal dysplasia be adopted, which can be divided into low-grade dysplasia (LGD) and high-grade dysplasia (HGD).
This guide is focused on gastric mucosal dysplasia and its background lesions, namely, CAG and IM.
Statement 1. The prevalence rate of chronic atrophic gastritis in China is relatively high and increases with age
The prevalence of CAG varies greatly in different countries and regions and is related to the H. pylori infection rate, environmental factors, genetic background, diagnostic methods, etc. The prevalence of CAG is positively correlated with the incidence of gastric cancer.
The prevalence of CAG in China is relatively high. In 2014, a cross-sectional survey conducted by the Society of Digestive Endoscopy of the Chinese Medical Association included 8892 patients with chronic gastritis confirmed by gastroscopy in 10 cities and 33 centers. The results showed that the pathological diagnosis rate of CAG was 25.8%, the endoscopic diagnosis rate was 17.7%, the prevalence rate of IM was 23.6%, and the prevalence rate of dysplasia was 7.3% . In 2016, among the 183,426 patients undergoing gastroscopy at the Peking University Third Hospital from 1989 to 2014, CAG was detected in 22.4% of the patients, the ratio of male to female patients was 1:1.4, and the average age was 59.2 ± 14.1 years .
A European epidemiological study  found that the prevalence of CAG increased with age. In a cohort study of 389 people in South Korea, the prevalence rates of gastric antrum atrophy and gastric body atrophy were 42.5% and 20.1%, respectively. The prevalence rate of CAG increased significantly with age for both men and women .
Some scholars have analyzed the prevalence data from studies of CAG in unselected populations in different countries published before November 2005. Among them, 15 studies confirmed CAG by gastroscopy, and 26 studies confirmed CAG by serum pepsinogen levels. CAG is more common among elderly individuals in different regions of the world. The older population is, the higher the prevalence rate, but there is no obvious sex difference. The incidence rate of CAG in some Asian countries, including China and Japan, is higher than that in other regions of the world .
Statement 2. The occurrence of chronic atrophic gastritis is closely related to H. pylori infection
The occurrence of CAG is closely related to H. pylori infection, and the risk of CAG after H. pylori infection can increase by 4 times [21, 22]. Even in a population with a low- H. pylori prevalence (< 10%), the occurrence of IM and dysplasia is closely related to H. pylori infection. In a population with a high prevalence of H. pylori infection (> 60%), more than 80% of the H. pylori -positive patients had active gastritis or CAG [23, 24]. As reported by Peking University Third Hospital, the H. pylori infection rate in CAG patients was 26.7% .
Statement 3. The sensitivity of white light endoscopy in diagnosing atrophic gastritis is poor, and the coincidence rate with the pathological diagnosis is low
In 2014, a survey conducted by the Society of Digestive Endoscopy of the Chinese Medical Association found that, with pathological diagnosis as the "gold standard", the sensitivity and specificity of the endoscopic diagnosis of atrophy were 42% and 91%, respectively, and the coincidence rate between endoscopic and pathological diagnoses needs to be improved . In a 2006 multicenter study of an asymptomatic population in South Korea (n = 25,536), the prevalence of CAG diagnosed by endoscopy was 27.1%, which was lower than that diagnosed by histology .
Syndrome distribution of gastric precancerous lesions
Statement 4. There is a lack of consolidated standards of gastric precancerous lesions for syndrome differentiation
Most PLGC patients have no specific clinical symptoms or signs, and TCM syndrome differentiation is mainly based on the underlying disease of CAG. Deficiency carried by pathogen factors-and deficiency resulting from excess are important patterns of pathogenesis transformation [25,26,27,28] and consolidated standards of syndrome differentiation are still lacking. A large multicenter cross-sectional study (n = 1000)  suggested that the mixed syndrome of deficiency and excess runs through the whole process of PLGC, while IM occurs in the critical stage of deficiency, converting to an excess syndrome. Another study by the same team (n = 592)  further concluded that the syndrome evolving characteristic of sthenia transforming into asthenia, gradually appeared as yin deficiency and blood stasis during the process of CNAG evolving into CAG, IM, and dysplasia. A cross-sectional study (n = 1056)  pointed out that the syndrome of spleen and stomach weakness has the maximum relevance with gastric atrophy and IM, while the syndrome of stomach meridian blood stasis has the greatest correlation with dysplasia. Another cross-sectional study (n = 307)  also indicated that the syndrome of stomach yin deficiency and stomach meridian blood stasis gradually increased with the progression of gastric atrophy and IM (P < 0.01). Therefore, the development of PLGC is a complex gradual process from the qi to blood, eventually entering the collaterals. Blood stasis and deficiency may be the key syndrome elements in the conversion of deficiency and excess syndromes. However, the relevant conclusions need to be further confirmed by a wide-range, large-sample epidemiological investigation.
Diagnosis and grading
Adequately enough and high-quality preoperative preparation benefits the improvement of the detection of PLGC.
Statement 5. The application of defoaming agents and mucolytic agents can improve the visibility of gastric mucosa, which is helpful for detecting gastric mucosal lesions
A clear visual field of the endoscope is a prerequisite for detecting lesions and performing an accurate biopsy. Excessive gastric mucus and foam can prolong an examination time and cause missed diagnosis and misdiagnosis. The elimination of foam and the application of mucolytic agents are essential to improve the quality of an observation . The improved visibility of the gastric mucosa is beneficial for the detection of minimal gastric mucosal lesions, including precancerous lesions .
A randomized clinical trial (RCT) showed that the amount of foam in the stomach was significantly reduced after the administration of simethicone .
Pronase is widely used in the removal of mucus in the upper digestive tract. The application of pronase during endoscopic washing of the gastric mucosa can reduce the thickness of mucus, which is conducive to biopsy and diagnosis [35, 36]. The combination of pronase and simethicone significantly improved the gastric mucosal visual field score (73% vs. 49%) and reduced the amount of flushing water without increasing the operation time . Domestic studies have shown that simethicone combined with chymotrypsin can increase the detection rate of precancerous lesions and early gastric cancer (36.4% in the test group; 26.8% in the control group, P = 0.000) . Another study (n = 720) showed that the combination of the two reagents could improve the visibility of the gastric mucosa, but there was no difference in the detection rate of lesions between the groups .
Statement 6. When gastric peristalsis severely affects the observation, proper antispasmodic treatment can improve the visual field of observation and facilitate the detection of lesions
For patients with violent gastric peristalsis, which makes it difficult to observe lesions, antispasmodics should be considered . Common antispasmodic methods are as follows: (a) an intramuscular or intravenous injection of 10–20 mg of scopolamine butyrate and an intravenous injection of 1 mg of glucagon; (b) a local spray of 20 ml of 0.8% peppermint oil solution . RCTs have shown that spraying peppermint oil locally has a better antispasmodic effect than intramuscular injections of scopolamine butybromide and has fewer side effects .
At present, there is no research that provides evidence that antispasmodic treatment improves the detection rate of precancerous lesions, and drugs such as scopolamine and glucagon have side effects, so physicians should be cautious in the clinical application of these drugs. However, patients for whom observation is severely affected by gastric peristalsis, proper antispasmodic treatment can ensure a better field of view .
Statement 7. Intraoperative sedatives are recommended for patients with severe anxiety
The purpose of sedation in digestive endoscopy for diagnosis and treatment is to eliminate the anxiety and discomfort of patients, enhance their tolerance and satisfaction, reduce the risk of injury and accidents during the operation, and create the best operating conditions for endoscopists [42, 43]. Patients who are worried or fearful about endoscopy, patients who are highly sensitive and unable to control themselves , and patients who undergo long-term and complicated diagnosis and treatment procedures can be sedated by an anesthesiologist after eliminating contraindications. It should be noted that sedation itself has a high risk. Therefore, medical institutions that perform sedative gastrointestinal endoscopy should meet the requirements for relevant places and equipments, including the area of the diagnosis and treatment unit, complete diagnosis and treatment equipment and monitoring/rescue personnel, drugs, etc. .
Statement 8. Conventional white-light endoscopy could be used for PLGC screening. High-definition conventional chromoendoscopy, virtual chromoendoscopy and magnifying endoscopy should be used for the diagnosis of patients who are at high risk for gastric carcinoma
Conventional white-light endoscopy is the basic method for detecting PLGC; however, the correlation between histological and conventional white-light endoscopic findings for the diagnosis of gastric precancerous conditions is poor. High-definition conventional chromoendoscopy, virtual chromoendoscopy and magnifying endoscopy should be used for the diagnosis of PLGC to improve the accuracy of disease detection. A cross-sectional study showed that high-definition white-light endoscopy (HD-WLE) had a global accuracy of 88% for the diagnosis of IM, with a sensitivity of 75% and specificity of 94% . A real-time multicenter prospective study showed that the global accuracy of HD-WLE for the diagnosis of IM was 83%, with a specificity of 98% but with only 53% sensitivity .
Conventional chromoendoscopy with the application of dyes (indigo carmine, methylene blue, acetic acid, or hematoxylin) can improve the sensitivity and accuracy for the detection of PLGC. A meta-analysis showed a sensitivity and specificity of dye-chromoendoscopy in the detection of PLGC (atrophy, IM and dysplasia) of 90% and 82%, respectively, with these results being significantly better than those of white-light endoscopy alone (P = 0.001) . Virtual chromoendoscopy, which is available at the touch of a button, can avoid the misdiagnosis of lesions caused by uneven dyeing. Compared with conventional chromoendoscopy, virtual chromoendoscopy can shorten endoscopic procedures. The sensitivity and specificity of narrow-band imaging (NBI) with magnification for the diagnosis of IM were 86% and 77%, and for dysplasia/early cancer, these values were 90% and 83%, respectively . A multicenter prospective randomized study showed that even though specificities for IM were the same, the sensitivity for IM (92% vs 59%) were much higher for NBI than for HD-WLE . In a randomized prospective crossover study, the accuracy of IM detection by NBI was significantly higher than that by WLE (P = 0.001) . Linked color imaging (LCI) has high accuracy in the diagnosis of H. pylori infection, and blue laser imaging (BLI) has high accuracy in the diagnosis of atrophy. BLI-ME has high accuracy in the diagnosis of IM. NBI with the application of dyes (indigo carmine, methylene blue, acetic acid) can improve the frequency for the detection of PLGC [52,53,54].
Statement 9. The evaluation and diagnosis of H. pylori infection status should be included in endoscopic examinations
With the deepening of the understanding of H. pylori Japanese scholars have systematically summarized the endoscopic manifestations of H. pylori infection status. The evaluation and diagnosis of H. pylori -uninfected gastric mucosa, H. pylori-infected gastric mucosa or H. pylori -past infected gastric mucosa can be judged through endoscopic findings with reference to the Kyoto classification of gastritis . The criteria for judgment are as follows: (a) H. pylori-uninfected gastric mucosa: regularly arranged collecting venules (RAC) should be observed in normal gastric mucosa on the lesser curvature side from the angular region to the lower gastric body. An enlarged fold, mucosal swelling, and sticky mucus should not be seen in noninfected gastric mucosa; (b) H. pylori -infected gastric mucosa: atrophy, IM, diffuse redness from the fundus to the stomach body, loss of RAC, enlarged fold, mucosal swelling, nodularity, xanthoma, hyperplastic polyp, and sticky mucus are observed; (c) H. pylori -past infected gastric mucosa: atrophic gastric mucosa and/or other current infection features are noted, with the following exceptions: diffuse redness from the fundus to the stomach body, mucosal swelling, sticky mucus, and an enlarged fold. After H. pylori eradication, map-like redness is sometimes observed. Thus, map-like redness indicates past infection with H. pylori.
Statement 10. An adequate number, depth and size of biopsy samples are essential for the accurate diagnosis and evaluation of PLGC
High-quality endoscopy with biopsies is the key to increasing the accuracy of pathological diagnoses and ensuring the repeatability of pathological results, thus playing an important role in the diagnosis and evaluation of PLGC.
The European Society of Gastrointestinal Endoscopy (ESGE) stated in 2019 that CAG and IM are often unevenly distributed throughout the stomach. For the adequate staging and grading of gastric precancerous conditions, at least four nontargeted biopsies of two topographic sites (at the lesser and greater curvature, from both the antrum and the corpus) should be taken, and additional targeting biopsies of suspicious lesions should be taken . The British Society of Gastroenterology (BSG) guidelines of 2019 recommended that patients with image-enhanced features of CAG undergo biopsies for confirmation of the endoscopic diagnosis; biopsies are directed at mucosal sites within the Sydney protocol areas. Biopsy samples should be labeled either directed or random to corroborate endoscopic staging assessments. Meanwhile, it also recommended that patients with LGD undergo a second endoscopy with enhanced imaging and extensive biopsy sampling, followed by repeat endoscopy within 1 year. If patients are diagnosed with HGD, they should undergo an immediate second endoscopy with enhanced imaging and extensive biopsy sampling. Extensive biopsy should also be performed for patients with an endoscopic suspicion of CAG, IM or early gastric neoplasia . The Chinese Digestive Endoscopy Association consensus of 2014 and the 2017 pathology group of the Chinese Digestive Society recommended that for patients suspected to have CAG, biopsies should be taken at the incisura, the lesser and greater curvature from the antrum (2–3 cm away from the pylorus), and the lesser and greater curvature from the corpus (8 cm away from the cardia) [57, 58]. Excluding the number of biopsy specimens, the depth and size of the biopsy sample must be sufficient to reach the lamina propria layer .
J. G. Lash  evaluated 400,738 gastric biopsy sampling sets and reported that the acquisition of at least two biopsy specimens from the antrum and corpus, essentially following the Sydney System recommendations, is a sensible strategy that guarantees the maximum diagnostic yield for the most common gastric inflammatory conditions. Meanwhile, in a prospective study from a single center, a total of 1080 biopsies from 176 patients were investigated and it was found that obtaining 4 specimens may be sufficient for the accurate diagnosis of a depressed/ulcerative or polypoid gastric lesion, regardless of its histological stage. For infiltrative lesions, at least 5 to 6 biopsies per lesion, with more representative sampling from thickened mucosal folds, may be preferable . Endoscopists with a higher biopsy rate had a lower risk of missed cancer and a higher PLGC diagnosis rate . If CAG and IM lesions are suspected, biopsies should be taken from the antrum and corpus. Adequate numbers, depths and sizes of biopsy samples are essential for the accurate diagnosis and evaluation of precancerous lesions of gastric cancer.
Statement 11. Targeting biopsy of suspicious lesions is conducive to the evaluation of curative effects and follow-up monitoring
The sensitivity of endoscopy in the diagnosis of PLGC is low, and the pathological examination of biopsy samples is often needed to confirm the diagnosis. Due to the lack of accurate localization marks in the gastric mucosa, it is very common to perform biopsies from different positions and the diagnosis of lesions may be missed in routine endoscopic examinations. The marking targeting biopsy (MTB) uses specially designed calibrated biopsy forceps for biopsies, and it can perform biopsies and identify the positions of lesions at the same time . The method is safe, effective and easily used in operations [63,64,65]. It was reported that the effective rate of marked gastric localization was higher than 95% after 12 months; after 2 years of follow-up, there was no statistical significance in the occurrence rate of gastric wall calibration marks. This result suggested that the calibration marks can be retained in the gastric wall for more than 2 years . For chronic gastritis patients with OLGA/OLGIM stage III/IV or patients with a high score of gastric cancer screening, marking targeting biopsy is recommended for suspected lesions .
Statement 12. Additional biopsies are required for visible lesions and suspected neoplastic lesions under endoscopy
High discrepancy rates existed between endoscopic forceps biopsy and resected specimen for forceps biopsy, which is limited by its superficiality and small specimen size , while multiple biopsies can improve the diagnostic accuracy . Therefore, additional biopsies were necessary to increase the diagnostic accuracy for suspicious lesions. The number of biopsies for lesions suspected to be early gastric cancer is still not unified. According to the 2014 version of the Consensus of our country on early gastric cancer screening and endoscopic diagnosis and treatment, the number of biopsies for suspected early gastric cancer lesions depends on the size of the lesions. If the maximum diameter of the lesions is > 1 cm, the number of specimens should be ≥ 2; for lesions > 2 cm, the number of specimens should be ≥ 3; and for lesions > 3 cm, the number of specimens should be ≥ 4 . Multiple biopsies were related to a high risk of biopsy-induced ulcers, bleeding, and local fibrosis after multiple biopsies, which may increase the difficulty of endoscopic treatment and raise the risk of adverse events. In addition, local fibrosis may lead to a negative lift sign during endoscopic treatment, resulting in misjudgment of the lesion depth and affecting the selection of treatment options. Therefore, the consensus of our country in 2017 proposed that, for gastric mucosa suspected to be early neoplastic lesions, one to two biopsy samples for lesions less than 2 cm and an additional biopsy should be obtained for every 1 cm increase in diameter was recommended . A retrospective study in Japan found that the diagnostic accuracy of two biopsies for early gastric cancer was 92.5%, which was significantly higher than that of 83.9% for one biopsy, irrespective of tumor size; however, the diagnostic accuracy did not significantly differ between two and three or more biopsies. Therefore, this study indicated that two biopsies was the optimal number required to diagnose early gastric cancer . With the application of more powerful image-enhanced endoscopic techniques, such as magnifying endoscopy with narrow-band imaging (M-NBI), it is possible to avoid unnecessary biopsies and reduce the number of biopsies [71, 72], but the optimal number of endoscopic biopsy specimens for suspicious lesions still needs to be further explored.
Pathological diagnosis and evaluation
Statement 13. Standardizing the protocol of biopsy specimen processing will help improve the accuracy of pathological diagnosis 
The standardized protocol for biopsy specimen processing is as follows: (a) after removing the biopsy tissue, the base should be adhered to a small piece of filter paper and then immersed in fixative. The volume of the fixative should be 10 times or more that of the specimen. Generally, 4% neutral buffered formalin is used for fixation for 6 to 48 h; (b) the specimens of different parts must be separated into different bottles and labeled clearly. The bottle should be transparent, drop-resistant, and have a wide/screw-mouth; (c) when receiving the specimens, the content of the application form and the labeling information of the bottle must be checked and rechecked carefully. Whether there is tissue in the bottle, and the number of tissue blocks, must be clarified; (d) the pathologist disposing of the material needs to drop eosin dye solution on the specimen and then wrap the specimen with filter paper, or a technician adds eosin dye solution to the tissue processor to observe the structure and direction of the tissue during embedding; (e) attention should be paid to the direction of the tissue when embedding, and the tissue should be placed sideways and fixed in paraffin to ensure that the mucosal layer, muscular mucosa layer, and submucosal layer are all included when sliced; (f) the instruments, blades, tweezers, countertops, and the water surface should be cleaned timely after one block is sliced to prevent misdiagnosis caused by contamination; (g) at least 6 continuous slices should be cut from the block and collected on the same glass slide.
Statement 14. Subtyping incomplete intestinal metaplasia has clinical significance [74,75,76,77]
Subtyping IM is usually based on morphological changes and mucin variety. Neutral mucin, sialic acid mucin and sulfated mucin can be distinguished by AB/PAS staining (Alcian Blue, pH 2.5/Periodic Acid Schiff) and HID/AB staining (High Iron Diamine/Alcian Blue, pH 2.5). According to the different mucins secreted by different cells, IM is classified into three types: type I, type II, and type III. Type I is complete metaplasia, and type II and type III are incomplete metaplasia. Previous studies have shown that type III (incomplete type) IM is associated with an increased risk of gastric cancer.
Considering that histological subtyping is helpful in assessing the risk of gastric cancer and has potential value for estimating therapeutic results and prognosis, it is advisable to identify type III IM at a minimal cost and workload. Of course, when complete GIM is found in the specimen, it should not be ignored. We need to improve the data and evidence to clarify the significance of the histological subtyping of GIM and establish the best clinical practice for the management of gastric precancerous lesions [78, 79].
Statement 15. Gastric dysplasia needs to be differentiated from reactive hyperplasia
When it is difficult to determine the nature of the disease as dysplasia or reactive hyperplasia, the diagnostic accuracy can be improved by the following methods: (a) continuous deep section of the tissue block, immunohistochemical staining, histochemical staining, and interoffice consultation may be helpful; (b) cases that cannot be diagnosed can be classified as indefinite for dysplasia; (c) Experienced pathologists in gastrointestinal pathology can be consulted [80, 81].
Mucosa syndrome differentiation under gastroscopy
Statement 16. Mucosal syndrome differentiation under gastroscopy is an extension of inspection in traditional Chinese medicine. It focuses on discriminating gastric mucosal lesions. It is an important reference for the overall syndrome differentiation of traditional Chinese medicine and an objective basis for guiding local treatment 
Mucosal syndrome differentiation under gastroscopy belongs to the category of local syndrome differentiation and is a diagnostic method used to determine the pathogenesis and syndrome by analyzing the mucosa color, morphology, folds, secretion, peristalsis, microvessels, etc. By discriminating mucosal changes and other lesions before and after H. pylori eradication, a reasonable local application of a medication regimen can be formulated, which is also an important supplement to the overall syndrome differentiation. Due to the lack of evidence from high-quality prospective cohort studies, we referred to the syndrome differentiation criteria under gastroscopy from the Consensus of TCM Diagnosis and Treatment Experts of Chronic Gastritis (2017) (Table 2).
Statement 17. Patients with dysplasia found on random biopsy should be re-evaluated by high-definition virtual or dyeing chromoendoscopy. If no visible lesions are found in the re-evaluation, the patient should be monitored once again by high-definition virtual or dyeing chromoendoscopy, with an interval of 6–12 months
High-definition virtual or stained endoscopy can improve the detection rate of dysplasia. A study included 20 patients with dysplasia or gastric cancer. Conventional endoscopy did not find visible lesions, but high-definition virtual or stained endoscopy found visible lesions in 18 of the patients . Random biopsy found that the patients with dysplasia had a significantly higher risk of cancer, and the annual incidence of gastric cancer was as high as 6% . Patients with dysplasia found during random biopsy should immediately go to a high-level endoscopy center for reassessment with high-definition virtual or dyeing chromoendoscopy. If high-quality endoscopy does not find clearly visible lesions, it is recommended the gastritis be staged by biopsy and high-quality endoscopic monitoring be performed every 6 months (HGD) to 12 months (LGD).
Statement 18. Screening and monitoring of dysplasia under endoscopy should be given great attention
A recent meta-analysis showed that the incidence of gastric cancer in patients with dysplasia is 40.36 cases/1000 person-years . An endoscopic submucosal dissection (ESD) case series study showed that 24.0% and 52.7% of LGD and HGD patients, respectively, had histological deterioration after resection . A meta-analysis found that 25% of the LGD patients had an escalation in pathological staging after resection, and 6.9% of them had malignant transformation . A domestic study with a 10-year follow-up showed that 51.0%-78.7% of the LGD patients had reversal, and another 0.45%-14.3% had cancer . In summary, for patients with dysplasia found under endoscopy, the screening and monitoring of visible lesions should be strengthened to detect and treat early gastric cancer.
Statement 19. Patients with uncertain dysplasia diagnosed by non-targeted biopsy can benefit from reevaluation with endoscopic examination
The biopsies of some tumorous lesions may be negative. One study  found that in 26.8% of the patients with indefinite neoplasm/dysplasia (IFND) on preoperative biopsy, 5.0% of the lesions were diagnosed as adenomas after resection, and 21.8% were diagnosed as early gastric cancer. In another study, 3 gastrointestinal pathologists reassessed IFND biopsy specimens, and a total of 11/46 patients were diagnosed with dysplasia (10 cases of LGD and 1 case of HGD) . A retrospective study included 129 patients with IFND who underwent OLGA staging. The median follow-up was 31 months. Twenty-five OLGA stage III/IV patients were followed up, and 6 cases of LGD or HGD were found . Therefore, patients diagnosed with IFND in non-targeted biopsy can benefit from re-evaluation with endoscopic intensive examination in centers with experience in early gastric cancer diagnosis and endoscopic treatment.
Statement 20. In patients with high-grade dysplasia, immediate high-quality endoscopic reassessment with Chromoendoscopy (virtual or dye-based) is recommended to determine whether endoscopic or surgical treatment should be performed
Patients with HGD have a high risk of simultaneous invasive cancer or the rapid progression of lesions . In a group of PLGC patients, approximately 25% of the HGD patients were diagnosed with gastric cancer during the 1-year follow-up period . The latest meta-analysis showed that the highest incidence of gastric cancer in patients with HGD was 186.40/1000 person-years, and that in patients with LGD and IFND was 11.25/1000 person-years . Gastroscopic and histological reassessment should be performed immediately for patients with HGD, and endoscopic or surgical treatment is recommended for endoscopic visible lesions .
CAG and IM
CAG and IM are independent risk factors for gastric cancer [93,94,95,96]. A Japanese study  showed that the cumulative 5-year incidence rates of gastric cancer of extensive CAG and IM were 1.9 ~ 10% and 5.3 ~ 9.8%, respectively. Patients with extensive atrophy or IM (antrum and corpus) or OLGA stage III/IV or OLGIM stage III/IV had a higher risk of progression to gastric cancer.
Statement 21. Patients with high-risk atrophic gastritis should be followed up with high-quality endoscopy or white-light endoscopy combined with biopsy every year, especially those with a family history of gastric cancer, who need more intensive follow-up.
Extensive atrophy or IM (antrum and corpus) was associated with a higher risk of progression to gastric cancer than single-site lesions [97,98,99]. OLGA stage III/IV, OLGIM stage III/IV, and endoscopically classified moderate-to-severe atrophy were significantly more frequent in the paracancerous tissues of gastric cancer . OLGA stage IV, histological IM, and a higher classification of endoscopic atrophy were identified as independent risk factors for gastric cancer . Ten percent of gastric cancer patients present familial aggregation . The risk of progression to cancer in patients with first-degree relatives with gastric cancer increased by 2–10 times . The risk of progression to cancer in patients with second-degree relatives with gastric cancer was also higher but was lower than that in patients with first-degree relatives . The study found that patients with IM and a family history of gastric cancer progressed faster .
Therefore, it is recommended that the abovementioned patients be assessed with high-quality endoscopy every year, especially those with a family history of gastric cancer, who need more intensive follow-up.
Statement 22. Patients with low-risk atrophic gastritis should be followed up with endoscopy every 3 years, and those with a family history of gastric cancer should be followed up every 1–2 years
A study including 27,777 patients found that the incidence of gastric cancer was associated with the extent of atrophy: C-1 0%, C-2 0.3%, C-3 0.7%, O-1 1.3%, O-2 3.70% and O-3 5.3% . Patients with mild atrophy restricted to the antrum have a relatively lower risk of developing gastric cancer. Endoscopy or serological screening is recommended every 3 years for these patients, but follow-up every 1–2 years follow-up is recommended for those with a family history of gastric cancer.
Statement 23. Patients with autoimmune gastritis may benefit from endoscopic follow-up every 3 years
Autoimmune gastritis is often accompanied by vitamin B12-deficiency anemia, which is known as pernicious anemia. The risk of pernicious anemia-related tumors (including gastric carcinoma and neuroendocrine tumors) is significantly increased .
Comparing 1,138,390 pernicious anemia patients to 100,000 matched individuals, it was found that individuals with pernicious anemia were at increased risk for noncardiac gastric adenocarcinoma (OR = 2.2, 95% CI 1.9–2.5) and gastric carcinoid tumors (OR = 11.4, 95% CI 8.9–14.7) . A total of 21,265 patients with pernicious anemia were followed up for an average of 7.1 years , and it was found that the excess risk for gastric cancer distal to the heart increased with increasing follow-up duration. A recent meta-analysis with 27 studies and a total of 22,417 patients showed that the calculated pooled gastric cancer incidence rate was 0.3% per person-year, and the overall relative risk for gastric cancer in pernicious anemia patients was 6.8 (95% CI 2.6–18.1) .
Some studies showed that the greatest risk of gastric cancer in patients with pernicious anemia was in the first year of follow-up [110, 111]. One study  performed follow-up gastroscopies 3 years after the primary screening examination of 56 patients and identified 2 patients with gastric adenocarcinoma on follow-up. Another study  followed up a group of 27 patients for 6 to 7 years, and none of the patients developed gastric cancer. One study randomly assigned 24 patients to a 24- or 48-month follow-up interval, and gastric cancer was not found in either group . Based on the above studies, we recommend follow-up endoscopy at 3-year intervals in patients with autoimmune gastritis.
Noninvasive screening methods
Statement 24. PGI, PGI/II (PGR), G-17 and H. pylori -IgG can be used to screen CAG patients at high-risk of gastric cancer from general population
A cross-sectional study of 14,929 patients in China found that  the serum marker PGI/II ratio and G-17 and H. pylori -IgG expression were independently associated with the risk of gastric cancer (p < 0.05). A meta-analysis  included 20 studies and the overall sensitivity of PG, G-17, and H. pylori -IgG expression in the combined diagnosis of CAG was 74.7%, and the specificity was 95.6%. Another meta-analysis  showed that the overall sensitivity of PG I, the PG I/II ratio, G-17, and H. pylori -IgG expression in the combined diagnosis of gastric atrophy was 70.2%, and the specificity was 93.9%. Their sensitivity in the combined diagnosis of antral atrophy was 51.6%, and their specificity was 84.1%. For patients with a high risk of the combined detection of PG I, the PG I/II ratio, G-17, and H. pylori -IgG expression, further endoscopy should be performed.
Statement 25. Histological and serological MG7 testing can be used to assist in the screening of groups at high-risk of gastric cancer
MG7 is a specific monoclonal antibody for gastric cancer with high specificity and sensitivity. A number of studies have found that the expression level of MG7 antigens (MG7Ag) gradually increases in superficial gastritis, CAG, IM, dysplasia and gastric cancer [118,119,120]. The positive ratio of MG7Ag in noncancer patients was 3.0%-5.6%, and that in gastric cancer patients was 77.5%, suggesting that MG7Ag has an early alerting effect for gastric cancer. A study involving 2710 patients found that  the sensitivity of MG7Ag immuno-PCR for the diagnosis of gastric cancer was 77.5%, the specificity was 95.6%, and the accuracy was 73.12%. Histological or serological MG7Ag-positive patients are high-risk groups for gastric cancer and should undergo precise endoscopic examinations.
Risk monitoring of precancerous lesions of gastric cancer by combining disease and syndrome
Statement 26. In carrying out risk monitoring and management with integrated traditional Chinese and Western medicine, in addition to serology, the Kimura-Takemoto classification, OLGA/OLGIM risk assessment, and TCM syndromes can be included
Syndromes are an important reference content for TCM diagnosis and treatment of diseases. The TCM syndromes of CAG and PLGC are related to the risk of cancer. The Kimura-Takemoto classification of endoscopy assesses the extent of gastric mucosal atrophy, among which the open type (type O) is associated with a higher risk of gastric cancer . A study(n = 347)  found that the proportion of open-type CAG patients with insufficient gastric yin syndrome (19.1%), liver stomach stagnation-heat type (17.0%), gastric-collateral stasis syndrome (16.2%), and spleen stomach weakness syndrome (11.3%) was higher. A study  on the correlation analysis between the serum PGI/II ratio (PGR) and TCM syndrome types in 126 CAG and PLGC patients found that strong PG positivity was common in patients with gastric collateral stasis syndrome (28.6%) and spleen stomach weakness syndrome (25.0%). Severe gastric mucosal atrophy and PLGC are the most common syndromes of gastric collateral stasis and spleen and stomach weakness, which are considered to be high-risk syndromes of clinical cancer. A study  used logistic regression to analyze the correlation between TCM syndrome types and gastric cancer risk in 180 CAG patients showed that the TCM syndrome types were significantly related to the increased risk of OLGA, especially gastric collateral stasis syndrome (OR = 1.0 95% CI 1.6 ~ 60.7). Gastric collateral stasis may be one of the factors that aggravates disease progression. Therefore, on the basis of serology, the Kimura-Takemoto classification of endoscopy, OLGA and OLGIM risk assessment, and TCM syndromes can be included for risk assessment and management with integrated TCM and Western medicine . The current research focuses on small single-center samples, and the relevant conclusions need to be further confirmed by epidemiological investigations and studies with large-scale samples from multiple centers.
Orientation of intervention
Statement 27. Atrophy, intestinal metaplasia and obvious active inflammation can be treated by eradicating H. pylori (if positive) and the short-term use of proton pump inhibitors (PPIs) or gastro-protecting agents
Active inflammation is an important factor in the progression of CAG. The causes of active gastric mucosal inflammation include H. pylori infection, bile reflux, drugs, diet and certain kinds of lifestyles. The purposes of treatment are to eliminate the causes, relieve the symptoms and reduce gastric mucosal inflammation . The available treatments include the eradication of H. pylori and application of mucosa-protecting agents. Studies have confirmed that after the success of H. pylori eradication therapy, neutrophil infiltration in the gastric mucosa disappears, and inflammation is quickly relieved . Ten years after eradication, IM and atrophy can also be improved significantly , which helps to prevent or delay the further development of atrophy and IM . Additionally, for CAG patients with active inflammation, the degree of inflammation could be significantly reduced with the application of PPIs [129, 130] or gefarnate . Therefore, we recommend that patients with atrophy, IM and active inflammation be offered H. pylori eradication therapy (if they test positive) and the short-term use of PPIs or mucosa-protecting agents.
Statement 28. Chronic atrophic gastritis of the operative link on gastric atrophy (OLGA) and operative link on gastric intestinal metaplasia (OLGIM) stages III/IV are targets of internal medicine interventions
The OLGA/OLGIM grading and staging systems proposed by the International Group of Gastrointestinal Pathologists (Atrophy club) for the evaluation of gastric mucosal atrophy and IM are based on biopsy pathology and are divided into stages 0–IV. OLGA/OLGIM stages III/IV are dependent risk factors for gastric cancer . The risks of gastric cancer in OLGA and OLGIM high-risk groups increased by 19.9 times and 38.2 times, respectively . In a prospective cohort study of 1755 patients with a long-term follow-up, neoplastic lesions were only found in the OLGA stages III/IV group . Therefore, OLGA/OLGIM stages III/IV are targets of internal medicine interventions.
Statement 29. Medical intervention is required for low-grade dysplasia, and endoscopy treatment is required for high-grade dysplasia and some low-grade dysplasia with visible lesions
LGD lesions are partially reversible and have been documented to spontaneously regress in 38 to 75% of cases and persist in 19 to 50% of cases. A total of 0 to 15% of LGD lesions progressed to HGD lesions or gastric carcinoma within 10 to 48 months . The risk of HGD progression to gastric carcinoma is as high as 60–85%, with a median time of 4–48 months. In the first year of the initial diagnosis . The discrepancy rate of the pathological diagnosis of LGD between endoscopic forceps biopsy and endoscopic resection was as high as 28.5%, and approximately 25% of LGD diagnosed with endoscopic biopsy was histologically upgraded after endoscopic resection, including gastric HGD (16.7%) and gastric carcinoma (6.9%) . The risk factors for pathological diagnosis of LGD upgraded after endoscopic resection are [136,137,138,139] as follows: (a) endoscopic findings: a lesion size ≥ 10 mm, with surface redness, nodules, central depression, surface erosion or ulcers, located in the upper 1/3 of the stomach; ME-NBI showed clear demarcation line of the lesion, abnormal microstructure of the glandular opening and/or microvessels; (b)pathological characteristics: biopsy pathology indicated villous tubular or villous tissue in the lesion, and the positive expression of MUC6; (c) serology: H. pylori -CagA positivity, a decreased serum PG I/II ratio and hypergastrinemia; (d) other: aged > 45 years old, a family history of gastric cancer, people in areas with a high incidence of gastric cancer, residual stomach, etc.
Therefore, it is recommended that treatment and follow-up programs be required if patients have visible LGD lesions, HGD or carcinoma by endoscopy examination. If there is no visible lesion, but there is a histological showing of dysplasia by random biopsy, it is recommended that high-definition endoscopy or chromoendoscopy be used to reassess as soon as possible. If no lesions are found, regular endoscopic surveillance should be performed. If HGD was found, re-examination by endoscopy should be performed within 6 months. If LGD was found, re-examination should be performed within 12 months [5, 140, 141].
Statement 30. Surveillance and interventions should be included for indefinite for neoplasm/dysplasia lesions, and pathological consultation can be conducted. A biopsy can be repeated, if necessary, to confirm the diagnosis
IFND (indefinite for neoplasm/dysplasia) lesions are classified as Category 2 lesions according to the revised Vienna classification. It is not a final diagnosis in pathology but a classification when the morphological phenotype is indefinite [5, 56, 58]. IFND lesions are usually described in pathology reports either as neoplastic or nonneoplastic (reactive), which indicates regenerative atypical epithelia or atypical glands/cells [56, 142, 143]. The diagnosis of IFND is related to the quality of the biopsy. When the initial diagnosis is FIND lesions, a pathologist should first make a deep or serial pathological section, and if necessary, add Ki-67, p53 and other immunohistochemical stains to assist in diagnosis. Meanwhile, a consultation with pathologists should be conducted to improve the quality of diagnosis [5, 56, 58]. If a diagnosis is still not confirmed, a second high-quality biopsy should be performed [88, 142,143,144]. High-quality biopsy can be achieved in two ways: first, the number and size of the biopsies, which are limited to large lesions, should be increased; second, the resolution and clarity of the endoscopy, such as image enhancement endoscopy, should be increased to acquire a more accurate biopsy. Clinicians should combine ordinary white light endoscopy and magnifying endoscopy to observe the characteristics of the lesion, perform an accurate biopsy, and discuss with pathologists, if necessary, to confirm the diagnosis. The subsequent diagnosis and treatment are determined according to the type of final pathological diagnosis. If the lesion is too small to repeat the biopsy, endoscopic mucosal resection can also be applied to confirm the diagnosis [88, 142, 143].
Statement 31. Patients with HGD or early gastric cancer can be treated with a combination of Chinese and Western medicine after endoscopic treatment
There is a certain risk of delayed bleeding of artificial ulcers after the endoscopic resection of HGD and early gastric cancer. Acid suppressive drugs should be used prophylactically after the operation. At present, PPIs are often used as the first choice to prevent bleeding and promote ulcer healing. In China, most doctors recommend the continuous use of standard-dose PPIs for 4–8 weeks. For patients with risk factors for delayed healing of artificial ulcers after gastric ESD, the dosage of PPIs can be increased, the course of treatment can be prolonged or gastric mucosal protective agents can be added as appropriate . As a further intervention after endoscopic therapy, traditional Chinese medicine preparation has been proven to be effective by many studies. Kangfuxin liquid has a protective effect on gastric mucosal injuries after endoscopic surgery and can effectively reduce bleeding [146,147,148]. Jianweiyuyang tablets have a therapeutic effect on iatrogenic ulcers [149, 150].
H. pylori infection in patients with early gastric cancer should be timely eradicated after endoscopic treatment . Bismuth quadruple is currently recommended as the main eradication plan . There is still a certain failure rate in the eradication of H. pylori by Western medicine. It has been reported that traditional Chinese medicine “sensitizes” other drugs and “reverses” bacterial resistance [152, 153]. Studies have shown that standard triple and quadruple therapy combined with traditional Chinese medicine antibacterial therapy can improve the eradication rate of H. pylori [154, 155]. Moreover, traditional Chinese medicine can significantly improve clinical symptoms, reduce adverse drug reactions and increase patient compliance. Therefore, for patients with drug-resistant bacteria or obvious side effects, the combination of traditional Chinese and Western medicine can take full advantages of both approaches and better solve the problem of H. pylori infection .
There is still a potential risk of recurrence for patients with early gastric cancer who have achieved curative resection or are relatively close to curative resection. The local recurrence rate is 0.13–1.3%, and the incidences of synchronous cancer and metachronous cancer are 4.0%-12.9% and 2.5–5.1%, respectively. The cumulative risk rates at 5 years, 7 years and 10 years are as high as 9.5%, 13.1% and 22.7% , respectively, so standardized follow-up and interventions are needed. CAG, IM and LGIN are often found in these patients. Modern medicine mainly provides H. pylori eradication and mucosal protection treatment and lacks ideal intervention measures to improve the pathological state of the stomach. At present, there are many reports on the treatment of PLGC with traditional Chinese medicine preparations [157, 158]. It was found that the combination of traditional Chinese medicine and Western medicine can better improve gastric atrophy, IM and dysplasia.
Eliminating the risk factors
Statement 32. There is no definite evidence that PPIs can induce or aggravate gastric precancerous lesions such as atrophic gastritis or intestinal metaplasia, but the long-term use of PPI preparations is not recommended in clinical practice
In 2014, a survey of 8892 patients with chronic gastritis from 33 endoscopy centers showed that the detection rates of CAG, IM, and dysplasia were 25.8%, 23.6%, and 7.3%, respectively. PPIs were the most commonly used drugs in the above population . It was shown in a RCT from Europe that acid-suppressive therapy in the form of PPIs maintained for 3 years facilitated neither the development of gastric glandular atrophy of the corpus mucosa nor the occurrence of IM in GERD patients . Two meta-analyses based on RCTs found that, compared with placebo or H2 receptor inhibitors, the incidence of CAG or IM in patients with long-term use of PPIs did not show significant differences [160, 161]. The use of PPIs can significantly reduce the detection rate of H. pylori , and another study  showed that acid suppression may delay the recovery of gastric mucosal atrophy after H. pylori eradication. A recent study  from South Korea showed a 1.4 times increased risk of gastric cancer in patients who used PPIs ≥ 30 days. Therefore, the long-term use of PPI preparations is generally not recommended for patients with chronic gastritis unless there are clear indications.
Statement 33. A high-salt diet is a risk factor for gastric precancerous lesions. Patients with gastric precancerous lesions should avoid high-salt and pickled foods
The conclusions on the relationship between diet and gastric cancer were not consistent, but most studies showed that a high-salt diet is a risk factor for PLGC [165,166,167,168,169]. People who eat salted meat, or consume a high-salt diet for a long time, have a significantly higher risk of IM . A study  from South Korea reviewed data from 60,261 adults who underwent gastroduodenoscopy as part of a health check-up and found that a salty diet was a risk factor related to PLGC in people ≥ 40 years of age. Another study  found that 24 h urinary sodium excretion was significantly increased in CAG patients with IM. A significant increase in the risk of disease progression was found in PLGC patients who consumed a high-sodium diet [168, 169], and this correlation was more obvious in people with H. pylori infection . Studies [170, 171] from the Chinese population showed that a high-salt diet is a high-risk factor for IM and dysplasia, and its correlation with distal gastric dysplasia is more significant.
Statement 34. A history of long-term smoking significantly increases the risk of the occurrence and progression of gastric precancerous lesions. Patients with gastric precancerous lesions should quit smoking
A number of studies [172,173,174] have suggested that smoking is closely related to PLGC. A case–control study of American veterans showed that smoking was an independent risk factor for IM . This finding was also supported by another case–control study from the northwestern part of China . A study involving 7302 Chinese patients with chronic gastritis also suggested that smoking was an independent risk factor for the occurrence of PLGC . In a study  from South Korea in which 199,235 patients without IM were followed up, a dose-dependent increase in the risk of IM in smokers was found, and this risk was significantly reduced in those who had quit smoking. This dose-dependent correlation was also confirmed in other studies [177, 178].Smoking is not only related to the occurrence of PLGC but also to disease severity. Long-term smokers exhibited a significantly increased risk of severe CAG and IM [179,180,181].
Statement 35. Bile reflux is a risk factor for intestinal metaplasia, and interventions targeting bile reflux may be beneficial to block the occurrence and progression of gastric precancerous lesions
An increased concentration of bile acid was found in the gastric juice of patients with IM , and the incidence of IM and the degree of gland atrophy were also significantly increased in patients with bile reflux . Multiple clinical studies have shown that bile reflux results in a significantly higher risk of IM [184,185,186]. A study involving 30,465 patients who underwent a gastroscopy examination showed that bile reflux is a risk factor for gastric cancer and precancerous lesions . Subsequent cross-sectional and prospective studies  further showed that bile reflux is an independent risk factor for gastric cancer and precancerous lesions.
The risk of bile reflux was found to be increased in patients with IM . A multicenter RCT  from China showed that bile reflux could be relieved when CAG, IM, and dysplasia were improved or reversed. These findings suggested that interventions targeting bile reflux may be helpful in reversing PLGC.
Eradication of H. pylori
Statement 36. The eradication of H. pylori can prevent or slow down the occurrence and progression of atrophic gastritis, thus reducing the risk of gastric cancer
In 1994, the WHO pointed out that H. pylori is a Class I carcinogen for gastric cancer and the most important controllable risk factor for gastric cancer prevention. The eradication of H. pylori can improve gastric mucosal inflammation, delay or prevent the progression of precancerous lesions, and partially reverse atrophy, thus reducing the risk of gastric cancer [136, 191]. Many large-scale, long-term and prospective clinical studies in China and abroad have shown that [192,193,194] the eradication of H. pylori can significantly prevent gastric cancer, and the longer the follow-up time is, the better the prevention effect. A meta-analysis including 6 high-quality RCTs  showed that H. pylori eradication as a primary preventive measure for gastric cancer is more in line with health economics standards in East Asian countries such as China and Japan. An effective treatment time is before atrophy or IM occurs.
A single-center, double-blind, placebo-controlled intervention study in 2020  confirmed that H. pylori eradication can significantly reduce the risk of gastric cancer among H. pylori -infected people with a family history of gastric cancer in first-degree relatives.
Statement 37. The eradication of H. pylori in patients with gastric mucosa atrophy and intestinal metaplasia can reduce the risk of gastric cancer to varying degrees, but regular follow-up should be performed
Most studies have shown that eradication of H. pylori has difficulty reversing IM. A meta-analysis  showed that eradication of H. pylori had no significant preventive effect on CAG patients who had IM or dysplasia. However, the Shandong Linqu study showed  that the incidence of gastric cancer in the H. pylori eradication group and placebo group during 14.7 years of follow-up was 3.0 and 4.6%, respectively , and further confirmed that even if the patient has entered the stage of IM or dysplasia, the eradication of H. pylori has a certain effect on preventing gastric cancer . Studies from Sweden  and Hong Kong, China , have also shown that long-term follow-up can show that H. pylori eradication has the effect of preventing gastric cancer in long-term follow-up. Therefore, for patients with atrophy and IM, the eradication of H. pylori can reduce atrophy and inflammation, delay the further development of IM, and reduce the risk of gastric cancer to varying degrees. However, for these patients, attention should be given to follow-up after H. pylori eradication treatment. Predicting the risk of gastric cancer through the OLGA and OLGIM staging systems or combined pepsinogen (PG) is suitable for screening populations at high-risk of gastric cancer  and then targeted and active endoscopic follow-up should be conducted.
Statement 38. H. pylori eradication therapy after endoscopic treatment of early gastric cancer or high-grade dysplasia can effectively prevent metachronous gastric cancer
Endoscopic mucosal resection (EMR) and ESD are currently the first choice for the treatment of early gastric cancer or HGIN, but the annual incidence rate of metachronous gastric cancer after endoscopic treatment is approximately 3%. Some studies have found that H. pylori eradication after the endoscopic treatment of early gastric cancer may reduce the risk of metachronous tumors . There are also studies showing that H. pylori eradication after the endoscopic treatment of gastric neoplasms cannot reduce the occurrence of metachronous gastric cancer [201, 202]. A large, long-term, prospective RCT  found that the endoscopic resection of early gastric cancer or HGD can effectively reduce the occurrence of metachronous cancer (HR = 0.5, 95% CI 0.3–0.9).
Statement 39. some Chinese patent medicines can be used in the treatment of H. pylori
At present, there are few high-quality studies on the combination of traditional Chinese and Western medicine in the treatment of H. pylori, and most of the results are not credible due to methodological defects. Two RCTs evaluated the effect of Jinghua Weikang capsules in the adjuvant treatment of H. pylori. Jinghua Weikang  capsules combined with PPI triple therapy and quadruple therapy for 10 days showed no significant difference between the two groups (RR= 0.9, 95% CI 0.8-1.1). Another study  compared Jinghua Weikang capsules combined with quadruple therapy and quadruple therapy alone for 10 days, and the curative effect was not obvious (RR=1.1, 95% CI 0.9~1.2). Therefore, Jinghua Weikang capsules combined with PPI triple therapy is similar to quadruple therapy in terms of H. pylori eradication rates. Jinghua Weikang capsules can be used in the clinical setting instead of bismuth agents but cannot significantly improve the H. pylori eradication rate if combined with quadruple therapy. Another RCT included 196 cases of H. pylori -related chronic superficial gastritis  and showed that there was no significant difference in the H. pylori eradication rate between Weifuchun combined with quadruple therapy and quadruple therapy alone (RR = 1.1, 95% CI 1.0-1.2).
Folic acid, antioxidant vitamins
Statement 40. Folic acid, antioxidant vitamins, etc. may delay the process of atrophic gastritis in some people, thus reducing the risk of gastric cancer
A meta-analysis  found that the intake of fruits (RR=0.8, 95% CI 0.7–0.9) and vegetables (RR=0.9, 95% CI 0.7–1.1) was negatively correlated with the incidence of gastric cancer, and the preventive effect was more significant after ≥ 10 years of follow-up.
In the general population, the intake of certain vitamins may reduce the risk of gastric cancer (RR=0.8, 95% CI 0.7–0.8) . Another large cohort study  showed that multivitamins did not reduce the incidence of gastric cancer. A randomized intervention study in 2019  showed that 3365 patients in Linqu, Shandong Province, China, were given H. pylori eradication treatment, vitamin supplements (vitamin C, E and selenium, intervention for 7.3 years), an allicin intervention (7.3 years) and a placebo treatment. After follow-up for 22 years, it was found that 2 weeks of anti- H. pylori treatment and 7 years of vitamins significantly reduced the risk of gastric cancer, and the mortality rate of gastric cancer in the three groups was also significantly reduced.
A number of randomized, double-blind, placebo-controlled trials observed the risks of folic acid and antioxidant vitamins in preventing gastric precancerous lesions, but the results were inconsistent. A multicenter, randomized, double-blind, placebo-controlled clinical trial of 216 CAG patients in China , who were followed up for 6 to 7 years, showed that folic acid combined with vitamin B12 ( 20 mg/day of folic acid, 1 mg per month of an intramuscular injection of vitamin B12, reduced to 2 days per week and 1 intramuscular injection every 3 months, respectively, in the following year) could reverse gastric mucosal atrophy, partially reverse IM, and even significantly reverse dysplasia at one year. Correa et al. al  found that β-carotene (30 mg/day) and vitamin C (1 g/day) could increase the reversal of gastric precancerous lesions (RR = 5.1, 95% CI 1.7–15.0 and RR = 5.0, 95% CI 1.7–14.4) in the groups at high-risk of gastric cancer. Other studies [213, 214] have not found that antioxidant vitamins have a protective effect on gastric precancerous lesions. Some scholars  suggest that effective intervention measures should aim at nutritional supplementation (i.e., a physiological dose rather than a pharmacological dose) in groups at high-risk of gastric cancer. Of course, it is also possible that the intervention and follow-up time in these studies were too short. In addition, the dosage, course of treatment, starting age and the presence or absence of interference from other factors (such as nutritional status) are very important.
Statement 41. The combination of antioxidant vitamins and H. pylori eradication therapy can delay or even block the occurrence and progression of gastric precancerous lesions, thereby reducing the risk of cancer
In the population at high-risk of gastric cancer, antioxidant vitamins combined with H. pylori eradication can block the progression of PLGC. Two domestic clinical intervention trials for CAG patients showed that eradication of H. pylori combined with folic acid could significantly improve the degree of gastric mucosal atrophy, IM and dysplasia [216, 217]. A meta-analysis including two large-scale and long-term RCTs  at home and abroad shows that if gastric precancerous lesions already existed before H. pylori treatment, H. pylori eradication combined with antioxidant vitamins could significantly reduce the relative risk of gastric cancer (RR = 0.5, 95% CI: 0.3–0.9).
Treatment by integrated traditional Chinese and Western medicine
Statement 42. Traditional Chinese medicine has certain efficacy in treating gastric precancerous lesions, and integrated traditional and western medicine has advantages
A meta-analysis showed that Chinese herbal compounds used in the treatment of CAG with dysplasia were superior to Western medications in improving clinical symptoms and had a certain curative effect trend in improving histopathology [218, 219]. The combination of traditional Chinese medicine and Western medicine had advantages in the treatment of gastric precancerous lesions [220,221,222]. A study based on gastric mucosa marking targeting biopsy technology to evaluate the efficacy showed that Moluodan  could improve the clinical symptoms and gastric mucosal pathological status of patients with CAG with dysplasia. This study was cited by the Chinese consensus on chronic gastritis in 2017  and the European guideline for the management of epithelial precancerous conditions and lesions in the stomach in 2019 . In general, there is still a lack of evidence from multicenter, large sample, placebo-controlled, long-term follow-up clinical studies.
The quality of PLGC clinical evaluation studies needs to be improved. These methods will help improve the quality of clinical research to generate more high-level evidence for clinical application, such as scientific positioning, rigorous designs, standardized evaluation methods and research reports.
Statement 43. Strict research designs, procedure quality control, and standardized report are important prerequisites for improving the level of evidence in intervention studies for gastric precancerous lesions
A RCT is a standard design scheme for verifying the efficacy of interventions, and the quality of its research and reports directly affects the judgment of the efficacy of an intervention . In recent years, an increasing number of studies on gastric precancerous diseases and PLGC have been carried out, but the quality of research is still low, which has affected the quality of the evidence . The design of RCT clinical methods should be strengthened, such as random methods, allocation plan hiding, sample size estimation, blind methods, and curative effect evaluation methods . In addition, the research report should be standardized in accordance with the items required by the CONSORT statement .
Statement 44. The clinical intervention research process of precancerous lesions of gastric cancer should generally not be less than 6 months, followed by no less than 6 months of follow-up
The symptoms of CAG and PLGC are recurrent, and the lesions under gastroscopic pathology also show focal and gradual migration changes. It takes 1 to 3 months to regenerate and rebuild the gastric mucosa and restore normal functions. Therefore, the course of CAG treatment should not be less than 3 months (generally 3 to 6 months) . The intervention course for PLGC should be at least 6 months, followed by no less than 6 months of follow-up. Long-term follow-up should be strengthened to observe the end-point indicators, such as the incidence of gastric cancer and the monitoring of disease recurrence.
Positioning and goals of medical interventions
Statement 45. The intervention of chronic atrophic gastritis should be aimed at gastric body or total gastric atrophy and/or intestinal metaplasia to promote the regression of the disease and reduce the risk of gastric cancer. Medical interventions for gastric precancerous lesions should target uncertain dysplasia and low-grade dysplasia, with the goal of promoting the reversal of the disease
Gastric mucosal atrophy, IM and LGD are independent risk factors for gastric cancer. LGD is considered a direct PLGC. Diagnostic ESD resection is recommended for LGD with endoscopic visible lesions and a clear range, while LGD with endoscopic invisible lesions is still an important objective of medical interventions. The wider the range of gastric mucosal atrophy/IM, the higher the risk of gastric cancer . Severe atrophy involving the whole stomach (whether or not it is IM) has a high risk of gastric cancer. Active monitoring and interventions are needed to reduce the risk of gastric cancer.
IFND should not be considered a harmless diagnosis. It is suggested that IFND diagnosed by nontargeted biopsy should be reassessed by gastrointestinal pathologists and reexamined by high-definition endoscopy. It is recommended to perform a second endoscopy after 6–12 months if no lesions are found; it is necessary to develop a monitoring plan based on the severity of the precancerous state and the staging of the lesion range, paying special attention to OLGA stage III/IV patients if repeat nontargeted invisible lesions were found in the biopsy, and no dysplasia was found . Follow-up monitoring can be combined with medical drug interventions.
Statement 46. The efficacy of the evaluation of dysplasia needs to be accurate and to be focused. Targeted monitoring based on MTB technology can help to improve the consistency of biopsy sites before and after treatment
Gastric mucosal atrophy and dysplasia are distributed locally, and the lesions are generally small and hidden. Under white light endoscopy, they usually lack characteristic manifestations. Even if the area is indicated for the first time, it is difficult to accurately clamp at the same part during reexamination. High-definition staining endoscopy and magnifying endoscopy can improve the contrast between the lesion and normal tissue, allow for its histological characteristics to be judged according to the morphological changes of the mucosal microvessels and mucosal glandular duct openings, accurately guide the biopsy and improve the diagnostic rate. The MAPS II guidelines proposed that biopsy assisted by high-definition staining endoscopy is the best method to detect the precancerous state or precancerous lesions of gastric cancer. Mucosal calibration biopsy helps to solve the technical problem of the accurate location of lesions in follow-up monitoring and efficacy evaluations .
Efficacy evaluation methods
Statement 47. The efficacy of the evaluation of gastric precancerous lesions should be based on histopathology, supplemented by a comprehensive evaluation of gastroscopy, symptoms, and quality of life
The impact of PLGC on patients is multifaceted, including organic changes in gastroscopy and histopathology, as well as physical pain and discomfort, psychological anxiety and panic, and a decline in work abilities and social participation abilities, eventually leading to a decline in the quality of life. Therefore, the evaluation of the curative effect for PLGC is mainly based on histopathology, supplemented by a comprehensive evaluation of gastroscopy, symptoms, TCM syndromes, quality of life, psychological evaluations and so on .
Histological semiquantitative evaluation of dysplasia
The histological evaluation of dysplasia is mainly based on qualitative evaluations and can also be evaluated by combination with histological semiquantitative methods.
Statement 48. The histological semiquantitative evaluation of gastric mucosal dysplasia can be carried out from the microscopic level of cell structure atypia and gland disorders to refine the efficacy evaluation research.
Some scholars have used histological semiquantitative methods to diagnose PLGC, including histological atypicality (glandular crowding, irregular glands, intraepithelial folding, deep gland expansion) and cytological atypicality (nuclear polar image, nuclear stratification, nuclear shape and pleomorphism, nuclear ratio, chromatin, nucleolus, etc.) . The semiquantitative evaluation method of dysplasia histology can intuitively display the morphological differences of dysplasia between samples so that it can be more sensitive to the treatment effect and can be explored for clinical research evaluation.
In China, this is the first integrated Chinese and Western medicine clinical management guide on PLGC. It has formulated detailed recommendations for the definition and epidemiology, diagnosis and staging, treatment, monitoring and follow-up of PLGC. A brief flow chart is shown in Fig. 1. Although this guide still has certain limitations, such as some recommendations lacking strong supporting clinical evidence, especially the lack of high-quality domestic research results, it still has clinical guiding significance. This guideline will play an important role in improving the standardization of the clinical diagnosis and treatment of PLGC and the quality of research.
Availability of data and materials
The datasets in this study are available from the corresponding author on reasonable request.
Precancerous lesions of gastric cancer
- H. pylori :
- MAPS II:
Management of epithelial precancerous conditions and lesions in the stomach
Traditional Chinese Medicine
Grading of Recommendations Assessment, Development and Evaluation
World Health Organization
Chronic atrophic gastritis
Gastric epithelial neoplasia
Low-grade intraepithelial neoplasia
High-grade intraepithelial neoplasia
Randomized clinical trial
High-definition white-light endoscopy
Linked color imaging
Blue laser imaging
Regularly arranged collecting venules
European Society of Gastrointestinal Endoscopy
British Society of Gastroenterology (BSG)
Marking targeting biopsy
Endoscopic submucosal dissection
Operative Link on Gastritis Assessment
Operative link on gastric intestinal metaplasia
Endoscopic mucosal resection
Chen H, Zheng R, Le W, et al. Advances in cancer epidemiology in China in 2019. Chin J Dis Control. 2020;24:373–9.
Sun K, Zheng R, Zhang S, et al. Report of cancer incidence and mortality in different areas of China, 2015. Chin Oncol. 2019;28:1–11.
Wang J, Yang Y, Geng Y, et al. Trend analysis of incidence, morbidity and mortality of gastric cancer in China 1990–2017. Chron Dis Prev Control Chin. 2020;28:321–32.
Correa P. Human gastric carcinogenesis: a multistep and multifactorial process–first American cancer society award lecture on cancer epidemiology and prevention. Cancer Res. 1992;52(24):6735–40.
Pimentel-Nunes P, Libânio D, Marcos-Pinto R, et al. Management of epithelial precancerous conditions and lesions in the stomach (MAPS II): European society of gastrointestinal endoscopy (ESGE), European helicobacter and microbiota study group (EHMSG), European society of pathology (ESP), and Sociedade Portuguesa de Endoscopia Digestiva (SPED) guideline update 2019. Endoscopy. 2019;51(4):365–88.
National digestive disease clinical research center (Shanghai) , National Association of Digestive Tract early cancer prevention and treatment centers, Helicobacter pylori, et al. Chinese consensus on management of gastric epithelial precancerous conditions and lesions (2020). J Chin Dig, 2020;40(11) : 731–741
Society of Gastroenterology, Chinese Medical Association. Consensus opinion on chronic gastritis in China (Shanghai, 2017). Chin J Gastroenterol. 2017;22:670–87.
Standardized diagnosis and treatment of gastric low-grade intraepithelial neoplasia, division of gastroendoscopy, Beijing Medical Association (2019). Chinese Journal of Gastrointestinal Endoscopy(Electronic Edition), 2019;6: 49–55.
Society of Spleen and stomach diseases. Chinese academy of traditional Chinese medicine. Consensus on clinical application of gastric mucosa biopsy (2018). Chin J Integr Tradit West Med. 2018;38:1496–9.
Society of Spleen and stomach diseases. Chinese Academy of Traditional Chinese medicine. Consensus opinion of TCM experts on chronic gastritis (2017). Chin J Tradit Chin Med Pharm. 2017;7:3060–4.
Nagayo T. Histological diagnosis of biopsied gastric mucosae with special reference to that of borderline lesion. Gann Monogr. 1971;11:245–56.
Serck-Hanssen A. Precancerous lesions of the stomach. Scand J Gastroenterol Suppl. 1979;54:104–5.
Fenoglio-Preiser C, Carneiro F, Correa P, et al. Gastric Carcinoma. In: Hamilton SR, Aaltonen LA, editors., et al., World Health Organization classification of tumours: pathology and genetics of tumours of the digastive system. Lyon: IARC Press; 2000. p. 37–52.
Ning H. Yu J/WHO (2010) histological classification of digestive system tumors. J Diag Pathol. 2011;18:77–9.
WHO Classification of Tumours Editorial Board. WHO classification of tumours of digestive system[M]. Lyon: IARC Press; 2019.
Du Y, Bai Y, Xie P, et al. Chronic gastritis in China: a national multi-center survey. BMC Gastroenterol. 2014;7:14–21.
Zhang H, Xue Y, Zhou L, et al. Evolution of major upper gastrointestinal diseases and Helicobacter pylori infections over a 35 year grade III, class A hospital in Beijing. Chinese Journal of Internal Medicine. 2016;55:6.
Sipponen P, Maaroos HI. Chronic gastritis. Scand J Gastroenterol. 2015;50(6):657–67.
Park YH, Kim N. Review of atrophic gastritis and intestinal metaplasia as a premalignant lesion of gastric cancer. J Cancer Prev. 2015;20:25–40.
Weck MN, Brenner H. Prevalence of chronic atrophic gastritis in different parts of the world. Cancer Epidemiol Biomarkers Prev. 2006;15(6):1083–94.
Adamu MA, Weck MN, Gao L, et al. Incidence of chronic atrophic gastritis: systematic review and meta-analysis of follow-up studies. Eur J Epidemiol. 2010;25:439–48.
Gao L, Weck MN, Raum E, et al. Helicobacter pylori infection and chronic atrophic gastritis: a population-based study among 9444 older adults from Germany. Int J Epidemiol. 2010;39:129–34.
Yeh LY, Raj M, Hassan S, et al. Chronic atrophic antral gastritis and risk of metaplasia and dysplasia in an area with low prevalence of Helicobacter pylori. Indian J Gastroenterol. 2009;28:49–52.
Nguyen TL, Uchida T, Tsukamoto Y, et al. Helicobacter pylori infection and gastroduodenal diseases in Vietnam: a cross-sectional, hospital-based study. BMC Gastroenterol. 2010;10:114.
Shen H. Treatment of chronic Atrophic gastritis and precancerous lesions. Jiangsu Tradit Chin Med. 2007;8:6–7.
Shi S, Lu W. Professor Shan Zhaowei’s experience in treating chronic Atrophic gastritis precancerous lesions. Educ Tradit Chin Med. 1998;17(4):44–46.
Hu L, Ma J. Prof Lo Siu-yin’s experience in differentiation and treatment of precancerous gastric cancer. New Chin Med. 2006;38(5):7–9.
Su Z, Zhang W, Zhang Y, et al. Chronic gastritis malignant transformation process syndrome, syndrome element evolution law. Mod Chin Med Clin. 2017;6:9–14.
Su Z, Li P, Guo Q, et al. Study on the law of TCM syndrome evolution of chronic gastritis. J Beijing Univ Chin Med. 2015;11(762–766):771.
Cheng R, Cui Y, Chen L, et al. Study on regularity of TCM syndrome types of chronic Atrophic gastritis precancerous lesions based on logistic regression model. Chin J Tradit Chin Med. 2018;33(8):3623–6.
Chao J, Zhen X, Liu S. Study on the evolution of TCM syndromes of chronic Atrophic gastritis. Beijing Tradit Chin Med. 2019;1:48–50.
Yao K, Naghama T, Matsui T, et al. Detection and characterization of early gastric cancer for curative endoscopic submucosal dissection. Dig Endosc. 2013;25:44–54.
Kenshi Y, Noriya U, Tomoari K, et al. (JGES Guidelines) Guidelines for Endoscopic Diagnosis of Early Gastric Cancer. Dig Endosc. 2020;32(5):663–98.
Bertoni G, Gumina C, Conigliaro R, et al. Randomized placebo-controlled trial of oral liquid simethicone prior to upper gastrointestinal endoscopy. Endoscopy. 1992;24:268–70.
Lee GJ, Park SJ, Kim SJ, et al. Effectiveness of premedication with pronase for visualization of the mucosa during endoscopy: a randomized, controlled trial. Clin Endosc. 2012;45:161–4.
Lee SY, Han HS, Cha JM, et al. Endoscopic flushing with pronase improves the quantity and quality of gastric biopsy: a prospective study. Endoscopy. 2014;46:747–53.
Kim GH, Cho YK, Cha JM, et al. Effect of pronase as mucolytic agent on imaging quality of magnifying endoscopy. World J Gastroenterol. 2015;21:2483–9.
Chen X, Chu G, Lu C, et al. Value of combination of dimethylsiloxane powder and chymotrypsin in gastroscopy [J ]. Chongqing Med. 2018;47(20):2744–6.
Liu X, Guan CT, Xue LY, et al. Effect of premedication on lesion detection rate and visualization of the mucosa during upper gastrointestinal endoscopy: a multicenter large sample randomized controlled double-blind study. Surg Endosc. 2018;32(8):3548–56.
Yao K. The endoscopic diagnosis of early gastric cancer. Ann Gastroenterol. 2013;26:11–22.
Hiki N, Kurosaka H, Tatsutomi Y, et al. Peppermint oil reduces gastric spasm during upper endoscopy: a randomized, double-blind, double-dummy controlled trial. Gastrointest Endosc. 2003;57:475–82.
Cohen LB, Delegge MH, Aisenberg J, et al. AGA Institute review of endoscopic sedation. Gastroenterology. 2007;133(2):675–701.
Obara K, Haruma K, Irisawa A, et al. Guidelines for sedation in gastroenterological endoscopy. Digest Endosc. 2015;27:435–49.
Probert CS, Jayanthi V, Quinn J, et al. Information requirements and sedation preferences of patients undergoing endoscopy of the upper gastrointestinal tract. Endoscopy. 1991;23(4):218–9.
Gastroenterologist branch of Chinese Medical Doctor Association.painless endoscopy. Chinese Journal of Practical Internal Medicine. 2010; 30(7): 605–607.
Panteris V, Nikolopoulou S, Lountou A, et al. Diagnostic capabilities of high-definition white light endoscopy for the diagnosis of gastric intestinal metaplasia and correlation with histologic and clinical data. Eur J Gastroenterol Hepatol. 2014;26:594–601.
Pimentel-Nunes P, Libanio D, Lage J, et al. A multicenter prospective study of the real-time use of narrow-band imaging in the diagnosis of premalignant gastric conditions and lesions. Endoscopy. 2016;48:723–30.
Zhao Z, Yin Z, Wang S, et al. Meta-analysis: the diagnostic efficacy of chromoendoscopy for early gastric cancer and premalignant gastric lesions. J Gastroenterol Hepatol. 2016;31(9):1539–45.
Kikuste I, Marques-Pereira R, Monteiro-Soares M, et al. Systematic review of the diagnosis of gastric premalignant conditions and neoplasia with high-resolution endoscopic technologies. Scand J Gastroenterol. 2013;48:1108–17.
Ang TL, Pittayanon R, Lau JY, et al. A multicenter randomized comparison between high-definition white light endoscopy and narrow band imaging for detection of gastric lesions. Eur J Gastroenterol Hepatol. 2015;27:1473–8.
Dutta AK, Sajith KG, Pulimood AB, et al. Narrow band imaging versus white light gastroscopy in detecting potentially premalignant gastric lesions: a randomized prospective crossover study. Indian J Gastroenterol. 2013;32:37–42.
Le FW, Wang XS, Yin W. Value of electronic staining combined with indigo carmine staining in the diagnosis of early gastric cancer and precancerous lesions. Gansu Med. 2017;36:44–5.
Zhang LiY. Application of NBI combined with acetic acid and methylene blue staining in early gastric cancer and precancerous lesions. Fujian Med J. 2018;40:38–40.
Zhang Y, Zhang L, Liang YY. Endoscopic acetic acid staining combined with narrow band light imaging in the diagnosis of early gastric cancer and precancerous lesions. Clin Med. 2019;39:49–50.
Kentaro S, Jan T, Ernst JK, et al. Kyoto global consensus report on Helicobacter pylori gastritis. Gut. 2015;64(9):1353–67.
Banks M, Graham D, Jansen M, et al. British society of gastroenterology guidelines on the diagnosis and management of patients at risk of gastric adenocarcinoma. Gut. 2019;68(9):1545–75.
Division of pathology. Chinese society of digestive endoscopy, Chinese society of digestive endoscopy, expert consensus (Draft). Chinese Journal of Digestion. 2014;34(9):577–81.
Preparatory group of digestive pathology group, Pathology branch, Chinese Medical Association. Consensus of pathological diagnosis of gastric mucosa biopsy in chronic gastritis and epithelial tumor. Chin J Pathol. 2017;46(5):289–93.
Lash JG, Genta RM. Adherence to the Sydney system guidelines increases the detection of Helicobacter gastritis and intestinal metaplasia in 400738 sets of gastric biopsies. Aliment Pharmacol Ther. 2013;38:424–31.
Kwack WG, Ho WJ, Kim JH, et al. Understanding the diagnostic yield of current endoscopic biopsy for gastric neoplasm: a prospective single-center analysis based on tumor characteristics stratified by biopsy number and site. Medicine. 2016;95: e41967.
Januszewicz W, Wieszczy P, Bialek A, et al. Endoscopist biopsy rate as a quality indicator for outpatient gastroscopy: a multicenter cohort study with validation. GastrointestEndosc. 2019;89:1141–9.
Sun LM, Si JM, Chen SJ, et al. The setablishment and clinical appliance of technique of mucosa marking targeting biopsy. Hepatogastroenterology. 2009;56(89):59–62.
Sun LM, Si JM, Fan YJ. Experimental study on one-step endoscopic calibration biopsy. J Chin Dig. 2006;26:488–9.
Liu HY, Chen YC, Qing P, et al. The effect of Banxia xiexin decoction on chronic Atrophic gastritis was evaluated by standard biopsy technique. Chin Arch Tradit Chin Med. 2014;32:804–7.
Society of Digestive diseases, Chinese medical association. Consensus on chronic gastritis in China (2012). Chin J Dig Endosc. 2013;18(1):24–36.
Wu YQ, Lin Q, Sun X, et al. The value of scaling biopsy in follow-up of gastric mucosal lesion. Chin J Dig Endosc. 2016;33:551–3.
Kim CG. Tissue acquisition in gastric epithelial tumor prior to endoscopic resection. Clin Endosc. 2013;46(5):436–40.
Graham DY, Schwartz JT, Cain GD, et al. Prospective evaluation of biopsy number in the diagnosis of esophageal and gastric carcinoma. Gastroenterology. 1982;82(2):228–31.
Society of gastroendoscopy, Chinese Medical Association, Professional committee of Tumor Endoscopy, Chinese anti-cancer association. Consensus opinion on early gastric cancer screening and endoscopy in China (Changsha, 2014). Chin J Dig Endosc. 2014;31:361–77.
Wakita S, Takemura K, Minato H, et al. Optimal number of endoscopic biopsies for diagnosis of early gastric cancer. Endosc Int Open. 2019;7(12):E1683-1690.
Yao K, Doyama H, Gotoda T, et al. Diagnostic performance and limitations of magnifying narrow-band imaging in screening endoscopy of early gastric cancer: a prospective multicenter feasibility study. Gastric Cancer. 2014;17(4):669–79.
Chiu PWY, Uedo N, Singh R, et al. An Asian consensus on standards of diagnostic upper endoscopy for neoplasia. Gut. 2019;68(2):186–97.
Koyama H-N. Methods and strategies for endoscopic diagnosis of early gastric cancer. 2017;1:29–32.
Filipe MI, Muñoz N, Matko I, et al. Intestinal metaplasia types and the risk of gastric cancer: a cohort study in Slovenia. Int J Cancer. 1994;57:324–9.
Conchillo JM, Houben G, de Bruïne A, et al. Is type III intestinal metaplasia an obligatory precancerous lesion in intestinal-type gastric carcinoma? Eur J Cancer Prev. 2001;10:307–312.
Piazuelo MB, Camargo MC, Mera RM, et al. Gastric intestinal metaplasia type III and prospective risk of gastric cancer in colombia. Gastroenterology. 2017;152:S473.
Shah SC, Gawron AJ, Mustafa R, et al. Histologic subtyping of gastric intestinal metaplasia: overview and considerations for clinical practice. Gastroenterology. 2020;158(3):745–750.
Bolscher J, Sobrinho SIMESM. Mucins as key molecules for the classification of intestinal metaplasia of the stomach. Virchows Arch. 2002;440:311–7.
Duan XJ, Lian HW, Li J, et al. Expression of GCRG213p, LINE-1 endonuclease variant, significantly different in gastric complete and incomplete intestinal metaplasia. Diagn Pathol. 2019;14:61.
Dong B, Xie Y-Q, KeChen, et al. Differences in biological features of gastric dysplasia, indefinite dysplasia, reactive hyperplasia and discriminant analysis of these lesions. World J Gastroenterol. 2005;11(23):3595–600.
Baldus SE, Monig SP, Arkenau V, et al. Correlation of MUC5AC immunoreactivity with histopathological subtypes and prognosis of gastric carcinoma. Ann Surg Oncol. 2002;9:887–93.
Simone A, Casadei A, De Vergori E, et al. Rescue endoscopy to identify site of gastric dysplasia or carcinoma found at random biopsies. Dig Liver Dis. 2011;43(9):721–5.
De Vries AC, van Grieken NC, Looman CW, et al. Gastric cancer risk in patients with premalignant gastric lesions: a nationwide cohort study in the Netherlands. Gastroenterology. 2008;134(4):945–52.
Akbari M, Kardeh B, Tabrizi R, et al. Incidence rate of gastric cancer adenocarcinoma in patients with gastric dysplasia: a systematic review and meta-analysis. J Clin Gastroenterol. 2019;53(10):703–10.
Lim H, Jung HY, Park YS, et al. Discrepancy between endoscopic forceps biopsy and endoscopic resection in gastric epithelial neoplasia. Surg Endosc. 2014;28(4):1256–62.
Zhao G, Xue M, Hu Y, et al. How commonly is the diagnosis of gastric low grade dysplasia upgraded following endoscopic resection? A meta-analysis. PLoS ONE. 2015;10(7):e0132699.
Wu B, Ling HEQ, Yang J, et al. Clinical pathology and prognosis of low grade intraepithelial neoplasia of gastric mucosa. J Mil Med Cont Edu Coll. 2011;32(6):598–600.
Goo JJ, Choi CW, Kang DH, et al. Risk factors associated with diagnostic discrepancy of gastric indefinite neoplasia: who need en bloc resection? Surg Endosc. 2015;29(12):3761–7.
Raftopoulos SC, Kumarasinghe P, de Boer B, et al. Gastric intraepithelial neoplasia in a Western population. Eur J Gastroenterol Hepatol. 2012;24(1):48–54.
Fassan M, Pizzi M, Farinati F, et al. Lesions indefinite for intraepithelial neoplasia and OLGA staging for gastric atrophy. Am J Clin Pathol. 2012;137(5):727–32.
Rugge M, Farinati F, Baffa R, et al. Gastric epithelial dysplasia in the natural history of gastric cancer: a multicenter prospective follow-up study. Interdisciplinary group on gastric epithelial dysplasia. Gastroenterology. 1994;107(5):1288–96.
Rugge M, Cassaro M, Di Mario F, et al. Interdisciplinary Group on Gastric Epithelial Dysplasia (IGGED). The long term outcome of gastric non-invasive neoplasia. J Gut. 2003;52(8):1111–6.
Kapadia CR. Gastric atrophy, metaplasia, and dysplasia: a clinical perspective. J Clin Gastroenterol. 2003;36(5 Suppl):S29-36.
Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. an attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 1965;64:31–49.
Fukao A, Hisamichi S, Ohsato N, et al. Correlation between the prevalence of gastritis and gastric cancer in Japan. Cancer Causes Control. 1993;4(1):17–20.
Genta RM. Review article: gastric atrophy and atrophic gastritis–nebulous concepts in search of a definition. Aliment Pharmacol Ther. 1998;12(Suppl 1):17–23.
Shichijo S, Hirata Y, Niikura R, et al. Histologic intestinal metaplasia and endoscopic atrophy are predictors of gastric cancer development after Helicobacter pylori eradication. Gastrointest Endosc. 2016;84(4):618–24.
Lahner E, Esposito G, Pilozzi E, et al. Occurrence of gastric cancer and carcinoids in atrophic gastritis during prospective long-term follow up. Scand J Gastroenterol. 2015;50(7):856–65.
Reddy KM, Chang JI, Shi JM, et al. Risk of gastric cancer among patients with intestinal metaplasia of the stomach in a US integrated health care system. Clin Gastroenterol Hepatol. 2016;14(10):1420–5.
Zhou Y, Li HY, Zhang JJ, et al. Operative link on gastritis assessment stage is an appropriate predictor of early gastric cancer. World J Gastroenterol. 2016;22(13):3670–8.
Kodama M, Murakami K, Okimoto T, et al. Histological characteristics of gastric mucosa prior to Helicobacter pylori eradication may predict gastric cancer. Scand J Gastroenterol. 2013;48(11):1249–56.
Oliveira C, Pinheiro H, Figueiredo J, Seruca R, Carneiro F. Familial gastric cancer: genetic susceptibility, pathology, and implications for management. Lancet Oncol. 2015;16(2):e60-70.
Yaghoobi M, Bijarchi R, Narod SA. Family history and the risk of gastric cancer. Br J Cancer. 2010;102(2):237–42.
Safaee A, Moghimi-Dehkordi B, Fatemi SR, et al. Family history of cancer and risk of gastric cancer in Iran. Asian Pac J Cancer Prev. 2011;12(11):3117–20.
Masuyama H, Yoshitake N, Sasai T, et al. Relationship between the degree of endoscopic atrophy of the gastric mucosa and carcinogenic risk. Digestion. 2015;91(1):30–6.
Kuipers EJ. Pernicious anemia, atrophic gastritis, and the risk of cancer. Clin Gastroenterol Hepatol. 2015;13(13):2290–2.
Murphy G, Dawsey SM, Engels EA, et al. Cancer risk after pernicious anemia in the US elderly population. Clin Gastroenterol Hepatol. 2015;13(13):2282-2289e4.
Ye W, Nyren O. Risk of cancers of the oesophagus and stomach by histology or subsite in patients hospitalised for pernicious anaemia. Gut. 2003;52(7):938–41.
Vannella L, Lahner E, Osborn J, Annibale B. Systematic review: gastric cancer incidence in pernicious anaemia. Aliment Pharmacol Ther. 2013;37(4):375–82.
Hsing AW, Hansson LE, McLaughlin JK, et al. Pernicious anemia and subsequent cancer A population-based cohort study. Cancer. 1993;71(3):745–50.
Brinton LA, Gridley G, Hrubec Z, et al. Cancer risk following pernicious anaemia. Br J Cancer. 1989;59(5):810–3.
Sjoblom SM, Sipponen P, Jarvinen H. Gastroscopic follow up of pernicious anaemia patients. Gut. 1993;34(1):28–32.
Armbrecht U, Stockbrugger RW, Rode J, et al. Development of gastric dysplasia in pernicious anaemia: a clinical and endoscopic follow up study of 80 patients. Gut. 1990;31(10):1105.
Lahner E, Caruana P, D’Ambra G, et al. First endoscopic-histologic follow-up in patients with body-predominant atrophic gastritis: when should it be done? Gastrointest Endosc. 2001;53(4):443–8.
Cai Q, Zhu C, Yuan Y, et al. Development and validation of a prediction rule for estimating gastric cancer risk in the Chinese high-risk population: a nationwide multicentre study. Gut. 2019;68(9):1576–87.
Zagari RM, Rabitti S, Greenwood DC, et al. Systematic review with meta-analysis: diagnostic performance of the combination of pepsinogen, gastrin-17 and anti-Helicobacter pylori antibodies serum assays for the diagnosis of atrophic gastritis. Aliment Pharmacol Ther. 2017;46(7):657–67.
Syrjanen K. A panel of serum biomarkers (gastropanel(R)) in non-invasive diagnosis of atrophic gastritis systematic review and meta-analysis. Anticancer Res. 2016;36(10):5133–44.
Chen Z, Hong L, Liu L, et al. Monoclonal antibody MG7 as a screening tool for gastric cancer. Hybridoma. 2010;29(1):27–30.
Zhang L, Ren J, Pan K, et al. Detection of gastric carcinoma-associated MG7-Ag by serum immuno-PCR assay in a high-risk Chinese population, with implication for screening. Int J Cancer. 2010;126(2):469–73.
Guo DL, Dong M, Wang L, et al. Expression of gastric cancer-associated MG7 antigen in gastric cancer, precancerous lesions and H. pylori -associated gastric diseases. World J Gastroenterol. 2002;8(6):1009–13.
Jiang J, Shen S, Dong N, et al. Correlation between negative expression of pepsinogen C and a series of phenotypic markers of gastric cancer in different gastric diseases. Cancer Med. 2018;7(8):4068–76.
Yang Zhenhua SB, Huang AS, et al. Gastroscopic and pathological features of chronic atrophic gastritis syndrome. Chin J Integr Chin West Med Dig. 2021;29(1):58–61.
Song J, Yuan MH, Liu ZH, et al. Association of serum pepsin levels with high risk syndromes of gastric precancerous lesions. Lishizhen Med Mater Med Res. 2020;31(7):1658–60.
Yang Y, Qu XH, Yang M, et al. Association between TCM syndromes and cancer risk in chronic Atrophic gastritis patients. J Tradit Chin Med. 2020;61(4):319–24.
Wang P, Shi B, Wen YD, Tang XD. Study on the establishment of risk prediction model for combination of syndrome and disease in gastric precancerous lesions. Chin J Integr Tradit West Med. 2018;38(7):773–8.
Genta RM, Lew GM, Graham DY. Changes in the gastric mucosa following eradication of Helicobacter pylori. Mod Pathol. 1993;6:281.
Kawai T, Moriyasu F, Tsuchida A. Key issues associated with helicobacter pylori eradication. Digestion. 2016;93:19.
Sung JJ, Lin SR, Ching JY, et al. Atrophy and intestinal metaplasia one year after cure of H. pylori infection: a prospective, randomized study. Gastroenterology. 2000;119:7.
Gong EJ, Kim DH, Ahn JY, et al. Effects of proton pump inhibitor on the distribution of Helicobacter pylori and associated gastritis in patients with gastric atrophy. Digestion. 2019;101:279.
Kitauchi OH, Yoshimura SN, et al. Progression of chronic atrophic gastritis associated with Helicobacter pylori infection increases risk of gastric cancer. IntJ Cancer. 2004;109:138–43.
Yi-Qi DU, Li G, Quan-Cai C, et al. Gastro-protecting effect of gefarnate on chronic erosive gastritis with dyspeptic symptoms. Chin Med J. 2012;125(16):2878–84.
Yun CY, Kim N, Lee J, et al. Usefulness of OLGA and OLGIM system not only for intestinal type but also for diffuse type of gastric cancer, and no interaction among the gastric cancer risk factors. Helicobacter. 2018;23(6):e12542.
Mera RM, Bravo LE, Camargo MC, et al. Dynamics of Helicobacter pylori infection as a determinant of progression of gastric precancerous lesions: 16-year follow-up of an eradication trial. Gut. 2018;67(7):1239–46.
Rugge M, Meggio A, Pravadelli C, et al. Gastritis staging in the endoscopic follow-up for the secondary prevention of gastric cancer: a 5-year prospective study of 1755 patients. Gut. 2019;68(1):11–7.
Yamada H, Ikegami M, Shimoda T, et al. Long-term follow- up study of gastric adenoma/dysplasia. Endoscopy. 2004;36(5):390–6.
Kang DH, Choi CW, Kim HW, et al. Predictors of upstage diagnosis after endoscopic resection of gastric low-grade dysplasia. Surg Endosc. 2018;32(6):2732–8.
Yang L, Jin P, Wang X, et al. Risk factors associated with histological upgrade of gastric low-grade dysplasia on pretreatment biopsy. J Dig Dis. 2018;19(10):596–604.
Min B-H, Kim K-M, Kim ER, et al. Endoscopic and histopathological characteristics suggesting the presence of gastric mucosal high grade neoplasia foci in cases initially diagnosed as gastric mucosal low grade neoplasia by forceps biopsy in Korea. J Gastroenterol. 2011;46(1):17–24.
Svetlana K, Anna B, Oleg R, et al. Stomach-specific biomarkers (GastroPanel) can predict the development of gastric cancer in a caucasian population: a longitudinal nested case-control study in Sibera. Anticancer Res. 2016;36(1):247–53.
Ryu DG, Choi CW, Kang DH, et al. Pathologic outcomes of endoscopic submucosal dissection for gastric epithelial neoplasia. Medicine. 2018;97(33):e11802.
Back MK, et al. Analysis of factors associated with local recurrence after endoscopic resection of gastric epithelial dysplasia: a retrospective study. BMC Gastroenterol. 2020;20(1):148.
Kwon MJ, Kang HS, Kim HT, et al. Treatment for gastric ‘indefinite for neoplasm/dysplasia’ lesions based on predictive factors. World J Gastroenterol. 2019;25(4):469–84.
Lee H, Kim H, Shin SK, et al. The Diagnostic role of endoscopic submucosal dissection for gastric lesions with indefinite pathology. Scand J Gastroenterol. 2012;47(8–9):1101–7.
Yu CH, Jeon SW, Kim SK, et al. Endoscopic resection as a first therapy for gastric epithelial atypia: is it reasonable? Dig Dis Sci. 2014;59(12):3012–20.
Beijing Science and Technology Commission Major Project “early gastric cancer treatment standard research” expert group. Expert consensus opinion on endoscopic standardized resection of early gastric cancer. Chin J Gastroenterol. 2018(2): 49–60.
Yuan JX. Endoscopic high-frequency electrocoagulation combined with Kangfuxin solution in the treatment of 32 gastrointestinal polyps. Guide Chin Med. 2008;15:144–5.
Wen YP, Peng FY. Effect of kangfuxin solution on upper gastrointestinal polyp after electrotomy. Hainan Med. 2012;23(1):70–1.
Wang HG, Wang Y, Guo QM. Kangfuxinye combined with pantoprazole in the treatment of gastric ulcer after gastrectomy. Chin J Integr Tradit West Med. 2013;21(7):382–3.
Tang SB, Wang ML, Liang J, et al. Therapeutic effect of Jianweiyuyang tablet on precancerous lesion of stomach. J Mod Integr Chin West Med. 2009;18(30):3678–9.
Wang CX, Wang QM, Song LW, et al. Jianweiyuyang tablets for the repair of iatrogenic ulcers after endoscopic surgery. Chin Med Innov. 2015;12(7):22–4.
Wenzhong L, Yong X, Hong L, Hong C, Zhirong Z, Liya Z, Ye C, Jiangbin W, Yiqi D, Nonghua Lv. Fifth national consensus report on the management of helicobacter pylori infection. Chin J Int Med. 2017;56(7):532–45.
Xia ZW, Jiang GD. Experimental observation on anti-typhoid bacilli activity and in vitro compatibility of antibacterial drugs of gegenqinlian decoction. J Integr Chin West Med. 1996;9(7):394.
Li T. A survey of research on prevention and treatment of bacterial resistance with traditional Chinese medicine. Chin J Med. 2001;16(3):29.
Shi JB. Observation on the therapeutic effect of integrated traditional Chinese and western medicine on Helicobacter pylori patients. J Mod Integr Chin West Med. 2003;12(7):721.
Hua ZM, Ma ZQ, Tong BL, et al. Helicobacter pylori therapy in combination with traditional Chinese medicine. Chin J Tradit Chin West Med. 2008;9(2):115–8.
Shen XH, Cui ML. Progress in the treatment of drug resistant Helicobacter pylori with traditional Chinese and Western medicine. Fujian Med J. 2008;30(4):91–3.
Wang ML, Liu JH, Mao LF, et al. Advance in diagnosis and treatment of gastric precancerous lesions. J Clin Chin Med. 2020;32(1):171–4.
Jiang N, Huang X, Fan YH, et al. Systematic review of integrated traditional and western medicine in the treatment of gastric precancerous lesions. Chin J Tradit Chin Med. 2015;33(1):149–54.
Lundell L, Miettinen P, Myrvold HE, et al. Lack of effect of acid suppression therapy on gastric atrophy. Nordic Gerd Study Group Gastroenterol. 1999;117(2):319–26.
Eslami L, Nasseri-Moghaddam S. Meta-analyses: does long-term PPI use increase the risk of gastric premalignant lesions? Arch Iran Med. 2013;16(8):449–58.
Song H, Zhu J, Lu D. Long-term proton pump inhibitor (PPI) use and the development of gastric pre-malignant lesions. Cochrane Database Syst Rev. 2014. https://doi.org/10.1002/14651858.CD010623.pub2.
Nasser SC, Slim M, Nassif JG, et al. Influence of proton pump inhibitors on gastritis diagnosis and pathologic gastric changes. World J Gastroenterol. 2015;21(15):4599–606.
Niikura R, Hayakawa Y, Hirata Y, et al. The reduction in gastric atrophy after eradication is reduced by treatment with inhibitors of gastric acid secretion. Int J Mol Sci. 2019;20(8):1913.
Seo SI, Park CH, You SC, et al. Association between proton pump inhibitor use and gastric cancer: a population-based cohort study using two different types of nationwide databases in Korea. Gut. 2021;11:gutjnl-2020 323845.
Dias-Neto M, Pintalhao M, Ferreira M, et al. Salt intake and risk of gastric intestinal metaplasia: systematic review and meta-analysis. Nutr Cancer. 2010;62(2):133–47.
Park YM, Kim JH, Baik SJ, et al. Clinical risk assessment for gastric cancer in asymptomatic population after a health check-up: an individualized consideration of the risk factors. Medicine (Baltimore). 2016;95(44):e5351.
Song JH, Kim YS, Heo NJ, et al. High salt intake is associated with atrophic gastritis with intestinal metaplasia. Cancer Epidemiol Biomarkers Prev. 2017;26(7):1133–8.
Thapa S, Fischbach LA, Delongchamp R, et al. Association between dietary salt intake and progression in the gastric precancerous process. Cancers. 2019;11(4):467.
Shikata K, Kiyohara Y, Kubo M, et al. A prospective study of dietary salt intake and gastric cancer incidence in a defined Japanese population: the Hisayama study. Int J Cancer. 2006;119(1):196–201.
Ke L, Zhang D, Chen Y, et al. Investigation on the risk factors of intestinal metaplasia in Northwest China gastric mucosa. Adv Mod Biomed. 2016;16(34):6639–43.
Yu Y, Fang C, Peng C, et al. Risk factors for gastric intraepithelial neoplasia in Chinese adults: a case-control study. Cancer Manag Res. 2018;10:2605–13.
Tan MC, Mallepally N, Liu Y, et al. Demographic and Lifestyle Risk Factors for Gastric Intestinal Metaplasia Among US Veterans. Am J Gastroenterol. 2020;115:3.
Lahner E, Carabotti M, Esposito G, et al. Occurrence and predictors of metaplastic atrophic gastritis in a nation-wide consecutive endoscopic population presenting with upper gastrointestinal symptoms. Eur J Gastroenterol Hepatol. 2018;30(11):1291–6.
You WC, Li JY, Zhang L, Jin ML, et al. Etiology and prevention of gastric cancer: a population study in a high risk area of China. Chin J Dig Dis. 2005;6(4):149–54.
Xing J, Min L, Zhu S, et al. Factors associated with gastric adenocarcinoma and dysplasia in patients with chronic gastritis: a population-based study. Chin J Cancer Res. 2017;29(4):341–50.
Kim K, Chang Y, Ahn J, et al. Smoking and urinary cotinine levels are predictors of increased risk for gastric intestinal metaplasia. Cancer Res. 2019;79(3):676–84.
Peleteiro B, Lunet N, Figueiredo C, et al. Smoking, Helicobacter pylori virulence, and type of intestinal metaplasia in Portuguese males. Cancer Epidemiol Biomarkers Prev. 2007;16(2):322–6.
Kato I, Vivas J, Plummer M, et al. Environmental factors in Helicobacter pylori-related gastric precancerous lesions in Venezuela. Cancer Epidemiol Biomarkers Prev. 2004;13(3):468–76.
Nakamura M, Haruma K, Kamada T, et al. Cigarette smoking promotes atrophic gastritis in Helicobacter pylori-positive subjects. Dig Dis Sci. 2002;47(3):675–81.
Nieminen AA, Kontto J, Puolakkainen P, et al. Long-term gastric cancer risk in male smokers with atrophic corpus gastritis. Scand J Gastroenterol. 2019;54(2):145–51.
Nam JH, Choi IJ, Kook MC, et al. OLGA and OLGIM stage distribution according to age and Helicobacter pylori status in the Korean population. Helicobacter. 2014;19(2):81–9.
Sobala GM, Pignatelli B, Schorah CJ, et al. Levels of nitrite, nitrate, N-nitroso compounds, ascorbic acid and total bile acids in gastric juice of patients with and without precancerous conditions of the stomach. Carcinogenesis. 1991;12(2):193–8.
Sobala GM, O’Connor HJ, et al. Bile reflux and intestinal metaplasia in gastric mucosa. J ClinPathol. 1993;46(3):235–40.
Matsuhisa T, Arakawa T, Watanabe T, et al. Relation between bile acid reflux into the stomach and the risk of atrophic gastritis and intestinal metaplasia: a multicenter study of 2283 cases. Dig Endosc. 2013;25(5):519–25.
Matsuhisa T, Tsukui T. Relation between reflux of bile acids into the stomach and gastric mucosal atrophy, intestinal metaplasia in biopsy specimens. J Clin Biochem Nutr. 2012;50(3):217–21.
Dixon MF, Mapstone NP, Neville PM, et al. Bile reflux gastritis and intestinal metaplasia at the cardia. Gut. 2002;51(3):351–5.
Li D, Zhang J, Yao WZ, et al. The relationship between gastric cancer, its precancerous lesions and bile reflux: a retrospective study. J Dig Dis. 2020;21(4):222–9.
Zhang L, Zhang J, Li D, et al. Bile reflux is an independent risk factor for precancerous gastric lesions and gastric cancer: an observational cross-sectional study. J Dig Dis. 2021;22(5):282–90.
Jiang JX, Liu Q, Zhao B, et al. Risk factors for intestinal metaplasia in a southeastern Chinese population: an analysis of 28,745 cases. J Cancer Res Clin Oncol. 2017;143(3):409–18.
Tang XD, Zhou LY, Zhang ST, et al. Randomized double-blind clinical trial of moluodan for the treatment of chronic atrophic gastritis with dysplasia. Chin J Integr Med. 2016;22(1):9–18.
Wong BC, Lam SK, Wong WM, et al. Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. JAMA. 2004;291(2):187–94.
Ma JL, Zhang L, Brown LM, et al. fifteen-year effects of Helicobacter pylori, garlic, and vitamin treatments on gastric cancer incidence and mortality. J Natl Cancer Inst. 2012;104(6):488–92.
Doorakkers E, Lagergren J, Engstrand L, Brusselaers N. Helicobacter pylori eradication treatment and the risk of gastric adenocarcinoma in a Western population. Gut. 2018;67(12):2092–6.
Leung WK, Wong IOL, Cheung KS, et al. Effects of Helicobacter pylori treatment on incidence of gastric cancer in older individuals. Gastroenterology. 2018;155(1):67–75.
Ford AC, Forman D, Hunt RH, Yuan Y, Moayyedi P. Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomised controlled trials. BMJ. 2014;348:g3174.
Choi IJ, Kim CG, Lee JY, et al. Family history of gastric cancer and Helicobacter pylori treatment. N Engl J Med. 2020;382(5):427–36.
Chen HN, Wang Z, Li X, et al. Helicobacter pylori eradication cannot reduce the risk of gastric cancer in patients with intestinal metaplasia and dysplasia: evidence from a meta-analysis. Gastric Cancer. 2016;19(1):166–75.
Li WQ, Ma JL, Zhang L, et al. Effects of Helicobacter pylori treatment on gastric cancer incidence and mortality in subgroups. J Natl Cancer Inst. 2014;106(7):dju116.
Den Hollander WJ, Holster IL, den Hoed CM, et al. Surveillance of premalignant gastric lesions: a multicentre prospective cohort study from low incidence regions. Gut. 2019;68(4):585–93.
Uemura N, Mukai T, Okamoto S, et al. Effect of Helicobacter pylori eradication on subsequent development of cancer after endoscopic resection of early gastric cancer. Cancer Epidemiol Biomarkers Prev. 1997;6:639–42.
Fukase K, Kato M, Kikuchi S, et al. Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial. Lancet. 2008;372:392–7.
Choi J, Kim SG, Yoon H, et al. Eradication of Helicobacter pylori after endoscopic resection of gastric tumors does not reduce incidence of metachronous gastric carcinoma. Clin Gastroenterol Hepatol. 2014;12(5):791–800.
Choi IJ, Kook MC, Kim YI, et al. Helicobacter pylori therapy for the prevention of metachronous gastric cancer. N Engl J Med. 2018;378:1085–95.
Cheng H, Hu FL, Sheng JQ, et al. Jinghua Weikang capsule combined with triple or quadruple Furazolidone therapy for Helicobacter pylori infection: a multicenter, randomized, controlled study. Chin J Med. 2016;9640:3206–12.
Li JX, Lu B, Du Q, et al. Jinghuaweikang capsule combined with bismuth quadruple in the treatment of Helicobacter pylori chronic gastritis. Chin J Integr Chin Western Med Dig. 2018;26(12):998–1004.
He XM, Huang X. Combination of Weifuchun and quadruple therapy for H. Helicobacter pylori associated chronic Atrophic gastritis. World J Chin Dig. 2017;25(6):521–5.
Lunet N, Lacerda-Vieira A, Barros H. Fruit and vegetables consumption and gastric cancer: a systematic review and meta-analysis of cohort studies. Nutr Cancer. 2005;53(1):1–10.
Kong P, Cai Q, Geng Q, et al. Vitamin intake reduce the risk of gastric cancer: meta-analysis and systematic review of randomized and observational studies. PLoS ONE. 2014;9(12):e116060.
Dawsey SP, Hollenbeck A, Schatzkin A, et al. A prospective study of vitamin and mineral supplement use and the risk of upper gastrointestinal cancers. PLoS ONE. 2014;9(2):e88774.
Li WQ, Zhang JY, Ma JL, et al. Effects of Helicobacter pylori treatment and vitamin and garlic supplementation on gastric cancer incidence and mortality: follow-up of a randomized intervention trial. BMJ. 2019;366:l5016.
Zhu SS, Mason Joel, Shi Y, et al. Effects of folic acid on the development of gastric cancer and other gastrointestinal cancers: a seven-year follow-up study. Chin J Gastroenterol. 2002;7(2):73–8.
Correa P, Fontham ET, Bravo JC, et al. Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-helicobacter pylori therapy. J Natl Cancer Inst. 2000;92(23):1881–8.
You WC, Brown LM, Zhang L, et al. Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions. J Natl Cancer Inst. 2006;98(14):974–83.
Plummer M, Vivas J, Lopez G, et al. Chemoprevention of precancerous gastric lesions with antioxidant vitamin supplementation: a randomized trial in a high-risk population. J Natl Cancer Inst. 2007;99(2):137–46.
Taylor PR. Prevention of gastric cancer: a miss. J Natl Cancer Inst. 2007;99(2):101–3.
Wu YQ, Liu HM, Chai X. Analysis of factors influencing disease progression and mucosal outcome in patients with chronic Atrophic gastritis treated with folic acid and Helicobacter pylori. Jiangsu Medicine. 2018;44(11):1283–6.
Dai YQ, Ye ZD, Huang HH. Long term effects of Helicobacter pylori plus folic acid in patients with chronic Atrophic gastritis. World J Chin Dig. 2017;25(19):1777–82.
Wei X, Qin DP. Systematic review of traditional Chinese medicine in the treatment of chronic Atrophic gastritis with dysplasia. J Zhejiang Chin Med Univ. 2013;37(7):864–9.
Li F, Han J. Meta-analysis on effect of traditional Chinese medicine on gastric epithelial dysplasia. Chin Med Bulletin. 2017;23(14):108–12.
Yang XY, Wu YL, Zhu YH, et al. A study on the treatment and prognosis of low-grade intraepithelial neoplasia of gastric mucosa with vernal fortification and folic acid. Theory Pract Inter Med. 2013;8(1):24–8.
Cao YJ, Qu CM, Wu JH, et al. Efficacy of folic acid combined with metoclopramide in the treatment of Atrophic gastritis precancerous lesions. World J Chin Dig. 2013;21(30):3261–4.
Feng RB. Clinical study of MORODAN combined with folic acid in the treatment of chronic Atrophic gastritis with dysplasia. Hebei Tradit Chin Med. 2011;33(6):865–7.
Zhong GX, Li SH. Evaluation of the quality of clinical randomized controlled trial reports for acupuncture treatment of chronic Atrophic gastritis based on CONSORT and STRICTA. Lishizhen Med Mater Med Res. 2013;24(4):983–6.
Li JH, Feng Y, Luo LT. Data analysis and quality evaluation of TCM literature on chronic gastritis. World Tradit Chin Med. 2013;8(12):1490–2.
Liu S, Su ZQ, Liu XY, et al. PubMed and web of science database: a literature analysis of the current status of traditional Chinese medicine in treating chronic atrophic gastritis. Chin J Exp Pharm. 2021;27(6):149–58.
Kenneth FS, Douglas GA, David M, the CONSORT Group. Consort 2010 statement: report an update to the guidelines for parallel-controlled randomized clinical trials. J Integr Chin West Med. 2010;8(7):604–12.
Wang P, Zhang BH, Wang FY, Tang XD. Efficacy evaluation of gastric precancerous lesions. Med Philos. 2015;36(539):18–20.
Li Y. Morphologic and molecular biological study of gastric dysplasia and dysplasia. Beijing: Peking Union Medical College Hospital; 2012.
Experts who participated in the development of this guide are as follow: Bai Wenyuan (The Second Hospital of Hebei Medical University), Bai Jianying (Chongqing Xinqiao Hospital), Chen Guangyong (Beijing Friendship Hospital, Capital Medical University), Chen Jie (Peking Union Medical College Hospital, Chinese Academy of Medical Sciences), Chen Shengliang (Renji Hospital affiliated with Shanghai Jiao Tong University School of Medicine), Chen Yingxuan (Renji Hospital affiliated with the Shanghai Jiao Tong University School of Medicine), Dang Tong (The Second Affiliated Hospital of Baotou Medical University), Ding Shigang (Peking University Third Hospital), Fan Xiangshan (Drum Tower Hospital affiliated with the Nanjing University School of Medicine), Hao Jianyu (Beijing Chaoyang Hospital, Capital Medical University), He Song (The Second Affiliated Hospital of Chongqing Medical University), Hu Bing (West China Hospital of Sichuan University), Hu Ling (Institute of the Spleen and Stomach, Guangzhou University of Traditional Chinese Medicine), Huang Shaogang (Guangdong Province Hospital of Traditional Chinese Medicine), Huo Lijuan (First Affiliated Hospital of Shanxi Medical University), Ji Guang (Shanghai University of Traditional Chinese Medicine), Ke Xiao (Second People's Hospital of Fujian Province), Lan Yu (Beijing Jishuitan Hospital), Li Huizhen (Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine), Li Jingnan (Peking Union Medical College Hospital, Chinese Academy of Medical Sciences), Li Junxiang (Oriental Hospital, Beijing University of Chinese Medicine), Li Li (Guanganmen Hospital, China Academy of Chinese Medical Sciences), Li Peng (Beijing Friendship Hospital, Capital Medical University), Li Yanping (Chongqing Traditional Chinese Medicine Hospital), Li Yan (Shengjing Hospital affiliated with China Medical University), Liu Feng (Shanghai Tenth People's Hospital), Liu Fengbin (The First Affiliated Hospital of Guangzhou University of Chinese Medicine), Liu Li (Shaanxi University of Chinese Medicine), Lu Yuan Yuan (First Affiliated Hospital of the Air Force Medical University), Lu Bin (First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine), Miao Xinpu (Hainan Provincial People's Hospital), Peng Guiyong (Chongqing Southwest Hospital), Ren Shunping (Shanxi University of Traditional Chinese Medicine Affiliated Hospital), Shen Huiqin (Second Hospital of Shanxi Medical University), Shen Hong (Jiangsu Provincial Hospital of Traditional Chinese Medicine), Sheng Jianqiu (The Seventh Medical Center of Chinese People's Liberation Army General Hospital), Sheng Weiqi (Fudan University Affiliated Tumor Hospital), Shi Yongquan (First Affiliated Hospital of the Air Force Medical University), Shi Zhaohong (Wuhan Integrated Traditional Chinese and Western Medicine Hospital), Tang Xudong (Institute of Spleen and Stomach Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences), Tang Yanping (Tianjin Integrated Traditional Chinese and Western Medicine Hospital, Nankai Hospital), Tang Zhipeng (Affiliated with Shanghai University of Traditional Chinese Medicine) Longhua Hospital), Wang Bangmao (Tianjin Medical University General Hospital), Wang Bin (Army Military Medical University Daping Hospital), Wang Chuijie (Liaoning University of Traditional Chinese Medicine Hospital), Wang Dong (Shanghai Jiaotong University Medical College Ruijin Hospital), Wang Fengyun (Institute of Spleen and Stomach Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences), Wen Yandong (Institute of Spleen and Stomach Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences), Xie Sheng (First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine), Xu Jinkang (Kunshan Traditional Chinese Medicine Hospital), Yang Qian (Hebei Province, Chinese Medicine Hospital), Yang Shiming (Xinqiao Hospital), Zhai Huihong (Beijing Friendship Hospital, Capital Medical University), Zhang Shengsheng (Beijing Chinese Medicine Hospital, Capital Medical University), Zhang Shutian (Beijing Friendship Hospital, Capital Medical University), Zhao Wenxia (Henan The First Affiliated Hospital of the University of Traditional Chinese Medicine), Zhou Weixun (Peking Union Medical College Hospital, Chinese Academy of Medical Sciences), Zhu Ying (The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine).
This work was supported by the Administration of Traditional Chinese Medicine Digestive Refractory Disease Inheritance and Innovation Team Project (No. ZYYCXTD-C-C202010) and the Special Project for Director of Business Laboratory of Evidence-based Medicine Center of Traditional Chinese Medicine (2020YJSZX-5).
Ethics approval and consent to participate
Consent for publication
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
About this article
Cite this article
Wang, P., Li, P., Chen, Y. et al. Chinese integrated guideline on the management of gastric precancerous conditions and lesions. Chin Med 17, 138 (2022). https://doi.org/10.1186/s13020-022-00677-6
- Gastric precancerous conditions
- Gastric precancerous lesions; integrated medicine; diagnosis