Time-restricted feeding (TRF) is a potent dietary intervention for improving metabolic diseases, including metabolic dysfunction-associated steatotic liver disease/metabolic dysfunction-associated steatohepatitis (MASLD/MASH). However, the mechanism of this efficacy has remained elusive. Here, we show that TRF improves MASLD, which is associated with a significant enrichment of Ruminococcus torques (R. torques). Mechanistically, R. torques suppresses the intestinal HIF-2α-ceramide pathway via the production of 2-hydroxy-4-methylpentanoic acid (HMP). We identify rtMor as a 4-methyl-2-oxopentanoate reductase that synthesizes HMP in R. torques. Finally, we show that either the colonization of R. torques or oral HMP supplementation can ameliorate inflammation and fibrosis in a MASH mouse model. These findings identify R. torques and HMP as potential TRF mimetics for the treatment of metabolic disorders.

ABSTRACT:A 66-year-old man with gastric signet-ring cell carcinoma underwent both 18 F-FDG and 18 FAl-NOTA-FAPI PET/CT imaging. There was no abnormal FDG activity in the stomach, but there was diffuse intense 18 FAl-NOTA-FAPI uptake in the known lesion and an adjacent metastasis.

A 66-year-old man with gastric signet-ring cell carcinoma underwent both F-18-FDG and 18FAl-NOTA-FAPI PET/CT imaging. There was no abnormal FDG activity in the stomach, but there was diffuse intense 18FAl-NOTA-FAPI uptake in the known lesion and an adjacent metastasis.

Colorectal cancer (CRC) is the most common cancer of the digestive system with high mortality and morbidity rates. Gut microbiota is found in the intestines, especially the colorectum, and has structured crosstalk interactions with the host that affect several physiological processes. The gut microbiota include CRC-promoting bacterial species, such as Fusobacterium nucleatum, Escherichia coli, and Bacteroides fragilis, and CRC-protecting bacterial species, such as Clostridium butyricum, Streptococcus thermophilus, and Lacticaseibacillus paracasei, which along with other microorganisms, such as viruses and fungi, play critical roles in the development of CRC. Different bacterial features are identified in patients with early-onset CRC, combined with different patterns between fecal and intratumoral microbiota. The gut microbiota may be beneficial in the diagnosis and treatment of CRC; some bacteria may serve as biomarkers while others as regulators of chemotherapy and immunotherapy. Furthermore, metabolites produced by the gut microbiota play essential roles in the crosstalk with CRC cells. Harmful metabolites include some primary bile acids and short-chain fatty acids, whereas others, including ursodeoxycholic acid and butyrate, are beneficial and impede tumor development and progression. This review focuses on the gut microbiota and its metabolites, and their potential roles in the development, diagnosis, and treatment of CRC.

Gastric cancers are highly heterogeneous malignant tumors. To reveal the relationship between differentiation status of cancer cells and tumor immune microenvironments in gastric cancer, single-cell RNA-sequencing was performed on normal mucosa tissue, differentiated gastric cancer (DGC) tissue, poorly differentiated gastric cancer (PDGC) tissue and neuroendocrine carcinoma (NEC) tissue sampled from surgically resected gastric cancer specimens. We identified the signature genes for both DGC and PDGC, and found that signature genes of PDGC strongly enriched in the epithelial-mesenchymal transition (EMT) program. Furthermore, we found that DGC tends to be immune-rich type whereas PDGC tends to be immune-poor type defined according to the density of tumor-infiltrating CD8+ T cells. Additionally, interferon alpha and gamma responding genes were specifically expressed in the immune-rich malignant cells compared with immune-poor malignant cells. Through analyzing the mixed adenoneuroendocrine carcinoma, we identified intermediate state malignant cells during the trans-differentiation process from DGC to NEC, which showed double-negative expressions of both DGC marker genes and NEC marker genes. Interferon-related pathways were gradually downregulated along the DGC to NEC trans-differentiation path, which was accompanied by reduced CD8+ cytotoxic T-cell infiltration. In summary, molecular features of both malignant cells and immune microenvironment cells of DGC, PDGC and NEC were systematically revealed, which may partially explain the strong tumor heterogeneities of gastric cancer. Especially along the DGC to NEC trans-differentiation path, immune-evasion was gradually enhanced with the decreasing activities of interferon pathway responses in malignant cells.

BACKGROUND The features of gastric cancer based on the anatomic site remain unknown in northern China patients. AIM To analyze gastric cancer features and associated trends based on the anatomical site in northern China patients. METHODS This cross-sectional study used incident gastric cancer case data from 10 Peking University-affiliated hospitals (2014 to 2018). The clinical and prevailing local features were analyzed. RESULTS A total of 10709 patients were enrolled, including antral (42.97%), cardia (34.30%), and stomach body (18.41%) gastric cancer cases. Cancer in the cardia had the highest male:female ratio, proportion of elderly patients, and patients with complications, including hypertension, diabetes, cerebrovascular, and coronary diseases (P < 0.001). gastric cancer involving the antrum showed the lowest proportion of patients from rural areas and accounted for the highest hospitalization rate and cost (each P < 0.001). The proportion of patients with cancer involving the cardia increased with an increase in the number of gastroesophageal reflux disease cases during the same period (P < 0.001). Multivariate analysis revealed that tumor location in the cardia increased the risk of in-hospital mortality (P = 0.046). Anatomical subsite was not linked to postoperative complications. CONCLUSION The features of gastric cancer based on the anatomical site differ between northern China and other regions, both globally and within the country. Social factors may account for these differences and should affect policy-making and clinical practice.

The burden of colorectal cancer is on the rise globally due to increasing prevalence. According to the Article by the Global Burden of Disease (GBD) 2019 Colorectal Cancer Collaborators, east Asia—especially China—has been greatly affected, with the highest all-age incidence (607 900 [95% uncertainty interval 521 805–708 420]) in mainland China, and the highest age-standardised incidence rates (62·0 [95% uncertainty interval 48·9–80·0] per 100 000) in Taiwan (province of China).1GBD 2019 Colorectal Cancer CollaboratorsGlobal, regional, and national burden of colorectal cancer and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.Lancet Gastroenterol Hepatol. 2022; (published online April 7.)https://doi.org/10.1016/S2468-1253(22)00044-9Google Scholar We believe there are a number of questions that could entail challenges and opportunities regarding colorectal cancer treatment in China. Disease patterns and treatment methods of colorectal cancer differ between anatomical subsites (usually distinguished as proximal colon, distal colon, and rectum). The locations of colorectal tumours—along with clinical features—also differ between patients in China and patients from other countries. For example, in Chinese patients, nearly half of tumours are located in the rectum.2Qu R Ma Y Tao L et al.Features of colorectal cancer in China stratified by anatomic sites: a hospital-based study conducted in university-affiliated hospitals from 2014 to 2018.Chin J Cancer Res. 2021; 33: 500-511Crossref PubMed Google Scholar Unique and distinctive treatment methods should be further explored, focusing on Chinese patients. A large increase of incident colorectal cancer cases was observed in young individuals (ie, those younger than 50 years) in the GBD study,1GBD 2019 Colorectal Cancer CollaboratorsGlobal, regional, and national burden of colorectal cancer and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.Lancet Gastroenterol Hepatol. 2022; (published online April 7.)https://doi.org/10.1016/S2468-1253(22)00044-9Google Scholar which has also been noted in Chinese patients.3Shi JF Wang L Ran JC et al.Clinical characteristics, medical service utilization, and expenditure for colorectal cancer in China, 2005 to 2014: overall design and results from a multicenter retrospective epidemiologic survey.Cancer. 2021; 127: 1880-1893Crossref PubMed Scopus (11) Google Scholar However, most guidelines in China still recommend that screening for colorectal cancer starts from age 50 years. Despite the potential downsides of over-screening, under-screening could lead to preventable deaths. The increasing evidence for a trend in younger-onset colorectal cancer in China urges us to rethink the recommended age at which people should be screened. What is the cause behind the growing trend in early-onset colorectal cancer in China? Popularisation of the meat-sweet diet (a hypercaloric diet high in processed sugar and red meat) among Chinese people, especially those younger than 40 years, has been proposed to be a causative factor, due to its detrimental metabolic consequences and effects on the progression of colorectal cancer.4Keum N Giovannucci E Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies.Nat Rev Gastroenterol Hepatol. 2019; 16: 713-732Crossref PubMed Scopus (775) Google Scholar However, detailed research among Chinese patients regarding the relation between colorectal cancer and risk factors remains scarce. Further research is needed to develop more thorough regional prevention strategies. The annual increase in incidence of—and mortality due to—colorectal cancer, increasing attention to quality of life, and the trend in early-onset disease suggest a need to revolutionise treatment methods. Surgery has long been considered the ultimate and most effective path for colorectal cancer treatment, but the long-term postoperative complications (including anal dysfunction) can affect quality of life (especially for Chinese patients, a higher proportion of whom have rectal cancer when compared with elsewhere in the world). Neoadjuvant chemotherapy has been increasingly accepted as a colorectal cancer treatment due to its potential benefits in long-term survival and quality of life.5O'Neill BD Brown G Heald RJ Cunningham D Tait DM Non-operative treatment after neoadjuvant chemoradiotherapy for rectal cancer.Lancet Oncol. 2007; 8: 625-633Summary Full Text Full Text PDF PubMed Scopus (175) Google Scholar However, use of neoadjuvant chemotherapy is not popular in China, and together with controversies in indication and scarcity of precise radiotherapy technology, represent challenges that need to be conquered in the future. We declare no competing interests. WF and ZZ have received funding from the National Natural Science Foundation of China (81972702 and 91959110 for WF and 62173005 for ZZ). ZZ and WF contributed equally. Editorial note: The Lancet Group takes a neutral position with respect to territorial claims in published text and institutional affiliations. Global, regional, and national burden of colorectal cancer and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019The increase in incidence rates in people younger than 50 years requires vigilance from researchers, clinicians, and policy makers and a possible reconsideration of screening guidelines. The fast-rising burden in low SDI and middle SDI countries in Asia and Africa calls for colorectal cancer prevention approaches, greater awareness, and cost-effective screening and therapeutic options in these regions. Full-Text PDF Open Access

Colorectal cancer (CRC) is the third most prevalent neoplasm and the second leading cause of cancer death worldwide. Microbiota and their products, such as bile acids (BAs), are important causal factors for the occurrence and development of CRC. Therefore, we performed 16S ribosomal RNA (16S rRNA) and liquid chromatography/mass spectrometry (LC–MS) to measure mucosal microbiota and BA composition in paired cancerous and noncancerous gut tissue samples from 33 patients with CRC at a hospital in Beijing. In cancerous tissues, we detected altered mucosal microbiota with increased levels of the genera Bacteroides, Curtobacterium, and Campylobacter and an increase in deoxycholic acid (DCA), which was the only BA elevated in cancerous tissues. Ex vivo coculture showed that the mucosal microbiota in cancerous tissues indeed had a stronger DCA production ability, indicating that DCA-producing bacteria are enriched in tumors. Results from the CCK8 and Transwell assays indicated that DCA enhances the overgrowth, migration, and invasion of CRC cell lines, and, through qPCR and Western blot analyses, downregulation of FXR was observed in CRC cell lines after DCA culture. We then verified the downregulation of FXR expression in cancerous tissues using our data and the TCGA database, and we found that FXR downregulation plays an important role in the development of CRC. In conclusion, differing mucosal microbiota, increased amounts of mucosal DCA, and lower FXR expression were demonstrated in cancerous tissues compared to normal tissue samples. The results of this study can be applied to the development of potential therapeutic targets for CRC prevention, such as altering mucosal microbiota, DCA, or FXR.

Abstract Background: Roux-en-Y (R-Y) reconstruction after distal gastrectomy in gastric cancer patients can cause Roux stasis syndrome (RSS), the pathogenic mechanism of which is unclear. This study retrospectively evaluated the risk factors for RSS.Material and methods: Patients who were pathologically diagnosed with gastric cancer and underwent distal gastrectomy with R-Y reconstruction between March 2014 and March 2021 were retrospectively analyzed. RSS occurrence was evaluated and examined for correlations with demographic and clinicopathological data. A nomogram was built using “R” package.Results: RSS was observed in 20/220 patients (9.1%), and there was a significant difference between males and females (11.9% vs. 3.9%, p = 0.049). The incidence of RSS tended to be higher in underweight (body mass index (BMI) < 18.5 kg/m2) and obese (BMI ≥ 28.0 kg/m2) patients (p = 0.043). The rates of smoking and nerve invasion were higher in patients with RSS, but statistical significance was not reached. There were no significant differences in other factors. A nomogram was built in which sex, BMI group, nerve invasion and smoking were incorporated to predict RSS (AUC = 0.71).Conclusions: Both male sex and a polarized BMI are independent risk factors for RSS after distal gastrectomy with R-Y reconstruction in gastric cancer patients. A nomogram including sex, BMI group, nerve invasion and smoking can predict RSS occurrence.Trial registration number:NCT04919577 (ClinicalTrials.gov)

Epidemiological studies have found an increased incidence of colorectal cancer (CRC) in people who undergo cholecystectomy compared to healthy individuals. After cholecystectomy, bile enters the duodenum directly, unregulated by the timing of meals. Disruption of the balance of bile acid metabolism and increased production of primary bile acids, which in turn affects the composition and abundance of intestinal microorganisms. The link among cholecystectomy, the gut microbiota, and the occurrence and development of CRC is becoming clearer. However, due to the complexity of the microbial community, the mechanistic connections are less well understood. In this review, we summarize the changes of gut microbiota after cholecystectomy and illuminate the potential mechanisms on CRC, such as inflammation and immune regulation, production of genotoxins, metabolism of dietary ingredients, activation of signaling pathways, and so on. By reviewing these, we aimed to unravel the interactions between the gut microbiota and its host and be better positioned to develop treatments for CRC after cholecystectomy.

AbstractBackgroundInformation on incidence of gastrointestinal stromal tumor (GIST), the most common type of mesenchymal tumor in gastrointestinal tract, was limited in China. This study aimed to estimate the incidence of GIST in urban population from mainland China in 2016.MethodsUrban Employee Basic Medical Insurance (UEBMI) and Urban Residence Basic Medical Insurance (URBMI) in China were used. The denominator of incidence was the total person‐years of insured individuals in 2016 in the database, covering approximately 0.43 billion individuals. The numerator was the number of incident GIST cases in 2016.ResultsThe crude incidence in 2016 was 0.40 per 100,000 person‐years (95% CI, 0.06–1.03). Male incidence was higher than female incidence (0.44 vs. 0.36, rate ratio: 1.22, p < 0.001). The mean age at diagnosis was 55.20 years (SD = 14.26) and the incidence among those aged 50 years or older was 2.63 times (0.84 vs. 0.32, p < 0.001) higher than those aged under 50. The highest incidence was observed in East China (2.29, 95% CI: 0.46–5.54).ConclusionsThe incidence of GIST in mainland China was lower than Europe, North America and Korea. The mean age at diagnosis of GIST in China was younger than that of Europe and Canada. This study provides useful information to further research, policy formulating and management of GIST.

OBJECTIVE:The clinical and biological characteristics of colorectal cancer have been found to differ depending on the anatomic site of the cancer. However, for Chinese patients, there is limited information on the proportion of cases at each site and the related features. In this study, we explored the location, distribution and other features of colorectal cancers at each anatomic site in Chinese patients. METHODS:We conducted a hospital-based study using hospitalization summary reports from 10 Peking University-affiliated hospitals from 2014 to 2018; the reports covered a total of 2,097,347 hospitalizations. Incident cases were chosen as the study population, and their epidemiological features were further analyzed. RESULTS:A total of 20,739 colorectal cancer patients were identified. Rectum was the most common location (48.3%) of the cancer, whereas the proportions of patients with distal and proximal colon cancer were 24.5% and 18.6%, respectively. Patients with rectal cancer were predominantly male and were the youngest for all anatomical sites (each P<0.001). The highest proportion of emergency admissions, the longest hospital stays and the highest hospitalization costs were found in patients with proximal colon cancer (each P<0.001). The proximal colon cancer subgroup included the highest proportions of patients with medical histories of cholecystectomy, cholecystolithiasis and/or gallbladder polyps and appendectomy (P=0.009, P<0.001 and P<0.001, respectively). The distal colon cancer subgroup included the highest proportions of patients with medical histories of diabetes and hypertension (P<0.001, respectively). CONCLUSIONS:The patterns of colorectal cancer observed in this study differ from those reported for Western patients and show a significantly higher proportion of patients with rectal cancer. Different epidemiological features were also found based on anatomic sites. Further studies based on tumor location should be conducted to facilitate more accurate screening and treatment.

BACKGROUND:Inflammatory response and nutritional status are associated with cancer development and progression. The purpose of this study was to explore whether the preoperative fibrinogen-albumin ratio index (FARI) is related to prognosis and chemoradiotherapy outcome of radical surgery after neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer (LARC). METHODS:In total, 123 patients with LARC who underwent radical surgery after NCRT between June 2012 and December 2018 were collected in this study. Time-dependent receiver operating characteristic (ROC) curve analysis was made to evaluate the ability of the markers for forecasting prognosis. The correlation between FARI and clinicopathological parameters was analyzed. The Kaplan-Meier survival analysis, univariate and multivariate analysis based on Cox proportional hazards models, and subgroup analysis were performed to evaluate overall survival (OS) and disease-free survival (DFS). A nomogram was constructed to evaluate the predictive role of FARI in DFS. RESULTS:The ROC curve analysis showed that the ability of FARI on DFS prediction was superior to those of other inflammatory markers and carcinoembryonic antigen (CEA) (P<0.05). Based on the Youden's index, the optimal cut-off value of FARI was 8.8%. High FARI patients (>8.8%) showed a poor response to NCRT and a decreased DFS rate (P<0.05). In addition, multivariate analysis revealed that FARI (HR=3.098, P=0.033), neutrophil-to-lymphocyte ratio (NLR), and postoperative T stage were independent prognostic factors for DFS in TNM stage III LARC patients. However, FARI failed to distinguish patients with poor OS. Harrell's concordance index (C-index) of the nomogram containing FARI (0.807) was obviously higher than that without it (0.732) among LARC patients who underwent radical surgery after NCRT. Moreover, multivariate analysis revealed FARI (OR=3.044, P=0.012) as an independent predictor for response to NCRT. CONCLUSION:Among LARC patients who underwent radical surgery after NCRT, preoperative FARI is an independent prognostic factor for DFS and an independent predictor for response to NCRT.

Aim Obstructive colon cancer can be treated by self-expanding metal stents (SEMS) prior to definitive surgery. However, the oncological outcome remains controversial, especially regarding whether stent placement or obstruction results in more perineural invasion (PNI) or lymphovascular invasion (LVI). This study aimed to compare clinical outcomes of emergency surgery (ES) and stent as bridge to surgery (SBTS) in patients with obstructive colon cancer. The pathological characteristics were also compared between obstructive and nonobstructive cancer. Methods This study included 880 patients (including 47 ES and 45 SBTS) admitted to Peking University Third Hospital from January 2010 to December 2018. Short-term and long-term outcomes were compared. The pathological differences between an equal number of obstructive and nonobstructive patients matched using propensity scores were investigated. Results SBTS patients had less intraoperative blood loss (P < 0.001), shorter ICU stay time (P = 0.007), lower incidence of colostomy (P < 0.001), and higher laparoscopic achievement (P < 0.001) than did ES patients. No pathological difference was found between the two groups. SBTS patients showed better overall survival (86.7% vs 68.1%, P = 0.029), but not disease-free survival (68.9% vs 59.6%, P = 0.211) than did ES patients. PNI was significantly higher in obstructive cancer than in nonobstructive cancer (29.3% vs 16.3%, P = 0.035). Conclusion SBTS had a lower incidence of short-term complications and did not affect long-term prognosis compared with that of ES, indicating that SBTS is a safe and effective treatment. Further, PNI may be associated with obstruction, but not with stent insertion.

Background Patients with stage II deficient mismatch repair (dMMR) show a better prognosis than patients with colorectal cancer (CRC) with proficient mismatch repair (pMMR). However, this beneficial effect is decreased in advanced stages of the disease. This study was conducted to investigate the prognostic value of dMMR in different stage and alterations in the tumor microenvironment. Methods This was a matched retrospective cohort study. Thirty-two patients with stage III&IV dMMR matched with 32 patients with stage I&II dMMR and 64 patients with pMMR were evaluated. Immunohistochemistry analysis was performed for the 64 patients with dMMR to explore the expression and prognostic effect of CD3, CD4, CD8, and PD-L1. Results Patients with stage III–IV dMMR showed no advantage in overall survival (OS) and disease-free survival (DFS) compared to patients with pMMR (P = 0.244, P = 0.667). No expression differences in CD3, CD4, CD8, and PD-L1 at the center of the tumor (CT) or invasive margin (IM) were found between patients with stage I&II and stage III&IV dMMR. High CD3 expression at the CT and high CD3 an CD4 expression at the IM improved both OS and DFS. High CD8 expression showed opposite prognostic value in patients with stage I&II and III&IV dMMR. A similar tendency was observed for PD-L1 expression. Conclusion Patients with stage III–IV dMMR showed no prognostic advantage over patients with pMMR. Expression of CD3, CD4, CD8, and PD-L1 was similar between stage I&II and III&IV dMMR CRC. High CD3 expression at the CT and high CD3 and CD4 expression at the IM can significantly improve patient prognosis. The opposite prognostic tendency of CD8 and PD-L1 for patients with stage I&II and III&IV dMMR may be relevant to CD8+T cell exhaustion and functional changes at inhibitory immune checkpoints.

Abstract Background: There is no consensus regarding which reconstruction methods are superior after laparoscopic distal gastrectomy (LDG). This study compared four reconstruction methods after LDG for gastric cancer. Methods: Literature in EMBASE, PubMed, and the Cochrane Library was screened to compare Billroth I (B-I), Billroth II (B-II), Roux-en-Y (RY), and uncut Roux-en-Y (URY) anastomoses after LDG for gastric cancer. A Bayesian network meta-analysis (NMA) was conducted to compare these methods. Results: Eighteen studies involving 4347 patients were eligible for our NMA. The operative time in RY anastomosis was longer than that in B-I and B-II anastomoses. Blood loss and risk of gastrointestinal motility dysfunction were greater with RY anastomosis than with URY or B-I anastomosis. Furthermore, URY anastomosis was superior to the other 3 reconstruction methods for preventing food residue. For remnant gastritis, RY anastomosis was significantly superior to B-I and B-II anastomoses, whereas URY anastomosis was significantly superior to B-II anastomosis. In addition, RY and URY anastomoses were better than B-I and B-II anastomoses for preventing bile reflux. Conclusions: URY anastomosis tended to be a more favorable reconstruction method after LDG due to its operative simplicity and reduced long-term complications.

Ingestion of jujube pits is a common clinical problem, which can be difficult to diagnose and life-threatening if accompanied with intestinal perforation and peritonitis. In this study, 18 cases of intestinal perforation caused by ingestion of jujube pits were reviewed and summarized to discuss the clinical characteristics, diagnosis and treatments.

Background: There is no consensus regarding which reconstruction methods are superior after laparoscopic distal gastrectomy (LDG). This study compared four reconstruction methods after LDG for gastric cancer. Methods: Literature in EMBASE, PubMed, and the Cochrane Library was screened to compare Billroth I (B-I), Billroth II (B-II), Rouxen-Y (RY), and uncut Roux-en-Y (URY) anastomoses after LDG for gastric cancer. A Bayesian network meta-analysis (NMA) was conducted to compare these methods. Results: Eighteen studies involving 4347 patients were eligible for our NMA. The operative time in RY anastomosis was longer than that in B-I and B-II anastomoses. Blood loss and risk of gastrointestinal motility dysfunction were greater with RY anastomosis than with URY or B-I anastomosis. Furthermore, URY anastomosis was superior to the other 3 reconstruction methods for preventing food residue. For remnant gastritis, RY anastomosis was significantly superior to B-I and B-II anastomoses, whereas URY anastomosis was significantly superior to B-II anastomosis. In addition, RY and URY anastomoses were better than B-I and B-II anastomoses for preventing bile reflux. Conclusions: URY anastomosis tended to be a more favorable reconstruction method after LDG due to its operative simplicity and reduced long-term complications.

Background Stage II colorectal cancer with microsatellite instability-high (MSI-H) has been proven to have a better prognosis. However, in advanced stage, this trend remains controversial. This study aimed to explore the prognostic role of MSI-H in stage III and IV colorectal cancer (CRC) through meta-analysis. Methods A comprehensive search was performed in PubMed, Cochrane Central Library, and Embase databases. All randomized clinical trials and non-randomized studies were included based on inclusion and exclusion criteria and on survival after a radical operation with or without chemotherapy. The adjusted log hazard ratios (HRs) were used to estimate the prognostic value between MSI-H and microsatellite-stable CRCs. The random-effects model was used to estimate the pooled effect size. Results Thirty-six studies were included. Randomized controlled trials (RCT) and non-RCT were analyzed separately. For stage III CRCs, pooled HR for overall survival (OS) was 0.96 (95% confidence interval [CI] 0.75–.123) in the RCT subgroup and 0.89 (95% CI 0.62–1.28) in the non-RCT subgroup. For disease-free survival (DFS), the HR for the RCT group was 0.83 (95% CI 0.65–1.07), similar to the non-RCT subgroup (0.83, 95% CI 0.65–1.07). Disease-specific survival (DSS) was also calculated, which had an HR of 1.07 (95% CI 0.68–1.69) in the non-RCT subgroup. All these results showed that MSI-H has no beneficial effects in stage III CRC. For stage IV CRC, the HR for OS in the RCT subgroup was 1.23 (95% CI 0.92–1.64) but only two RCTs were included. For non-RCT study, the combined HR for OS and DFS was 1.10 (95% CI 0.77–1.51) and 0.72 (95% CI 0.53–0.98), respectively, suggesting the beneficial effect for DFS and non-beneficial effect for OS. Conclusion For stage III CRC, MSI-H had no prognostic effect for OS, DFS, and DSS. For stage IV CRC, DFS showed a beneficial result, whereas OS did not; however, the included studies were limited and needed further exploration.