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Background and Aim Accumulating evidence indicates a plausible association between inflammatory bowel diseases and the risk of adverse health outcomes. However, the conclusions are inconsistent. We aimed to perform an umbrella review of meta-analyses to appraise and grade the evidence of the association between inflammatory bowel diseases and the risk of adverse health outcomes. Methods Meta-analyses of observational studies that examined the associations between inflammatory bowel disease and the risk of adverse health outcomes in PubMed, EMBASE, and Web of Science were screened. Results This umbrella review identified 25 meta-analyses, which yielded 123 effect estimates for 60 unique putative health outcomes. Patients with inflammatory bowel diseases had a higher risk of adverse health outcomes, including multiple cancers, cardiovascular disease, adverse pregnancy outcomes, adverse oral outcomes, and other adverse events. Moreover, inflammatory bowel diseases caused greater harm to health based on the presented evidence. However, none of the evidence was classified as “high” quality, only 15% was classified as “moderate,” and 65% of outcomes were rated as “very low.” Conclusion Patients with inflammatory bowel diseases had a higher risk of adverse health outcomes and further studies should be conducted to draw firmer conclusions.

The purpose of this meta-analysis was to assess the associations between inflammatory bowel disease (IBD) and risk of the gastric, small bowel and colorectal cancer. We searched the PubMed and Web of Science for observational studies published before June 2020, and the quality of each included study was evaluated according to the Newcastle–Ottawa–Scale. Twenty-six studies comprising 531 449 IBD patients and more than 65 million reference individuals were included. Although IBD was significantly associated with 67% increased risk of the total gastric, small bowel and colorectal cancer. After stratifying by cancer location, IBD mainly increased the risk of intestinal cancer instead of gastric cancer. Furthermore, Crohn’s disease (CD) significantly increased the risk of both small bowel cancer and colorectal cancer, while ulcerative colitis (UC) only increased the risk of colorectal cancer. In subgroup analysis, associations between IBD and risk of total gastric, small bowel and colorectal cancer were similar between male and female, except for that male IBD patients but not female had a significantly higher risk of small bowel cancer. Additionally, IBD patients in different geographical areas had different associations with risk of various gastrointestinal tract cancers. IBD is mainly associated with increased risk of cancers in the lower gastrointestinal tract, including small bowel cancer and colorectal cancer. Because studies about the association between IBD and risk of gastric cancer and the populations in Asia are limited, more observational studies are required in the future.

There were controversies for the association between computed tomography (CT)-determined low skeletal muscle mass (SMM) and overall survival (OS) in gastric cancer (GC). In this study, we investigated whether cachexia could be a potential confounding variable for this issue.We retrospectively collected the patients of GC in our institution between July 2016 and January 2021. Preoperative SMM was determined by analyzing the skeletal muscle index of L3 with abdominal CT, and the cut-offs for low SMM were defined as52.4 (men) and 38.5 cmOf the 255 included GC patients, 117 (46%) were classified as having low SMM. Those with low SMM were associated with a higher level of circulating interleukin 6 and C reactive protein but a lower level of albumin than those of normal SMM. The univariate analysis showed that low SMM, tumor-node-metastasis (TNM) stage, body mass index (BMI), postoperative chemotherapy, and cachexia were significantly associated with OS, while in the multivariate analysis, only low SMM and TNM stage were significantly associated with OS. Kaplan-Meier survival curves with log-rank tests indicated that low SMM significantly predicted worse OS of GC. After grouping by cachexia, the low SMM significantly predicted worse OS in patients with cachexia instead of those without cachexia.CT-determined low SMM predicts worse OS of GC in patients with cachexia instead of those without cachexia, and greater attention should be paid to such patients with synchronous low SMM and cachexia.

Observational studies have reported an association between metabolic syndrome (MetS) and colorectal cancer risk with inconsistent risk estimates. We conducted this meta-analysis to evaluate the risk of colorectal cancer in individuals with MetS. PubMed, Embase, and Web of Science were searched for related studies from database inception to 21 January 2021. Risk estimates for colorectal cancer were extracted from individual articles and pooled using a fixed-effect or random-effect model according to the heterogeneity. MetS was significantly associated with a higher risk of colorectal cancer in both sexes (relative risk [RR] 1.36, 95% confidence interval [CI] 1.26–1.47, P

The efficacy of PD-1/PD-L1 blockades is heterogeneous in different molecular subtypes of gastric cancer (GC). In this study, we analyzed relevant clinical trials to identify the molecular subtypes associated with the efficacy of PD-1/PD-L1 blockades, and public datasets, patient samples, and GC cell lines were used for investigating potential mechanisms. We found that GC with EBV-positive, MSI-H/dMMR, TMB-H or PIK3CA mutant subtype had enhanced efficacy of PD-L1/PD-1 blockades. Also, differentially expressed genes of these molecular subtypes shared the same gene signature and functional annotations related to immunity. Meanwhile, CIBERSORT identified that the overlapping landscapes of tumor-infiltrating immune cells in the four molecular subtypes were mainly M1-like macrophages (M1). The relationships between M1 and clinical characteristics, M1, and gene signatures associated with PD-1/PD-L1 blockades also revealed that M1 was associated with improved prognosis and required for the efficacy of PD-L1/PD-1 blockades in GC. We identified that tumor-infiltrating CD68+CD163− macrophages could represent M1 calculated by CIBERSORT in clinical application, and CXCL9, 10, 11/CXCR3 axis was involved in the mechanism of CD68+CD163− macrophages in the enhanced efficacy of PD-L1/PD-1 blockades. In conclusion, CD68+CD163− macrophages are required for the efficacy of PD-L1/PD-1 blockades and expand the applicable candidates in GC patients without the molecular subtypes.

Background: Cancer-associated cachexia is characterized by ongoing loss of skeletal muscle and has a high incidence in gastric cancer. Although studies have focused on the effect of inflammatory cytokines on skeletal muscle loss, it is not clear whether inflammatory cytokines affect other physiological functions, particularly immunity in gastric cancer. Thus, we aim to investigate the relationships between circulating TNF-α, skeletal muscle and peripheral immune status in gastric cancer.Methods: Totally 392 gastric cancer patients in cohort A and 60 gastric cancer patients in cohort B were selected from the prospective cohort study NCT03115931 and ChiCTR1900026578 in West China Hospital, Sichuan University, respectively. Besides, human skeletal muscle myoblasts (HSMMs) and peripheral CD8+ T cells completed about 7 to 9 days successive TNF-α intervention with different concentrations. Results: From data in cohort A, multivariate analysis showed that preoperative weight loss ≥5% was associated with circulating TNF-α (P =0.001) and TNM stage (P =0.002). ROC curve indicated that cut-off point of 9.96 pg/ml for circulating TNF-α was an important warning of weight loss ≥5% in patient with gastric cancer. Before surgery, high circulating TNF-α (≥ 9.96 pg/ml) was associated with significantly lower body weight, skeletal muscle mass and handgrip strength but not fat mass. After radical surgery, high circulating TNF-α was also associated with significantly more loss of body weight and skeletal muscle mass instead of fat mass. In cohort B and vitro experiments, immunohistochemistry, western blot and flow cytometry identified that high TNF-α led to myofiber change, decreased expression of AMP-dependent protein kinase (AMPK) and phosphate-AMPK in skeletal muscle and increased myoblast apoptosis. Flow cytometry found that circulating TNF-α was not correlated with PD-1, LAG-3, TIM-3 and TIGIT expressed on peripheral CD8+ T cells, and TNF-α not only promoted the proliferation of CD8+ T cells but also increased their apoptosis ratio at higher concentration.Conclusions: In our study, we found that TNF-α could result in myofiber change, interfered glycometabolism of skeletal muscle, whereas promoted the proliferation of CD8+ T cells in gastric cancer during cachexia, and preoperative circulating TNF-α of more than 9.96 pg/ml could indicate a high risk of weight loss.

We read with interest the study by Axelrad et al 1 which reported that Crohn’s disease (CD) and UC were associated with nearly ninefold and twofold increased risk of small bowel cancer (SBC), respectively. However, there were also two observational studies2 3 suggesting that UC was not associated with risk of SBC. Because epidemiological studies about IBD and risk of SBC were controversial, to better understand this issue, we conducted this meta-analysis. We searched the PubMed and Web of Science for relevant studies published before 1 June 2020. We included observational studies investigating the associations between IBD and risk of SBC (including adenocarcinoma, neuroendocrine tumour and sarcoma) and reporting the HR, OR or other measures of association. The pooled OR and 95% CIs were estimated with random-effect model when the significant …