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Abstract Recent research has demonstrated a relationship between fruit and vegetable intake and gastrointestinal cancers, but the causality of these associations remains uncertain. This investigation sought to elucidate whether there is a potential causal relationship between the intake of fruits and vegetables and the risk of gastrointestinal cancers. Employing two-sample Mendelian randomization (MR), this research explored the causative influence of consuming fruits (fresh and dried) and vegetables (salads/raw and cooked) on the susceptibility to gastrointestinal cancers. The UK Medical Research Council-Integrative Epidemiology Unit (MRC-IEU) provided the summary statistics for these exposure variables, while the summary statistics for outcome data came from four other data sources. Univariable and multivariable MR were performed using inverse variance-weighted (IVW), MR-Egger, weighted media (WM), and Lasso model methods. Besides, multiple methods were employed for sensitivity analyses to guarantee the robustness of the findings, including MR-Egger intercept, Cochran’s Q test, and MR-PRESSO. Furthermore, the Phenoscanner V2 database was employed to identify possible confounders. The main analysis of univariable MR found that dried fruit consumption provided protection against pancreatic and oral cavity/pharyngeal cancers. However, this correlation becomes non-significant when potential confounders such as smoking, drinking, and body mass index (BMI) are accounted for. Furthermore, neither univariate nor multivariate MR analyses revealed enough data to prove a causal relationship between the intake of fresh fruit, vegetables (including salad/raw and cooked), and gastrointestinal cancers. There is insufficient evidence for a causal association between the consumption of fruits and vegetables and the occurrence of gastrointestinal cancers. Further empirical research is needed to corroborate these dietary factors’ role in the etiology of gastrointestinal cancers.

Digestive system cancers are prevalent diseases with a high mortality rate, posing a significant threat to public health and economic burden. The diagnosis and treatment of digestive system cancer confront conventional cancer problems, such as tumor heterogeneity and drug resistance. Single-cell sequencing (SCS) emerged at times required and has developed from single-cell RNA-seq (scRNA-seq) to the single-cell multi-omics era represented by single-cell spatial transcriptomics (ST). This article comprehensively reviews the advances of single-cell omics technology in the study of digestive system tumors. While analyzing and summarizing the research cases, vital details on the sequencing platform, sample information, sampling method, and key findings are provided. Meanwhile, we summarize the commonly used SCS platforms and their features, as well as the advantages of multi-omics technologies in combination. Finally, the development trends and prospects of the application of single-cell multi-omics technology in digestive system cancer research are prospected.

Abstract The role of skeletal muscle and adipose tissue in the progression of cancer has been gradually discussed, but it needs further exploration. The objective of this study was to provide an in-depth analysis of skeletal muscle and fat in digestive malignancies and to construct novel predictors for clinical management. This is a retrospective study that includes data from Cancer Center, the First Hospital of Jilin University. Basic characteristic information was analyzed by T tests. Correlation matrices were drawn to explore the relationship between CT-related indicators and other indicators. Cox risk regression analyses were performed to analyze the association between the overall survivals (OS) and various types of indicators. A new indicator body composition score (BCS) was then created and a time-dependent receiver operating characteristic curve was plotted to analyze the efficacy of the BCS. Finally, a nomogram was produced to develop a scored-CT system based on BCS and other indicators. C-index and calibration curve analyses were performed to validate the predictive accuracy of the scored-CT system. A total of 575 participants were enrolled in the study. Cox risk regression model revealed that VFD, L3 SMI and VFA/SFA were associated with prognosis of cancer patients. After adjustment, BCS index based on CT was significantly associated with prognosis, both in all study population and in subgroup analysis according to tumor types (all study population: HR 2.036, P

Purpose: Previous observational studies have shown that green tea consumption is associated with a reduced incidence of digestive system cancers (DSCs). However, the observed association could be due to confounding factors. Therefore, we used a two-sample Mendelian randomization (MR) approach to assess the causal effect of green tea intake on the risk of five common DSCs. Methods: Independent genetic variants strongly associated with green tea consumption in European and East Asian populations were selected as instrumental variables in genome-wide association studies involving up to 64,949 European individuals and 152,653 East Asian individuals, respectively. The associations between genetic variants and DSCs were extracted from the FinnGen study and the Japan Biobank. The primary analysis was performed using random-effects inverse variance weighting (IVW). Other MR analyses, including weighted mode-based estimate, weighted-median, MR-Egger regression, Mendelian Randomization-Pleiotropy Residual Sum and Outlier (MR-PRESSO) analysis, were used for sensitivity analyses. In addition, a multivariate MR design was performed to adjust for smoking and alcohol consumption. Results: The IVW results showed no causal relationship between tea intake and DSCs risk in European population (esophagus cancer: odds ratio (OR) = 1.044, 95% confidence interval (CI) 0.992–1.099, p = 0.096; stomach cancer: OR = 0.988, 95% CI 0.963–1.014, p = 0.368; colorectal cancer: OR = 1.003, 95% CI 0.992–1.015, p = 0.588; liver cancer: OR = 0.996, 95% CI 0.960–1.032, p = 0.808; pancreatic cancer: OR = 0.990, 95% CI 0.965–1.015, p = 0.432). The MR-Egger regression, MR-PRESSO analysis and other methods also confirmed the reliability of the conclusion. Similarly, no significant association was found between green tea consumption and the incidence of DSCs among East Asians. This relationship is not significant even after adjusting for smoking and alcohol consumption (P > 0.05). Conclusion: Our study provides evidence that genetically predicted green tea intake is not causally associated with the development of DSCs in the European and East Asian population. [ABSTRACT FROM AUTHOR]

To investigate whether early-life exposure to the Great Famine of 1959–1961 in China was associated with the risk of digestive system cancer. The prospective cohort study involved 17 997 participants from the Kailuan Study (Tangshan, China) that began in 2006. All participants were divided into three groups based on their date of birth. The unexposed group (born from 1 October 1962 to 30 September 1964), fetal-exposed group (born from 1 October 1959 to 30 December 1961), and early-childhood-exposed group (born from 1 October 1956 to 30 December 1958). The Cox proportional hazards model was used to analyze the association between early famine exposure and digestive system cancer. During the mean follow-up period of (10.4 ± 2.2) years, a total of 223 digestive system cancer events occurred. Including 54 cases in the unexposed group (62.14/100 000 person-years), 57 cases in the fetal-exposed group (114.8/100 000 person-years), and 112 cases in the early-childhood-exposure group (122.2/100 000 person-years). After adjusting covariates, compared with the unexposed group, the HR and 95% CI were 1.85 (1.28, 2.69) for participants in the fetal-exposed group and 1.92 (1.38, 2.66) for participants in the early-childhood-exposed group. No interactions were observed in our study. After classifying digestive system cancers, the HR and 95% CI were 2.02 (1.03, 3.97) for colorectal cancer for participants in the fetal-exposed group and 2.55 (1.43, 4.55) for participants in the early-childhood-exposed group. The HR and 95% CI were (1.13, 3.83) of liver cancer for participants in the fetal-exposed group and 1.15 (0.63, 2.10) for participants in the early-childhood-exposed group. Early-life famine exposure was associated with a higher risk of digestive system cancer in adulthood. Fetal-exposed individuals might increase the risk of colorectal cancer and liver cancer, and early childhood-exposed might increase the risk of colorectal cancer. [ABSTRACT FROM AUTHOR]

Abstract Background and purpose The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in directing folate species towards nucleotide synthesis or DNA methylation. The MTHFR polymorphisms C677T and A1298C have been linked to cancer susceptibility, but the evidence supporting this association has been equivocal. To investigate the individual and joint associations between MTHFR C677T, A1298C, and digestive system cancer in a Chinese hypertensive population, we conducted a population-based case–control study involving 751 digestive system cancer cases and one-to-one matched controls from the China H-type Hypertension Registry Study (CHHRS). Methods We utilized the conditional logistic regression model to evaluate multivariate odds ratios (ORs) and 95% confidence intervals (CIs) of digestive system cancer. Results The analysis revealed a significantly lower risk of digestive system cancer in individuals with the CT genotype (adjusted OR: 0.71; 95% CI 0.52, 0.97; P = 0.034) and TT genotype (adjusted OR: 0.57; 95% CI 0.40, 0.82; P = 0.003; P for trend = 0.003) compared to those with the 677CC genotype. Although A1298C did not show a measurable association with digestive system cancer risk, further stratification of 677CT genotype carriers by A1298C homozygotes (AA) and heterozygotes (AC) revealed a distinct trend within these subgroups. Conclusion These findings indicate a potential protective effect against digestive system cancer associated with the T allele of MTHFR C677T. Moreover, we observed that the presence of different combinations of MTHFR polymorphisms may contribute to varying susceptibilities to digestive system cancer.

The inflammatory effect of dietary is strongly related to the development of cancer, therefore, the diet-related inflammatory index was developed as a methodological tool to investigate the relationship between dietary, inflammation and tumors. In this paper, we summarized the results on diet-related inflammatory indices and common cancers of the digestive system based on relevant cancer epidemiological studies. The available epidemiological evidence suggests that pro-inflammatory diet is associated with an increased risk of gastrointestinal malignancies, with the strongest association with colorectal cancer, followed by esophageal and gastric cancers, and then pancreatic cancer, and the least evidence of studies with liver cancer. Among these studies, the level of evidence for esophageal cancer is lower than colorectal cancer, the study of gastric cancer has gender differences and problems in adjusting for confounders, and the study of pancreatic cancer has heterogeneous results. In view of the current research progress and deficiencies, prospective studies or population-based cohort studies, as well as strengthening nutritional epidemiological studies related to common tumors such as liver cancer could be considered in the future. This review is expecting to provide basic information and scientific basis for strengthening the related healthy eating behavior promotion in the prevention and control of digestive system tumors. [ABSTRACT FROM AUTHOR]

Digestive cancers are among the leading causes of cancer death in the world. However, the mechanisms of cancer development and progression are not fully understood. Accumulating evidence in recent years pointing to the bidirectional interactions between gut dysbiosis and the development of a specific type of gastrointestinal cancer is shedding light on the importance of this "unseen organ"—the microbiota. This review focuses on the local role of the gut microbiota imbalance in different digestive tract organs and annexes related to the carcinogenic mechanisms. Microbiota modulation, either by probiotic administration or by dietary changes, plays an important role in the future therapies of various digestive cancers. [ABSTRACT FROM AUTHOR]

Background and purpose: The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in directing folate species towards nucleotide synthesis or DNA methylation. The MTHFR polymorphisms C677T and A1298C have been linked to cancer susceptibility, but the evidence supporting this association has been equivocal. To investigate the individual and joint associations between MTHFR C677T, A1298C, and digestive system cancer in a Chinese hypertensive population, we conducted a population-based case–control study involving 751 digestive system cancer cases and one-to-one matched controls from the China H-type Hypertension Registry Study (CHHRS). Methods: We utilized the conditional logistic regression model to evaluate multivariate odds ratios (ORs) and 95% confidence intervals (CIs) of digestive system cancer. Results: The analysis revealed a significantly lower risk of digestive system cancer in individuals with the CT genotype (adjusted OR: 0.71; 95% CI 0.52, 0.97; P = 0.034) and TT genotype (adjusted OR: 0.57; 95% CI 0.40, 0.82; P = 0.003; P for trend = 0.003) compared to those with the 677CC genotype. Although A1298C did not show a measurable association with digestive system cancer risk, further stratification of 677CT genotype carriers by A1298C homozygotes (AA) and heterozygotes (AC) revealed a distinct trend within these subgroups. Conclusion: These findings indicate a potential protective effect against digestive system cancer associated with the T allele of MTHFR C677T. Moreover, we observed that the presence of different combinations of MTHFR polymorphisms may contribute to varying susceptibilities to digestive system cancer. [ABSTRACT FROM AUTHOR]

Background: The enzyme phosphatidylethanolamine N-methyltransferase (PEMT) is responsible for synthesizing phosphatidylcholine by methylating phosphatidylethanolamine. We hypothesized that a polymorphism of the PEMT gene, rs7946, is involved in carcinogenesis. Objectives: We aimed to investigate the relationship between PEMT rs7946 and digestive system cancer and examine possible effect modifiers and mediators. Methods: We conducted a nested, case-control study within the China H-type Hypertension Registry Study, including 751 cases and 1:1 matched controls. To assess the association of PEMT rs7946 and digestive system cancer, we estimated odds ratios with 95% confidence intervals (CIs) using conditional logistic regression. We used the bootstrap test to examine the potential mediating effects of related metabolites. Results: Our results revealed that wild-type homozygous CC genotype carriers of PEMT rs7946 had a significantly increased risk [odds ratio (OR): 1.31; 95% CI: 1.04, 1.66; P = 0.023] compared with the TT/CT combined genotypes. The effect was found to be more pronounced in individuals with a lower choline-to-betaine ratio (<0.412, P-interaction = 0.021). Furthermore, the mediation analysis indicated that the choline-to-betaine ratio played a significant role in mediating 13.55% of the association between PEMT rs7946 and digestive system cancer (P = 0.018). Conclusions: Our study suggested that PEMT rs7946 may affect risk of digestive system cancer through direct and indirect pathways, and the choline-to-betaine ratio may partially mediate the indirect effect. This trial was registered at Chinese Clinical Trial Registry as ChiCTR1800017274. [ABSTRACT FROM AUTHOR]

Glycyrrhiza has a long history of applications and a wide range of pharmacological effects. It is known as the "king of all herbs". Glycyrrhiza is effective in clearing heat, detoxifying, relieving cough, and tonifying qi and has good bioactivity in multiple inflammatory, immune, and tumor diseases. This review aims to summarize the origin, distribution, and anti-digestive system tumor mechanism of glycyrrhiza and its homologous applications in medicine and food. The active compounds include triterpenoids, flavonoids, and coumarins, which are widely used in clinical treatments, disease prevention, and daily foods because of their "enhancement of efficacy" and "reduction of toxicity" against digestive system tumors. This paper reviews the use of glycyrrhiza in digestive system tumors and provides an outlook on future research and clinical applications. [ABSTRACT FROM AUTHOR]

Abstract Background The diagnostic criteria for abdominal obesity are usually waist circumference or waist-to-hip ratio. The magnitude of the risks for cancers of the digestive system and abdominal obesity is unknown. To assess whether abdominal obesity increases the risk of digestive cancer, we conducted a systematic review and meta-analysis of prospective cohort studies in a database. Methods PubMed, Embase, and Web of Science databases were searched from their inception to December 2022. The 9-star Newcastle Ottawa Scale was used to assess study quality. Pooled relative risks and 95% confidence intervals were calculated using fixed or random effect models respectively. The stability of the results was explored by one-by-one exclusion. Subgroup analysis was conducted to explore sources of heterogeneity. Publication bias was evaluated by Begg’s and Egger’s tests. Results A total of 43 cohort studies were included. There were 42 and 31 studies in the meta-analysis of waist circumference and waist-to-hip ratio on digestive system cancer, respectively. The results of the meta-analysis revealed that the greater waist circumference and waist-to-hip ratio were correlated with increased incidence of digestive system cancers: waist circumference: RR 1.48, 95% CI 1.38-1.59, p < 0.001; waist-to-hip ratio: RR 1.33, 95% CI 1.28-1.38, p = 0.001. Subgroup analysis by cancer type showed that higher WC and WHR would increase the prevalence of LC, PC, GC, EC, and CRC. The sensitivity analysis was conducted by a one-by-one elimination method, and the results of the meta-analysis remained stable. It is proved that the results were robust by the trim-and-fill method. Conclusions There was evidence to suggest that abdominal obesity increased the incidence of digestive cancer, it is necessary to take appropriate measures to reduce abdominal obesity. Waist circumference and waist-to-hip ratio may be better predictors of digestive system cancers. However, the association between waist circumference and digestive system cancer was greater, so more attention should be paid to measuring abdominal obesity with waist circumference.

Background: There is scant evidence regarding the effects of exercise type and duration on quality of life (QoL) in digestive system cancer (DSC) survivors. We aim to investigate the optimal type and duration of exercise to improve QoL for DSC survivors through a systematic review and network meta-analysis. Methods: A systematic literature search of PubMed, Embase, and Web of Science was performed. Eligibility for study inclusion was limited to studies that were randomized controlled trials involving all kinds of exercise in adult patients with DSCs, and the comparator was in standard care or other types of exercise. The primary outcome was QoL, including general health, physical health, mental health, and role function. Secondary outcomes included cancer-related symptoms such as fatigue, insomnia, depression, anxiety, and duration of hospital stay. The network meta-analyses were performed using a random-effect model. Results: The analysis included 32 eligible articles and a total of 2558 participants. Our primary outcome indicated that short-term aerobic exercise significantly enhanced general health (standardized mean difference (SMD) = 0.66, 95% credible intervals (CrIs): 0.05 to 1.30), and also contributed to a better mental health (SMD = 0.38, 95%CrI: –0.05 to 0.81) and role function (SMD = 0.48, 95%CrI: –0.27 to 1.20). Although without significant changes, short-term resistance exercise tended to increase the physical health of patients with DSCs (SMD = 0.69, 95%CrI: –0.07 to 1.50) and effective in alleviating fatigue (SMD = –0.77, 95%CrI: –1.50 to 0.01). Short-term aerobic exercise was related to a lower score of insomnia (SMD = –1.20, 95%CrI: –2.40 to 0.06), depression (SMD = –0.51, 95%CrI: –1.50 to 0.45), and anxiety (SMD = –0.45, 95%CrI: –1.30 to 0.34). All types of exercise related to a trend of declined hospital stays (–0.87 to –5.00 day). Long-term resistance exercise, however, was negatively associated with general health (SMD = –0.33, 95%CrI: –1.70 to 1.00), physical health (SMD = –0.18, 95%CrI: –1.30 to 0.90), and role function (SMD = –1.20, 95%CrI: –2.50 to 0.11). Conclusion: This study suggests that short-term aerobic exercise, with or without resistance exercise programs, enhances QoL (especially for general health) as well as relieves cancer-related symptoms for DSC survivors, while long-term resistance exercise may have negative effects, and thus should be adopted cautiously. These results provide important evidence for the management of DSCs.

Objectives: Summarize the progress and hot topic evolution of non-coding RNAs (ncRNAs) research in esophageal squamous cell carcinoma (ESCC) in recent years and predict future research directions.Methods: Relevant articles from the Web of Science until 31 October 2023 were obtained. Bibliometric analysis of included articles was performed using software (VOSviewer, CiteSpace, and Bibliometrix). The volume and citation of publications, as well as the country, institution, author, journal, keywords of the articles were used as variables to analyze the research trends and hot spot evolution.Results: 1,118 literature from 2008 to 2023 were retrieved from database, with 25 countries/regions, 793 institutions, 5,426 authors, 261 journals involved. Global cooperation was centered on China, Japan, and the United States. Zhengzhou University, an institution from China, had the highest publication. The most prolific author was Guo Wei, and the most prolific journal was Oncology Letters. Analysis of keywords revealed that the research in this field revolved around the role of ncRNAs in the occurrence, development, diagnosis, treatment, and prognosis of ESCC, mainly including micro RNAs, long non-coding RNAs, and then circular RNAs.Conclusion: Overall, research on ncRNAs in ESCC remains strong. Previous research has mainly focused on the basic research, with a focus on the mechanism of ncRNAs in the occurrence, development, diagnosis, treatment, and prognosis of ESCC. Combining current research with emerging disciplines to further explore its mechanisms of action or shifting the focus of research from preclinical research to clinical research based on diagnosis, treatment, and prognosis, will be the main breakthrough in this field in the future.

Background: The diagnostic criteria for abdominal obesity are usually waist circumference or waist-to-hip ratio. The magnitude of the risks for cancers of the digestive system and abdominal obesity is unknown. To assess whether abdominal obesity increases the risk of digestive cancer, we conducted a systematic review and meta-analysis of prospective cohort studies in a database. Methods: PubMed, Embase, and Web of Science databases were searched from their inception to December 2022. The 9-star Newcastle Ottawa Scale was used to assess study quality. Pooled relative risks and 95% confidence intervals were calculated using fixed or random effect models respectively. The stability of the results was explored by one-by-one exclusion. Subgroup analysis was conducted to explore sources of heterogeneity. Publication bias was evaluated by Begg's and Egger's tests. Results: A total of 43 cohort studies were included. There were 42 and 31 studies in the meta-analysis of waist circumference and waist-to-hip ratio on digestive system cancer, respectively. The results of the meta-analysis revealed that the greater waist circumference and waist-to-hip ratio were correlated with increased incidence of digestive system cancers: waist circumference: RR 1.48, 95% CI 1.38-1.59, p < 0.001; waist-to-hip ratio: RR 1.33, 95% CI 1.28-1.38, p = 0.001. Subgroup analysis by cancer type showed that higher WC and WHR would increase the prevalence of LC, PC, GC, EC, and CRC. The sensitivity analysis was conducted by a one-by-one elimination method, and the results of the meta-analysis remained stable. It is proved that the results were robust by the trim-and-fill method. Conclusions: There was evidence to suggest that abdominal obesity increased the incidence of digestive cancer, it is necessary to take appropriate measures to reduce abdominal obesity. Waist circumference and waist-to-hip ratio may be better predictors of digestive system cancers. However, the association between waist circumference and digestive system cancer was greater, so more attention should be paid to measuring abdominal obesity with waist circumference. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We examined multiple dietary patterns in relation to total digestive system cancer (DSC) incidence and death. METHODS: A total of 213,038 health professionals from the Health Professionals Follow-up Study (1986-2016), the Nurses' Health Study (1986-2018), and the Nurses' Health Study II (1991-2017) with no cancer diagnosis at baseline were analyzed. DSC incidence and death were estimated using time-varying Cox proportional hazards regression models. RESULTS: During up to 32 years of follow-up, 5,724 DSC cases accrued. Adherence to 8 healthy diet patterns was associated with a 7%-13% lower risk of DSC, particularly for digestive tract cancers. An inverse association with gastrointestinal tract cancer was also shown for all pattern scores except Alternate Mediterranean Diet and the healthful Plant-based Diet Index, with hazard ratios between 0.84 and 0.89. Inverse associations were shown for the reversed empirical dietary index for hyperinsulinemia (hazard ratio for 90th vs 10th percentile 0.64, 95% confidence interval [CI] 0.47-0.87) and the empirical dietary index associated with lower inflammation (rEDIP) (0.53, 95% CI 0.39-0.72) for stomach cancer, and for the rEDIP (0.58, 95% CI 0.37-0.92) for small intestine cancer. Among accessory cancers, the Alternate Healthy Eating Index-2010, alternate Mediterranean diet, and diabetes risk reduction diet were associated with a 43%-51% lower risk of liver cancer. The reversed empirical dietary index for hyperinsulinemia, rEDIP, and the Alternate Healthy Eating Index-2010 were inversely associated with the risk of fatal DSC. DISCUSSION: Adherence to healthy diets was associated with a lower risk of incident and fatal DSC, although the magnitude of the association varied slightly among the patterns. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether the volume of paracentesis for malignant ascites in acute care hospital wards is associated with survival and symptom relief. Methods: Patients with malignant ascites caused by digestive system cancer who underwent paracentesis between January 2010 and April 2022 were retrospectively analyzed from medical records. Collected data included the drainage volume per paracentesis procedure, survival time from the first paracentesis procedure, symptoms, and adverse events. According to the volume per paracentesis procedure, we divided the patients into the "small-drainage" (≤1500 mL) and "standard-drainage" (>1500 mL) groups. Results: The median age of the 144 patients was 69 years, 33% were female, and 64% had gastrointestinal cancer. The median survival from the first paracentesis procedure was 36 days. Eighty-nine (61.8%) and 55 (38.2%) patients were allocated to the small-drainage and standard-drainage groups, respectively. The median number of paracentesis procedures in the small-drainage and standard-drainage groups was 12 and 7, respectively (P =.001). The median survival in the small-drainage and standard-drainage groups was 50 and 44 days, respectively (P =.76). The multivariate analysis showed that the amount of drainage per session was not significantly associated with survival. Symptoms improved similarly in the 2 groups. No serious adverse events were observed. Conclusions: Paracentesis was demonstrated to be effective and safe, irrespective of the amount of fluid drained, for patients with malignant ascites in an acute care hospital. Thus, a strategy of limiting the amount of drainage is not associated with longer survival. [ABSTRACT FROM AUTHOR]

Digestive cancers are among the leading causes of cancer death in the world. However, the mechanisms of cancer development and progression are not fully understood. Accumulating evidence in recent years pointing to the bidirectional interactions between gut dysbiosis and the development of a specific type of gastrointestinal cancer is shedding light on the importance of this “unseen organ”—the microbiota. This review focuses on the local role of the gut microbiota imbalance in different digestive tract organs and annexes related to the carcinogenic mechanisms. Microbiota modulation, either by probiotic administration or by dietary changes, plays an important role in the future therapies of various digestive cancers.

• Short-term (≤12 weeks) aerobic exercise significantly enhanced general health for digestive system cancer (DSC) survivors. • Short-term aerobic exercise, with or without resistance exercise tended to benefit to physical health, mental health, role function and relieved cancer-related symptoms for patients with DSC. • Long-term (>12 weeks) resistance exercise was negatively associated with general health, physical health, and role function. There is scant evidence regarding the effects of exercise type and duration on quality of life (QoL) in digestive system cancer (DSC) survivors. We aim to investigate the optimal type and duration of exercise to improve QoL for DSC survivors through a systematic review and network meta-analysis. A systematic literature search of PubMed, Embase, and Web of Science was performed. Eligibility for study inclusion was limited to studies that were randomized controlled trials involving all kinds of exercise in adult patients with DSCs, and the comparator was in standard care or other types of exercise. The primary outcome was QoL, including general health, physical health, mental health, and role function. Secondary outcomes included cancer-related symptoms such as fatigue, insomnia, depression, anxiety, and duration of hospital stay. The network meta-analyses were performed using a random-effect model. The analysis included 32 eligible articles and a total of 2558 participants. Our primary outcome indicated that short-term aerobic exercise significantly enhanced general health (standardized mean difference (SMD) = 0.66, 95% credible intervals (CrIs): 0.05 to 1.30), and also contributed to a better mental health (SMD = 0.38, 95%CrI: –0.05 to 0.81) and role function (SMD = 0.48, 95%CrI: –0.27 to 1.20). Although without significant changes, short-term resistance exercise tended to increase the physical health of patients with DSCs (SMD = 0.69, 95%CrI: –0.07 to 1.50) and effective in alleviating fatigue (SMD = –0.77, 95%CrI: –1.50 to 0.01). Short-term aerobic exercise was related to a lower score of insomnia (SMD = –1.20, 95%CrI: –2.40 to 0.06), depression (SMD = –0.51, 95%CrI: –1.50 to 0.45), and anxiety (SMD = –0.45, 95%CrI: –1.30 to 0.34). All types of exercise related to a trend of declined hospital stays (–0.87 to –5.00 day). Long-term resistance exercise, however, was negatively associated with general health (SMD = –0.33, 95%CrI: –1.70 to 1.00), physical health (SMD = –0.18, 95%CrI: –1.30 to 0.90), and role function (SMD = –1.20, 95%CrI: –2.50 to 0.11). This study suggests that short-term aerobic exercise, with or without resistance exercise programs, enhances QoL (especially for general health) as well as relieves cancer-related symptoms for DSC survivors, while long-term resistance exercise may have negative effects, and thus should be adopted cautiously. These results provide important evidence for the management of DSCs. [Display omitted] [ABSTRACT FROM AUTHOR]

Immunotherapy has remained at the vanguard of promising cancer therapeutic regimens due to its exceptionally high specificity for tumor cells and potential for significantly improved treatment-associated quality of life compared to other therapeutic approaches such as surgery and chemoradiation. This is especially true in the digestive system, where high rates of mutation give rise to a host of targetable tumor-specific antigens. Many patients, however, do not exhibit measurable improvements under immunotherapy due to intrinsic or acquired resistance, making predictive biomarkers necessary to determine which patients will benefit from this line of treatment. Many of these biomarkers are assessed empirically by pathologists according to nuanced scoring criteria and algorithms. This review serves to inform clinicians and pathologists of extant and promising upcoming biomarkers predictive of immunotherapeutic efficacy among digestive system malignancies and the ancillary testing required for interpretation by pathologists according to tumor site of origin.

Background: Recently, PET/CT imaging with radiolabelled FAP inhibitors (FAPIs) has been widely evaluated in diverse diseases. However, rare report has been published using SPECT/CT, a more available imaging method, with [99mTc]Tc-labelled FAPI. In this study, we evaluated the potential effect of [99mTc]Tc-HFAPi in clinical analysis for digestive system tumours. Methods: This is a single-centre prospective diagnostic efficiency study (Ethic approved No.: XJTU1AF2021LSK-021 of the First Affiliated Hospital of Xi'an Jiaotong University and ChiCTR2100048093 of the Chinese Clinical Trial Register). Forty patients with suspected or confirmed digestive system tumours underwent [99mTc]Tc-HFAPi SPECT/CT between January and June 2021. For dynamic biodistribution and dosimetry estimation, whole-body planar scintigraphy was performed at 10, 30, 90, 150, and 240 min post-injection in four representative patients. Optimal acquisition time was considered in all the patients at 60–90 min post-injection, then quantified or semi-quantified using SUVmax and T/B ratio was done. The diagnostic performance of [99mTc]Tc-HFAPi was calculated and compared with those of contrast-enhanced CT (ceCT) using McNemar test, and the changes of tumour stage and oncologic management were recorded. Results: Physiological distribution of [99mTc]Tc-HFAPi was observed in the liver, pancreas, gallbladder, and to a lesser extent in the kidneys, spleen and thyroid. Totally, 40 patients with 115 lesions were analysed. The diagnostic sensitivity of [99mTc]Tc-HFAPi for non-operative primary lesions was similar to that of ceCT (94.29% [33/35] vs 100% [35/35], respectively; P = 0.5); in local relapse detection, [99mTc]Tc-HFAPi was successfully detected in 100% (n = 3) of patients. In the diagnosis of suspected metastatic lesions, [99mTc]Tc-HFAPi exhibited higher sensitivity (89.66% [26/29] vs 68.97% [20/29], respectively, P = 0.03) and specificity (97.9% [47/48] vs 85.4% [41/48], respectively, P = 0.03) than ceCT, especially with 100% (24/24) specificity in the diagnosis of liver metastases, resulting in 20.0% (8/40) changes in TNM stage and 15.0% (6/40) changes in oncologic management. Conclusion: [99mTc]Tc-HFAPi demonstrates a greater diagnostic efficiency than ceCT in the detection of distant metastasis, especially in identifying liver metastases. [ABSTRACT FROM AUTHOR]

Morning chronotype has been associated with a reduced risk of prostate and breast cancer. However, few studies have examined whether chronotype is associated with digestive tract cancer risk. We conducted a Mendelian randomization (MR) study to assess the associations of chronotype with major digestive tract cancers. A total of 317 independent genetic variants associated with chronotype at the genome‐wide significance level (P < 5 × 10−8) were used as instrumental variables from a genome‐wide meta‐analysis of 449 734 individuals. Summary‐level data on overall and six digestive tract cancers, including esophageal, stomach, liver, biliary tract, pancreatic and colorectal cancers, were obtained from the UK Biobank (11 952 cases) and FinnGen (7638 cases) study. Genetic liability to morning chronotype was associated with reduced risk of overall digestive tract cancer and cancers of stomach, biliary tract and colorectum in UK Biobank. The associations for the overall digestive tract, stomach and colorectal cancers were directionally replicated in FinnGen. In the meta‐analysis of the two sources, genetic liability to morning chronotype was associated with a decreased risk of overall digestive tract cancer (odds ratio [OR] 0.94, 95% confidence interval [CI]: 0.90‐0.98), stomach cancer (OR 0.84, 95% CI: 0.73‐0.97) and colorectal cancer (OR 0.92, 95% CI: 0.87‐0.98), but not with the other studied cancers. The associations were consistent in multivariable MR analysis with adjustment for genetically predicted sleep duration, short sleep, insomnia and body mass index. The study provided MR evidence of inverse associations of morning chronotype with digestive tract cancer, particularly stomach and colorectal cancers. [ABSTRACT FROM AUTHOR]

Immunotherapy has remained at the vanguard of promising cancer therapeutic regimens due to its exceptionally high specificity for tumor cells and potential for significantly improved treatment-associated quality of life compared to other therapeutic approaches such as surgery and chemoradiation. This is especially true in the digestive system, where high rates of mutation give rise to a host of targetable tumor-specific antigens. Many patients, however, do not exhibit measurable improvements under immunotherapy due to intrinsic or acquired resistance, making predictive biomarkers necessary to determine which patients will benefit from this line of treatment. Many of these biomarkers are assessed empirically by pathologists according to nuanced scoring criteria and algorithms. This review serves to inform clinicians and pathologists of extant and promising upcoming biomarkers predictive of immunotherapeutic efficacy among digestive system malignancies and the ancillary testing required for interpretation by pathologists according to tumor site of origin. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Malnutrition-related disease particularly occur in patients with digestive system cancer. The administration of oral nutritional supplements (ONSs) is one of the methods of nutritional support recommended for oncological patients. The primary aim of this study was to assess the consumption-related aspects of ONSs among patients with digestive system cancer. The secondary aim was to assess the impact of ONSs consumption on the quality of life of these patients. PATIENTS AND METHODS: The current study included 69 patients with digestive system cancer. The assessment of ONSs-related aspects among cancer patients was conducted using a self-designed questionnaire, which has been accepted by Independent Bioethics Committee. RESULTS: Among all patients, 65% of participants declared that they consumed ONSs. Patients consumed various types of ONSs. However, the most common were protein products (40%) and standard products (37.78%). Only 4.44% of patients consumed products with immunomodulatory ingredients. Nausea was the most commonly (15.56%) observed side effect after ONSs consumption. Considering particular types of ONSs, side effects were the most commonly declared by patients who consumed standard products (p=0.157). The easy product availability in the pharmacy was noted by 80% of participants. However, 48.89% of patients assessed the cost of ONSs as not acceptable (48.89%). 46.67% of studied patients did not observe the improvement of quality of life after ONSs consumption. CONCLUSIONS: We have demonstrated that patients with digestive system cancer consumed various period, amount, and types of ONSs. Side effects after ONSs consumption occur rarely. However, the improvement of quality of life related to ONSs consumption was not noted in almost half of participants. ONSs are easily available in pharmacy. [ABSTRACT FROM AUTHOR]

Digestive system cancers are important causes of morbidity and mortality worldwide. Cancer patients are more likely to commit suicide. The objective of this scoping review is to provide a comprehensive and updated summary of the existing literature on suicide among patients with digestive system cancers to identify the incidence and risk factors relevant to suicide in these populations. The PRISMA-Scr (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension protocol for scoping reviews) protocol was used. The review was based on relevant articles published prior to January 2022 in databases of Web of Science and PubMed. The authors identified 21 records that met the criteria for inclusion. Among the 21 articles, 18 (n = 85.7%) reported suicide risk factors, 21 (n = 100%) evaluated the incidence of suicide and 16 (n = 76.2%) involved the variation in suicide rates. Only one study comprehensively reported that the suicide rate for this population was 32.8 per 100,000 years and the standardized mortality ratio (SMR) was 1.91. Most suicides occurred in patients with pancreatic, esophageal, and gastric cancers. The factors associated with suicide in digestive system cancers included male gender, older age, the white race, single status, advanced stage of disease, and cancer metastasis. The most critical time for suicide was in the early post-diagnostic period. It is indispensable to identify suicide in these cancer patients, especially those with high-risk factors. In the future, more prospective research may be needed to provide more reliable support and care to prevent suicide. [ABSTRACT FROM AUTHOR]

Glycyrrhiza has a long history of applications and a wide range of pharmacological effects. It is known as the “king of all herbs”. Glycyrrhiza is effective in clearing heat, detoxifying, relieving cough, and tonifying qi and has good bioactivity in multiple inflammatory, immune, and tumor diseases. This review aims to summarize the origin, distribution, and anti-digestive system tumor mechanism of glycyrrhiza and its homologous applications in medicine and food. The active compounds include triterpenoids, flavonoids, and coumarins, which are widely used in clinical treatments, disease prevention, and daily foods because of their “enhancement of efficacy” and “reduction of toxicity” against digestive system tumors. This paper reviews the use of glycyrrhiza in digestive system tumors and provides an outlook on future research and clinical applications.

Cancers of the digestive system (DS), including esophageal, gastric, colorectal, liver, and pancreatic cancers, have a high incidence and mortality worldwide. Current cancer models cannot faithfully recapitulate the critical features of the original tumor, resulting in the failure of translation from basic research into clinical practice. More advanced cancer models are in urgent need of pathogenesis exploration and anticancer medicine development. Organoids are in vitro cultured three dimensional (3D) self-organizing organotypic structures derived from tissues and pluripotent stem cells, which faithfully mimic the histological features and preserve the genetic heterogeneity of the original tissues. Both normal and malignant organoids can now be efficiently established from the DS tissues of patients. In this review, we summarize the general methods to generate human DS organoids and their applications as a novel model in basic cancer research, preclinical medical practice, and precision medicine.

Immunohistochemical analysis of mismatch repair (MMR) protein expression is widely used to identify tumors with a deficient MMR (dMMR). MMR proteins (MLH1/PMS2 and MSH2/MSH6) work as functional heterodimers, which usually leads to the loss of expression in only one functional MMR heterodimer. Recently, there have been studies showing the simultaneous loss of immunoexpression in proteins of both heterodimers. Yet, this phenomenon has been rarely investigated. In this study, we retrospectively considered cases of different digestive system cancers (gastric cancer, ampullary cancer, small bowel cancer, colorectal cancer), which were immunohistochemically tested for dMMR within a 4-year period at our university hospital (n=352). Of the 103 cases showing dMMR, 5 cases (1.4% of all, 5.1% of dMMR cases) showed a concurrent loss of MLH1, PMS2 and MSH6 immunoexpression, whereas in the other 98 dMMR cases only one MMR heterodimer was affected. MLH1-/PMS2-/MSH6- cancer cases almost arose throughout the entire digestive tract: from the gastric antrum to the left colic flexur. To provide a comprehensive molecular characterization of this MLH1-/PMS2-/MSH6- immunophenotype, tumors were analyzed for microsatellite instability, MLH1 promotor hypermethylation and BRAF exon 15 status. Furthermore, we performed next-generation sequencing focusing on genes related to DNA repair. Here, we could detect pathogenic germline variants as well as multiple sporadic mutations in different genes involved in MMR and homologous recombination repair (HRR) respectively. The affected MMR/HRR-related genes were: ATM, BARD1, BRCA1, CDK12, CHEK1, CHEK2, FANCA, MLH1, MSH6, PALB2, TP53. Considering the biologic function of HRR/MMR proteins as potential drug targets and the low frequency of most of these mutations in digestive system cancers in general, their common occurrence in our MLH1-/PMS2-/MSH6-cases seems to be even more noteworthy, highlighting the need for recognition, awareness and further investigation of this unusual IHC staining pattern. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are a new series of noncoding RNAs (ncRNAs) that have been reported to be expressed in eukaryotic cells and have a variety of biological functions in the regulation of cancer pathogenesis and progression. The TME, as a microscopic ecological environment, consists of a variety of cells, including tumor cells, immune cells and other normal cells, ECM and a large number of signaling molecules. The crosstalk between circRNAs and the TME plays a complicated role in affecting the malignant behaviors of digestive system cancers. Herein, we summarize the mechanisms underlying aberrant circRNA expression in the TME of the digestive system cancers, including immune surveillance, angiogenesis, EMT, and ECM remodelling. The regulation of the TME by circRNA is expected to be a new therapeutic method. [ABSTRACT FROM AUTHOR]

Stomach, liver, and colon cancers are the most common digestive system cancers leading to mortality. Cancer leader genes were identified in the current study as the genes that contribute to tumor initiation and could shed light on the molecular mechanisms in tumorigenesis. An integrated procedure was proposed to identify cancer leader genes based on subcellular location information and cancer-related characteristics considering the effects of nodes on their neighbors in human protein-protein interaction networks. A total of 69, 43, and 64 leader genes were identified for stomach, liver, and colon cancers, respectively. Furthermore, literature reviews and experimental data including protein expression levels and independent datasets from other databases all verified their association with corresponding cancer types. These final leader genes were expected to be used as diagnostic biomarkers and targets for new treatment strategies. The procedure for identifying cancer leader genes could be expanded to open up a window into the mechanisms, early diagnosis, and treatment of other cancer types. [ABSTRACT FROM AUTHOR]

Immunohistochemical analysis of mismatch repair (MMR) protein expression is widely used to identify tumors with a deficient MMR (dMMR). MMR proteins (MLH1/PMS2 and MSH2/MSH6) work as functional heterodimers, which usually leads to the loss of expression in only one functional MMR heterodimer. Recently, there have been studies showing the simultaneous loss of immunoexpression in proteins of both heterodimers. Yet, this phenomenon has been rarely investigated. In this study, we retrospectively considered cases of different digestive system cancers (gastric cancer, ampullary cancer, small bowel cancer, colorectal cancer), which were immunohistochemically tested for dMMR within a 4-year period at our university hospital (n=352). Of the 103 cases showing dMMR, 5 cases (1.4% of all, 5.1% of dMMR cases) showed a concurrent loss of MLH1, PMS2 and MSH6 immunoexpression, whereas in the other 98 dMMR cases only one MMR heterodimer was affected. MLH1-/PMS2-/MSH6- cancer cases almost arose throughout the entire digestive tract: from the gastric antrum to the left colic flexur. To provide a comprehensive molecular characterization of this MLH1-/PMS2-/MSH6- immunophenotype, tumors were analyzed for microsatellite instability, MLH1 promotor hypermethylation and BRAF exon 15 status. Furthermore, we performed next-generation sequencing focusing on genes related to DNA repair. Here, we could detect pathogenic germline variants as well as multiple sporadic mutations in different genes involved in MMR and homologous recombination repair (HRR) respectively. The affected MMR/HRR-related genes were: ATM, BARD1, BRCA1, CDK12, CHEK1, CHEK2, FANCA, MLH1, MSH6, PALB2, TP53. Considering the biologic function of HRR/MMR proteins as potential drug targets and the low frequency of most of these mutations in digestive system cancers in general, their common occurrence in our MLH1-/PMS2-/MSH6- cases seems to be even more noteworthy, highlighting the need for recognition, awareness and further investigation of this unusual IHC staining pattern.

Allicin is the main active ingredient in freshly-crushed garlic and some other allium plants, and its anticancer effect on cancers of digestive system has been confirmed in many studies. The aim of this review is to summarize epidemiological studies and in vitro and in vivo investigations on the anticancer effects of allicin and its secondary metabolites, as well as their biological functions. In epidemiological studies of esophageal cancer, liver cancer, pancreatic cancer, and biliary tract cancer, the anticancer effect of garlic has been confirmed consistently. However, the results obtained from epidemiological studies in gastric cancer and colon cancer are inconsistent. In vitro studies demonstrated that allicin and its secondary metabolites play an antitumor role by inhibiting tumor cell proliferation, inducing apoptosis, controlling tumor invasion and metastasis, decreasing angiogenesis, suppressing Helicobacter pylori , enhancing the efficacy of chemotherapeutic drugs, and reducing the damage caused by chemotherapeutic drugs. In vivo studies further demonstrate that allicin and its secondary metabolites inhibit cancers of the digestive system. This review describes the mechanisms against cancers of digestive system and therapeutic potential of allicin and its secondary metabolites. [ABSTRACT FROM AUTHOR]

• Some EV-RNAs help to diagnosis for Digestive system cancer. • The RNA level of ANLN, ITGA6, KRT18 in EVs decrease in digestive cancer patients. • The RNA level of ANLN, ITGA6, KRT18 in EVs can be used for malignancy prediction. • The RNA level of MMP9 in EVs is correlated with pancreatic cancer progression. Poor prognosis of digestive system cancers is mainly owing to lack of accurate and timely diagnosis. The exploration of novel tumor biomarkers from extracellular vesicle (EV) might be helpful to clinical diagnosis for digestive system cancers. Several public databases were first used for a preliminary screening of candidate genes. The RNA levels of these candidate genes were then detected in cancer cell lines and the patients serum-derived EVs by PCR Array or digital PCR, respectively. We found that 4 EV-RNAs, ANLN, ITGA6, KRT18, and MMP9, had a lower level in gastrointestinal cancer patients than in benign gastrointestinal diseases patients and healthy controls, while 3 EV-RNAs, ANLN, ITGA6, and KRT18, had a lower level in pancreatic cancer patients than in benign pancreatic diseases patients or healthy individuals. And EV-RNA of MMP9 had a relatively higher level in advanced pancreatic cancer patients than in early-stage patients. Moreover, ROC analysis demonstrated that the determination of the above EV-RNAs could increase the ability of traditional tumor biomarkers to distinguish benign and malignant diseases. The serum-derived EV-RNAs of ANLN, ITGA6, KRT18, and MMP9 could be served as novel, non-invasive biomarkers for digestive system cancers. [ABSTRACT FROM AUTHOR]

Abstract Objectives This case–control study was aimed to investigate associations between HBV infection and extrahepatic digestive system cancers. Methods The patients of gastric, small intestinal, colonic, rectal, anal, biliary tract, and pancreatic cancers were retrospectively collected between 2016.5 and 2017.12. Simultaneously, the healthy controls were collected from the health check‐up registry, and cancer‐free status was confirmed based on medical records. Propensity score matching was performed to reduce bias. Multinomial logit model and conditional logistic regression model were used to assess the risk of individual cancer according to HBV serological markers and classifications. Results Totally, 4748 patients involving seven cancers, and 57,499 controls were included. After matching, HBsAg was associated with increased risk of gastric cancer (aOR = 1.39, 95% CI: 1.05–1.85), and anti‐HBs served as a protective factor for gastric (aOR = 0.72, 95% CI: 0.61–0.85), colonic (aOR = 0.73, 95% CI: 0.60–0.89), rectal (aOR = 0.73, 95% CI: 0.63–0.85), and pancreatic (aOR = 0.58, 95% CI: 0.42–0.82) cancers. Compared to subgroups with non‐infection and vaccination status, inactive HBsAg carriers and active HBV infection subgroup were correlated with gastric carcinogenesis (aOR = 1.41, 95% CI: 1.03–1.93). However, no clear association was found between HBV infection and other cancers. Conclusions HBV infection was potentially associated with an increased risk of gastric cancer. The development mechanism of HBV‐associated gastric cancer needs to investigate further.

Allicin is the main active ingredient in freshly-crushed garlic and some other allium plants, and its anticancer effect on cancers of digestive system has been confirmed in many studies. The aim of this review is to summarize epidemiological studies and in vitro and in vivo investigations on the anticancer effects of allicin and its secondary metabolites, as well as their biological functions. In epidemiological studies of esophageal cancer, liver cancer, pancreatic cancer, and biliary tract cancer, the anticancer effect of garlic has been confirmed consistently. However, the results obtained from epidemiological studies in gastric cancer and colon cancer are inconsistent. In vitro studies demonstrated that allicin and its secondary metabolites play an antitumor role by inhibiting tumor cell proliferation, inducing apoptosis, controlling tumor invasion and metastasis, decreasing angiogenesis, suppressing Helicobacter pylori, enhancing the efficacy of chemotherapeutic drugs, and reducing the damage caused by chemotherapeutic drugs. In vivo studies further demonstrate that allicin and its secondary metabolites inhibit cancers of the digestive system. This review describes the mechanisms against cancers of digestive system and therapeutic potential of allicin and its secondary metabolites.

Abstract Digestive system cancers are associated with high morbidity and mortality. Chemotherapy and radiotherapy are the main treatment modalities for these cancers. However, the development of therapy resistance leads to high rates of tumor recurrence and metastasis, resulting in dismal prognosis. Long non-coding RNA (LncRNA) H19, one of the most intriguing non-coding RNAs, has been shown to play a key role in the development and therapy resistance of various digestive system cancers (including hepatocellular carcinoma, colorectal cancer, pancreatic ductal adenocarcinoma, esophageal carcinoma, gastric cancer, and biliary system cancer) by regulating the abnormal expression of genes. In this review, we discuss the potential mechanisms of LncRNA H19 related therapy resistance in the context of digestive system cancers. LncRNA H19 is a potential novel therapeutic target for amelioration of cancer therapy resistance.

Objective To analyze the cancer mortality and epidemiological characteristics of digestive system cancer in Xianyou County, Fujian Province, and to provide a scientific evidence for formulating preventive measures for digestive system cancer. Methods Excel and SPSS software were used to collect the monitoring data of digestive system cancer death in Xianyou County from 2014 to 2018, and then analyzed the mortality, the standardized rate (according to the Chinese 2000 population census) and the cause of death. Results From 2014 to 2018, the deaths of malignant tumors in Xianyou County accounted for 35.00% of all deaths. Among them, the four common digestive system malignant tumors (gastric cancer, esophageal cancer, liver cancer and colorectal cancer) accounted for 62.44% of malignant tumors. Gastric cancer ranked first and accounted for 27.36%. Average annual rate of crude mortality and standardized mortality of malignant tumor in the digestive system were 108.93/105 and 89.34/105, respectively, and the ratio of male to female was 2.27 to 1. Significant differences were found between town and village, as the terrain gets lower, the death rate goes down gradually. Compared with the data of 2011-2012, the standardized death rate of gastric cancer, esophageal cancer and liver cancer were reduced by 29.71%, 23.92% and 12.06%, respectively, while the rate of colorectal cancer was increased by 28.80% and the average annual growth rate was 7.83%. Conclusion Although the death rates of gastric cancer, esophageal cancer and liver cancer have decreased significantly, the malignant tumor of the digestive system is still the main disease that causes the death of residents in Xianyou County, Putian City. Therefore, it is necessary to strengthen the education of health in order to achieve the early discovery, diagnosis and treatment.

PIWI-interacting RNAs (piRNAs) are a novel type of small non-coding RNAs (sncRNAs), which are 26–31 nucleotides in length and bind to PIWI proteins. Although piRNAs were originally discovered in germline cells and are thought to be essential regulators for germline preservation, they can also influence gene expression in somatic cells. An increasing amount of data has shown that the dysregulation of piRNAs can both promote and repress the emergence and progression of human cancers through DNA methylation, transcriptional silencing, mRNA turnover, and translational control. Digestive cancers are currently a major cause of cancer deaths worldwide. piRNAs control the expression of essential genes and pathways associated with digestive cancer progression and have been reported as possible biomarkers for the diagnosis and treatment of digestive cancer. Here, we highlight recent advances in understanding the involvement of piRNAs, as well as potential diagnostic and therapeutic applications of piRNAs in various digestive cancers.

Background Unrestrained eating behavior, as a potential proxy for diet frequency, timing, and caloric intake, has been questioned as a plausible risk factor for digestive system cancers, but epidemiological evidence remains sparse. Objectives We investigated prospectively the associations between unrestrained eating behavior and digestive system cancer risk. Methods Participants in the Nurses' Health Study who were free of cancer and reported dietary information in 1994 were followed for ≤18 y. Cox models were used to estimate HRs and 95% CIs for unrestrained eating (eating anything at any time, no concern with figure change, or both) and risk of digestive system cancers. Results During follow-up, 2064 digestive system cancer cases were documented among 70,450 eligible participants in analyses of eating anything at any time, In total, 2081 digestive system cancer cases were documented among 72,468 eligible participants in analyses of no concern with figure change. In fully adjusted analyses, women with the behavior of eating anything at any time had a higher risk of overall digestive system cancer (HR: 1.22; 95% CI: 1.10, 1.35), overall gastrointestinal tract cancer ((HR: 1.33; 95% CI: 1.18, 1.50), buccal cavity and pharynx cancer (HR: 1.50; 95% CI: 1.02, 2.21), esophageal cancer (HR: 1.62; 95% CI: 1.01, 2.62), small intestine cancer (HR: 1.92; 95% CI: 1.02,3. 59), and colorectal cancer (HR: 1.20; 95% CI: 1.04, 1.38), and a non–statistically significant increased risk of stomach cancer (HR: 1.54; 95% CI: 0.96,2.48), compared with women without this behavior. No statistically significant association was observed for pancreatic cancer and liver and gallbladder cancer. The combined effect of eating anything at any time and having no concern with figure change was associated with a significantly increased risk of overall digestive system cancer (HR: 1.27; 95% CI: 1.10, 1.46), overall gastrointestinal tract cancer (HR: 1.45; 95% CI: 1.23, 1.71), and colorectal cancer (HR: 1.34; 95% CI: 1.11, 1.63), compared with women exhibiting the opposite. Conclusions Unrestrained eating behavior was independently associated with increased risk of gastrointestinal tract cancers. The potential importance of unrestrained eating behavior modification in preventing gastrointestinal tract cancers should be noted. [ABSTRACT FROM AUTHOR]

Objectives: This case–control study was aimed to investigate associations between HBV infection and extrahepatic digestive system cancers. Methods: The patients of gastric, small intestinal, colonic, rectal, anal, biliary tract, and pancreatic cancers were retrospectively collected between 2016.5 and 2017.12. Simultaneously, the healthy controls were collected from the health check‐up registry, and cancer‐free status was confirmed based on medical records. Propensity score matching was performed to reduce bias. Multinomial logit model and conditional logistic regression model were used to assess the risk of individual cancer according to HBV serological markers and classifications. Results: Totally, 4748 patients involving seven cancers, and 57,499 controls were included. After matching, HBsAg was associated with increased risk of gastric cancer (aOR = 1.39, 95% CI: 1.05–1.85), and anti‐HBs served as a protective factor for gastric (aOR = 0.72, 95% CI: 0.61–0.85), colonic (aOR = 0.73, 95% CI: 0.60–0.89), rectal (aOR = 0.73, 95% CI: 0.63–0.85), and pancreatic (aOR = 0.58, 95% CI: 0.42–0.82) cancers. Compared to subgroups with non‐infection and vaccination status, inactive HBsAg carriers and active HBV infection subgroup were correlated with gastric carcinogenesis (aOR = 1.41, 95% CI: 1.03–1.93). However, no clear association was found between HBV infection and other cancers. Conclusions: HBV infection was potentially associated with an increased risk of gastric cancer. The development mechanism of HBV‐associated gastric cancer needs to investigate further. [ABSTRACT FROM AUTHOR]

Xiaoyun Zhang,1 Shijie Zhang,1 Qin He,1 Xiaojuan Gao,1 Lijun Yang,1 Peipei Xu,2 Rui Zhao,2 Qian Wang,3 Lina Zhang,4 Panpan Zhao5 1Department of Clinical Laboratory, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; 2Department of Clinical Laboratory, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; 3Department of Medical Laboratory, Fuwai Central China Cardiovascular Hospital, Zhengzhou, Henan 450052, China; 4Blood Transfusion Room, Fuwai Central China Cardiovascular Hospital, Zhengzhou, Henan 450052, China; 5Department of Clinical Laboratory, People’s Liberation Army 159 Hospital, Zhumadian, Henan 463000, China Abstract: The miR17-92 family is found to be aberrantly expressed and associated with clinicopathological characteristics in patients with various cancers, including digestive system cancers. However, its prognostic value is not yet established. Therefore, we performed a systematic review and meta-analysis to investigate the association between miR17-92-family expression and clinical outcomes in digestive system cancers. We searched the PubMed, Web of Science, Embase, and CNKI (Chinese) databases to retrieve eligible studies up to June 30, 2018. Prognostic data and clinicopathological features of overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were extracted to evaluate correlations of the miR17-92 family with digestive system cancers. We used HRs to assess association between miR17-92-family expression and cancers prognosis. A total of 30 qualifying studies involving 4,056 subjects were included in this meta-analysis. Our results indicated that expression levels of miR17-92 can predict poor OS (HR 1.21, 95% CI 1.03–1.39; P=0). However, there was no relationship between the miR17-92 family and DFS (HR 0.86, 95% CI 0.6–1.11; P=0.170) or PFS (HR 1.37, 95% CI 0.83–1.91; P=0). Moreover, miR17-92 was related to TNM stage (III/IV vs I/II, HR 1.37, 95% CI 1.17–1.570; P=0.012), but there was no relationship between miR17-92 and metastasis (HR 1.64, 95% CI 1.34–1.95; P=0.491) or tumor size (≥5 cm vs

Digestive system cancers are associated with high morbidity and mortality. Chemotherapy and radiotherapy are the main treatment modalities for these cancers. However, the development of therapy resistance leads to high rates of tumor recurrence and metastasis, resulting in dismal prognosis. Long non-coding RNA (LncRNA) H19, one of the most intriguing non-coding RNAs, has been shown to play a key role in the development and therapy resistance of various digestive system cancers (including hepatocellular carcinoma, colorectal cancer, pancreatic ductal adenocarcinoma, esophageal carcinoma, gastric cancer, and biliary system cancer) by regulating the abnormal expression of genes. In this review, we discuss the potential mechanisms of LncRNA H19 related therapy resistance in the context of digestive system cancers. LncRNA H19 is a potential novel therapeutic target for amelioration of cancer therapy resistance. [ABSTRACT FROM AUTHOR]

Numerous studies have indicated that abnormal activation of the HGF/c-Met signaling pathway can lead to cell proliferation, invasiveness, and metastasis of cancers of the digestive system. Moreover, overexpression of c-Met has been implicated in poor prognosis of patients with these forms of cancer, suggesting the possibility for HGF/c-Met axis as a potential therapeutic target. Despite the large number of clinical and preclinical trials worldwide, no significant positive success in the use of anti-HGF/c-Met treatments on cancers of the digestive system has been achieved. In this review, we summarize advanced development of clinical research on HGF/c-Met antibody and small-molecule c-Met inhibitors of cancers of the digestive system and provide a possible direction for future research.

Background: We aimed to evaluate the association between the vascular endothelial growth factor (VEGF) gene +936C>T polymorphism and digestive system tumors using a meta-analysis. Methods: Studies of the association between the VEGF+936C>T polymorphism and digestive system tumors published before December 2019 were searched in PubMed, EMBASE, Web of Sciences, the Chinese Biological and Medical Database (CBM), and the China National Knowledge Infrastructure (CNKI). The odds ratio and the corresponding 95% confidence interval were used as the effect indicators. A meta-analysis of original data was performed with different genetic models using the Stata 13.0 software. The reliability of the association was evaluated using the heterogeneity test, sensitivity analysis, false-positive report probability (FPRP), and bias test. Results: This meta-analysis included 37 publications with a total of 8568 digestive system tumor patients and 10,870 cases in the control populations. The overall combined analyses showed that the VEGF+936C>T gene polymorphism was significantly correlated with digestive system cancer susceptibility with the T allele increasing the risk of digestive system cancers. A stratified analysis based on ethnicity showed that the VEGF+936C>T gene polymorphism significantly increased the risk of digestive system tumors in both Asian and Caucasian populations. Additional stratified analyses based on tumor type showed that the VEGF +936C>T gene polymorphism was associated with colorectal cancer, oral cancer, and esophageal cancer. The sensitivity analysis (p < 0.2) and FPRP results also confirmed the reliability of these associations. Conclusions: This meta-analysis supported previous findings that the VEGF +936C>T gene polymorphism is significantly associated with an increased risk of the development of digestive system malignant tumors. This association still requires large-scale epidemiological studies for further validation. [ABSTRACT FROM AUTHOR]

The digestive system cancers are aggressive cancers with the highest mortality worldwide. In this study, we undertook a systematic investigation of the tumor immune microenvironment to identify diagnostic and prognostic biomarkers. The fraction of 22 immune cell types of patients were estimated using CIBERSORT. The least absolute shrinkage and selection operator (LASSO) analysis was carried out to identify important immune predictors. By comparing immune cell compositions in 801 tumor samples and 46 normal samples, we constructed the diagnostic immune score (DIS), showing high specificity and sensitivity in the training (area under the receiver operating characteristic curve [AUC] = 0.929), validation (AUC = 0.935), and different cancer type cohorts (AUC > 0.70 for all). We also established the prognostic immune score (PIS), which was an effective prognostic factor for relapse‐free survival in training, validation, and entire cohorts (P < .05). In addition, PIS provided a higher net benefit than TNM stage. A composite nomogram was built based on PIS and patients' clinical information with well‐fitted calibration curves (c‐index = 0.84). We further used other cohorts from Gene Expression Omnibus databases and obtained similar results, confirming the reliability and validity of the DIS and PIS. In addition, the unsupervised clustering analysis using immune cell proportions revealed 6 immune subtypes, suggesting that the immune types defined as having relatively high levels of M0 or/and M1 macrophages were the high‐risk subtypes of relapse. In conclusion, this study comprehensively analyzed the tumor immune microenvironment and identified DIS and PIS for digestive system cancers. [ABSTRACT FROM AUTHOR]

Background/Aims: Many studies have reported that PVT1 played important roles in diverse cancer types. But the systematic analysis of PVT1 in gastrointestinal cancers has not been inspected. Thus, we aimed to investigate clinical value of the long noncoding RNA PVT1 (lncRNA) expression in digestive system cancers. Methods: Eligible studies were collected from a number of databases (PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure and Wanfang database). Pooled hazard ratio (HR) or odds ratio (OR) with 95 % confidence interval (95 % Cl) were applied to assess the clinical significance of PVT1. Results: Data from 15 articles were included with a total of 2585 patients. Elevated PVT1 expression were significantly related to poor overall survival (OS) [HR = 1.86, 95% CI (1.44, 2.28); p

Objectives: Summarize the progress and hot topic evolution of non-coding RNAs (ncRNAs) research in esophageal squamous cell carcinoma (ESCC) in recent years and predict future research directions. Methods: Relevant articles from the Web of Science until 31 October 2023 were obtained. Bibliometric analysis of included articles was performed using software (VOSviewer, CiteSpace, and Bibliometrix). The volume and citation of publications, as well as the country, institution, author, journal, keywords of the articles were used as variables to analyze the research trends and hot spot evolution. Results: 1,118 literature from 2008 to 2023 were retrieved from database, with 25 countries/regions, 793 institutions, 5,426 authors, 261 journals involved. Global cooperation was centered on China, Japan, and the United States. Zhengzhou University, an institution from China, had the highest publication. The most prolific author was Guo Wei, and the most prolific journal was Oncology Letters. Analysis of keywords revealed that the research in this field revolved around the role of ncRNAs in the occurrence, development, diagnosis, treatment, and prognosis of ESCC, mainly including micro RNAs, long non-coding RNAs, and then circular RNAs. Conclusion: Overall, research on ncRNAs in ESCC remains strong. Previous research has mainly focused on the basic research, with a focus on the mechanism of ncRNAs in the occurrence, development, diagnosis, treatment, and prognosis of ESCC. Combining current research with emerging disciplines to further explore its mechanisms of action or shifting the focus of research from preclinical research to clinical research based on diagnosis, treatment, and prognosis, will be the main breakthrough in this field in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wu, Wang, Cheng, Cheng and Zhang.)

Background: The enzyme phosphatidylethanolamine N-methyltransferase ( PEMT ) is responsible for synthesizing phosphatidylcholine by methylating phosphatidylethanolamine. We hypothesized that a polymorphism of the PEMT gene, rs7946, is involved in carcinogenesis., Objectives: We aimed to investigate the relationship between PEMT rs7946 and digestive system cancer and examine possible effect modifiers and mediators., Methods: We conducted a nested, case-control study within the China H-type Hypertension Registry Study, including 751 cases and 1:1 matched controls. To assess the association of PEMT rs7946 and digestive system cancer, we estimated odds ratios with 95% confidence intervals (CIs) using conditional logistic regression. We used the bootstrap test to examine the potential mediating effects of related metabolites., Results: Our results revealed that wild-type homozygous CC genotype carriers of PEMT rs7946 had a significantly increased risk [odds ratio (OR): 1.31; 95% CI: 1.04, 1.66; P = 0.023] compared with the TT/CT combined genotypes. The effect was found to be more pronounced in individuals with a lower choline-to-betaine ratio (<0.412, P -interaction = 0.021). Furthermore, the mediation analysis indicated that the choline-to-betaine ratio played a significant role in mediating 13.55% of the association between PEMT rs7946 and digestive system cancer ( P = 0.018)., Conclusions: Our study suggested that PEMT rs7946 may affect risk of digestive system cancer through direct and indirect pathways, and the choline-to-betaine ratio may partially mediate the indirect effect.This trial was registered at Chinese Clinical Trial Registry as ChiCTR1800017274., (© 2024 The Authors.)