Digestive System Cancers Research Articles

Benefit-risk assessment of incretin and other anti-diabetic agents in type 2 diabetes using a stochastic multicriteria acceptability analysis model.

Benefit-risk assessment of incretin and other anti-diabetic agents in type 2 diabetes using a stochastic multicriteria acceptability analysis model.

The analysis of oral nutritional supplements related aspects among patients with digestive system cancer.

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.

Afatinib in combination with GEMOX chemotherapy as the adjuvant treatment in patients with ErbB pathway mutated, resectable gallbladder cancer: study protocol for a ctDNA-based, multicentre, open-label, randomised, controlled, phase II trial

IntroductionGallbladder cancer (GBC) is an aggressive type of digestive system cancer with a dismal outcome. Given the lack of effective treatment options, the disease rapidly reoccurs and 5-year survival rate...

The 10-month mortality rate among older patients treated for digestive system cancer during the first wave of the COVID-19 pandemic: The CADIGCOVAGE multicentre cohort study

IntroductionThe coronavirus disease 2019 (COVID-19) pandemic has had a dramatic impact on cancer diagnosis and care pathways. Here, we assessed the mid-term impact of the COVID-19 pandemic on older adults with cancer before, during and after the lockdown period in 2020. Materials and MethodsWe performed a retrospective, observational, multicentre cohort study of prospectively collected electronic health records. All adults aged 65 or over and having been newly treated for a digestive system cancer in our institution between January 2018 until August 2020 were enrolled. ResultsData on 7,881 patients were analyzed. Although the overall 10-month mortality rate was similar in 2020 vs. 2018–2019, the mortality rate among for patients newly treated in the 2020 post-lockdown period was (after four months of follow-up) significantly higher. A subgroup analysis revealed higher mortality rates for (i) patients diagnosed in the emergency department during the pre-lockdown period, (ii) patients with small intestine cancer newly treated during the post-lockdown period, and (iii) patients having undergone surgery with curative intent during the post-lockdown period. However, when considering individuals newly treated during the lockdown period, we observed lower mortality rates for (i) patients aged 80 and over, (ii) patients with a biliary or pancreatic cancer, and (iii) patients diagnosed in the emergency department. DiscussionThere was no overall increase in mortality among patients newly treated in 2020 vs. 2018–2019. Longer follow-up is needed to assess the consequences of the pandemic. A subgroup analysis revealed significant intergroup differences in mortality.

Clinicopathological and prognostic value of long non-coding RNA CCAT1 expression in patients with digestive system cancer.

Colon cancer associated transcript-1 (CCAT1) is known to play an important role in numerous types of human cancer, including bladder, prostate and ovarian cancer. However, a consistent perspective has not been established in digestive system cancer (DSC). To explore the prognostic value of CCAT1 in patients with DSC, a meta-analysis was performed. A systematic search of PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Chinese Biological Medical Literature database, Cochrane Library and WanFang database was applied to select eligible articles. Pooled odds ratios (ORs) or hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were calculated to estimate the effects of CCAT1 on pathological or clinical features. A total of 1,719 patients from 12 eligible articles were enrolled in the meta-analysis. The results revealed that elevated CCAT1 expression was significantly related to larger tumor size (OR, 1.81; 95% CI, 1.31-2.48), poorer differentiation (OR, 0.45; 95% CI, 0.31-0.64), earlier lymph node metastasis (OR, 3.14; 95% CI, 2.34-4.22) and advanced TNM stage (OR, 3.08; 95% CI, 2.07-4.59). In addition, high CCAT1 expression predicted a poorer outcome for overall survival rate (HR, 2.37; 95% CI, 2.11-2.67) and recurrence-free survival rate (HR, 2.16, 95% CI, 1.31-3.57). High expression levels of CCAT1 were therefore related to unfavorable clinical outcomes of patients with DSC. These results demonstrated that CCAT1 could serve as a prognostic predictor in human DSC.

Suicide in Digestive System Cancers: A Scoping Review

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.

The Role of CTNNA1 in Malignancies: An Updated Review.

Catenin alpha 1 (CTNNA1), encoding α-catenin, is involved in several physiological activities, such as adherens junction synthesis and signal transduction. Recent studies have suggested additional functions for CTNNA1 malignancies. This review systematically summarizes the varying functions of CTNNA1 in different tumors and briefly describes the diverse pathways and mechanisms involved in different types of tumors. CTNNA1 is abnormally expressed in leukemia and solid tumor such as cancers of digestive system, genitourinary system and breast, and it's related to the occurrence, development, and prognosis of tumors. In addition, the possible physiological processes involving CTNNA1, such as methylation, miRNA interference, or regulatory axes, similar to those of CDH1, SETD2, and hsa-miR-30d-5p/GJA1 are also summarized here. The precise mechanism of CTNNA1 in most cancers remains uncertain; hence, additional pre-clinical studies of CTNNA1 are warranted for potential early tumor diagnosis, prognosis, and treatment.

The association of serum serine levels with the risk of incident cancer: results from a nested case-control study.

Background: Cancer is associated with the dysregulation of serum serine levels, and tumor growth is supported by increased serine biosynthesis. This study aims to explore the association of serum serine levels with incident cancer risk in Chinese hypertensive adults. Materials and methods: 1391 patients with incident cancer and 1391 matched controls in terms of age, sex, and residence with cases in a 1 : 1 ratio were included in this nested case-control study. The serum serine concentrations were determined by liquid chromatography with tandem quadrupole mass spectrometry (LC-MS/MS) at the baseline. The associations of serum serine levels with the risk of overall, digestive system, non-digestive system, and lung cancers (the most common type) were assessed by conditional logistic regression. Results: When serum serine concentration was assessed as quartiles, a significantly higher risk of total cancer (OR = 1.32; 95% CI: 1.01-1.71; P = 0.038) was found in participants in the highest quartile (≥17.68 μg mL-1) compared with participants in the lowest quartile (<13.27 μg mL-1). Similar results were also observed for non-digestive system and lung cancers, but not for digestive system cancers. Significant associations of serum with overall cancer risk were found among all age subgroups, men, non-smokers, non-drinkers, and individuals with lower folic acid levels. Conclusion: High serum serine concentrations were associated with an increased risk of overall, non-digestive system, and lung cancers among Chinese hypertensive adult patients.

Cephalic Vein Cut Down for Total Implantable Venous Access Ports: A Retrospective Review of a Single Institution Series

The aim of this work was to describe the early and late success rates of cephalic vein cut down (CVC) in the implantation of totally implantable venous access ports (TIVAP) for chemotherapy treatment in oncological patients. This was a retrospective study of 1 047 TIVAP performed in a private institution between 2008 and 2021. The CVC with pre-operative ultrasound (PUS) was the initial approach. All cephalic veins (CVs) were mapped pre-operatively with Doppler ultrasound, measuring their diameter and course in oncological patients who required a TIVAP. With a CV diameter ≥ 3.2 mm TIVAP was carried out by CVC; with CV diameter < 3.2 mm, subclavian vein puncture (SVP) was performed. 1 047 TIVAPs were implanted in 998 patients. The mean age was 61.5 ± 11.5 years, 624 were women (65.5%). Male patients were significantly older and with a higher incidence of colonic, digestive system, and laryngeal cancer. Initially, TIVAP was indicated in 858 cases (82%) by CVC and 189 (18%) by SVP. The success rate was 98.5% for CVC and 98.4% for SVP. There were no complications for CVC (0%) but five early complications (2.5%) in the SVP group. The rates of late complications were 4.4% in the CVC group and 5.0% in the SVP group, foreign body infection being the most frequent (57.5% of the cases) (p= .85). The CVC or SVP using PUS for TIVAP deployment, performed through a single incision, is a safe and effective technique. This open but minimally invasive technique should be considered in oncological patients.

Genome-wide association studies identify miRNA-194 as a prognostic biomarker for gastrointestinal cancer by targeting ATP6V1F, PPP1R14B, BTF3L4 and SLC7A5.

The dysregulated genes and miRNAs in tumor progression can be used as biomarkers for tumor diagnosis and prognosis. However, the biomarkers for predicting the clinical outcome of gastrointestinal cancer (GIC) are still scarce. Genome-wide association studies were performed to screen optimal prognostic miRNA biomarkers. RNA-seq, Ago-HITS-CLIP-seq, western blotting and qRT-PCR assays were conducted to identify target genes of miR-194. Genome-wide CRISPR-cas9 proliferation screening analysis were conducted to distinguish passenger gene and driver gene. A total of 9 prognostic miRNAs for GIC were identified by global microRNA expression analysis. Among them, miR-194 was the only one miRNA that significantly associated with overall survival, disease-specific survival and progress-free interval in both gastric, colorectal and liver cancers, indicating miR-194 was an optimal prognostic biomarker for GIC. RNA-seq analysis confirmed 18 conservative target genes of miR-194. Four of them, including ATP6V1F, PPP1R14B, BTF3L4 and SLC7A5, were directly targeted by miR-194 and required for cell proliferation. Cell proliferation assay validated that miR-194 inhibits cell proliferation by targeting ATP6V1F, PPP1R14B, BTF3L4 and SLC7A5 in GIC. In summary, miR-194 is an optimal biomarker for predicting the outcome of GIC. Our finding highlights that miR-194 exerts a tumor-suppressive role in digestive system cancers by targeting ATP6V1F, PPP1R14B, BTF3L4 and SLC7A5.

The increasing incidence and high body mass index-related burden of gallbladder and biliary diseases-A results from global burden of disease study 2019.

Gallbladder and biliary diseases are common gastrointestinal conditions associated with huge socioeconomic costs and are considered risk factors for cardiovascular diseases and digestive system cancers. The prevalence and incidence of gallbladder and biliary diseases have not received enough attention from 1990 to 2019. Several non-communicable diseases were associated with the incidence of gallbladder and biliary diseases. It is necessary to clarify the change in the incidence and disability burden of gallbladder and biliary diseases worldwide. Data on high body mass index (BMI)-related disease burden and incidence, years of life lost prematurely, and years lived with disability (YLDs) due to gallbladder and biliary diseases were obtained from the Global Burden of Disease 2019. The estimated annual percentage change was calculated to qualify the gallbladder and biliary disease burden change. The global age-standardized incidence rate has increased from 585.35 per 100,000 (95% UI: 506.05-679.86) in 1990 to 634.32 per 100,000 (95% UI: 540.21-742.93) in 2019. And the increase in incidence was positively correlated with rising high BMI-related summary exposure value. The high BMI-related YLDs of gallbladder and biliary diseases have increased worldwide over time. Globally, the 25-49 age group suffered a rapid rise in incidence and high BMI attributable to the YLDs rate of gallbladder and biliary diseases. The global incidence and high BMI-related YLDs of gallbladder and biliary diseases remain prominent to increase over the past 30 years. Notably, the incidence and high BMI-related YLDs among people aged 25-49 years have rapidly increased over time. Therefore, high BMI should be emphasized in strategic priorities for controlling gallbladder and biliary diseases.

In vivo assessment of pharmacological potentials of different fractions of Fagonia olivieri DC

Introduction: Hemostasis mechanism involves blood coagulation as one of the step which is responsible for blood clot formation that restricts blood flow at site of injury. By inhibiting coagulation cascade and reducing thrombus formation, several cardiovascular diseases (CVD) and atherosclerosis can be prevented. Traditionally, Fagonia olivieri (zygophyllaceae) is reported in the treatment of diabetes, coughs, blood purifier, cooling agent, blood vascular diseases, digestive system disorders and cancer in initial stages. Objectives: Different fractions of F. olivieri methanolic extract were evaluated in this study for their anticoagulatory, anti-inflammatory and antidepressant potentials. Methodology: Anticoagulatory, anti-inflammatory and antidepressant potentials of ethyl acetate, butanol and aqueous extracts of F. olivieri were assessed using capillary tube experiment, carrageenan induced paw edema test and forced swim test respectively. Results: The results of this investigation have revealed that ethyl acetate and butanol fractions possess significant anticoagulatory potentials as compared to control (P=0.0002). Butanol extract showed highest anti-inflammatory activity. Maximum anti-depressant activity was shown by ethyl acetate followed by n-butanol and aqueous extracts. Conclusion: Hence, it can be concluded that F. olivieri exhibits anticoagulatory, anti-inflammatory and antidepressant potentials which justifies its use for the treatment of various disorders particularly blood vascular diseases.

The Association of Serum L-Carnitine Concentrations with the Risk of Cancer in Chinese Adults with Hypertension

The effect of serum L-carnitine (LC) concentrations on cancer risk remains unclear. This study aims to explore the association between serum LC and the risk of incident cancer. This is a case-control study, including 574 patients with incident cancer and 574 controls matched in a 1:1 ratio by age, sex, and residence, nested within the China H-Type Hypertension Registry Study (CHHRS). Conditional logistic regression analysis was used to assess the association of serum LC and incident cancer risk. When LC was assessed as quartiles, compared with patients with low LC (Q1), patients in the highest quartile (Q4) had a 33% (OR = 0.67, 95% CI: 0.46 to 0.99), 52% (OR = 0.48, 95% CI: 0.23 to 0.99), and 39% (OR = 0.61, 95% CI: 0.38 to 0.99) decreased risk of overall, digestive system, and non-digestive system cancer in the adjusted models, respectively. In subgroup analyses, an inverse association of LC with cancer risk was observed in individuals who were overweight (obese), who never drink, who never smoke, and who were female. In the mediation analysis, serum trimethylamine-N-oxide (TMAO) concentrations did not mediate the reversed association of LC with cancer risk. This study showed that serum LC concentrations had a protective impact on overall, digestive system, and non-digestive system cancer risk.

Clinical characteristics of digestive system cancers metastatic to the heart

Objective: To investigate the clinical features of patients with cardiac metastases from digestive system tumors. Methods: This retrospective study collected and analyzed the medical records of patients with cardiac metastases from digestive system tumors who received treatments in the Cancer Hospital, Chinese Academy of Medical Sciences between January 1999 and January 2021. Kaplan-Meier method was used for survival analysis. Results: A total of 19 patients were identified. The primary tumors were esophageal squamous cell carcinoma (n=7), gastric or gastroesophageal junction adenocarcinoma (n=6), hepatobiliary cancers (n=3) and colorectal cancers (n=3). 16 patients had pericardial metastases, 2 patients had right atrium metastases, and 1 patient had left ventricle metastasis. The most common symptom was dyspnea, which was present in 8 cases. 7 patients received locoregional treatment, while 11 patients underwent systemic therapies. The median overall survival from diagnosis of primary cancer was 31.4 months, and the median overall survival time from diagnosis of cardiac metastasis was 4.7 months. Conclusion: Cardiac metastasis from digestive system tumors is associated with low incidence and a poor prognosis. Systemic treatment remains the cornerstone of management, while novel anti-tumor drugs may improve therapeutic efficacy.

Dysbiosis: The first hit for digestive system cancer.

Gastrointestinal cancer may be associated with dysbiosis, which is characterized by an alteration of the gut microbiota. Understanding the role of gut microbiota in the development of gastrointestinal cancer is useful for cancer prevention and gut microbiota-based therapy. However, the potential role of dysbiosis in the onset of tumorigenesis is not fully understood. While accumulating evidence has demonstrated the presence of dysbiosis in the intestinal microbiota of both healthy individuals and patients with various digestive system diseases, severe dysbiosis is often present in patients with digestive system cancer. Importantly, specific bacteria have been isolated from the fecal samples of these patients. Thus, the association between dysbiosis and the development of digestive system cancer cannot be ignored. A new model describing this relationship must be established. In this review, we postulate that dysbiosis serves as the first hit for the development of digestive system cancer. Dysbiosis-induced alterations, including inflammation, aberrant immune response, bacteria-produced genotoxins, and cellular stress response associated with genetic, epigenetic, and/or neoplastic changes, are second hits that speed carcinogenesis. This review explains the mechanisms for these four pathways and discusses gut microbiota-based therapies. The content included in this review will shed light on gut microbiota-based strategies for cancer prevention and therapy.

Association between serum arginine levels and cancer risk: A community-based nested case-control study.

The effect of arginine on tumors appears to be bidirectional. The association of serum arginine with the risk of incident cancer remains uncovered at present. We aimed to investigate the prospective relationship of baseline serum arginine concentrations with the risk of incident cancer in hypertensive participants. A nested, case-control study with 1,389 incident cancer cases and 1,389 matched controls was conducted using data from the China H-Type Hypertension Registry Study (CHHRS). Conditional logistic regression analyses were performed to evaluate the association between serum arginine and the risk of the overall, digestive system, non-digestive system, and site-specific cancer. Compared with matched controls, cancer patients had higher levels of arginine (21.41 μg/mL vs. 20.88 μg/mL, p < 0.05). When serum arginine concentrations were assessed as quartiles, compared with participants in the lowest arginine quartile, participants in the highest arginine quartile had a 32% (OR = 1.32, 95% CI: 1.03 to 1.71), and 68% (OR = 1.68, 95% CI: 1.09 to 2.59) increased risk of overall and digestive system cancer, respectively, in the adjusted models. In the site-specific analysis, each standard deviation (SD) increment of serum arginine was independently and positively associated with the risk of colorectal cancer (OR = 1.35, 95% CI: 1.01 to 1.82) in the adjusted analysis. We found that hypertensive individuals with higher serum arginine levels exhibited a higher risk of overall, digestive system, and colorectal cancer.

Concurrent loss of MLH1, PMS2 and MSH6 immunoexpression in digestive system cancers indicating a widespread dysregulation in DNA repair processes.

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.

M6A-Related Genes Contribute to Poor Prognosis of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common and lethal digestive system cancers worldwide. N6-methyladenosine (m6A) modification plays an essential role in diverse critical biological processes and may participate in the development and progression of HCC. We downloaded transcriptome data and clinical data from TCGA as the training set. COX and LASSO screened prognostic m6A genes. ROC and Kaplan-Meier curve analysis evaluated the effectiveness of the model. ICGC and our center data were used as verification sets. We include the "writer (METTL3, METTL14, WTAP, KIAA1429, RBM15, ZC3H13)," the "reader (YTHDC1, YTHDC2, YTHDF1, YTHDF2, HNRNPC)," and the "eraser (FTO, ALKBH5)" in the study. We obtained YTHDF2, YTHDF1, METTL3, and KIAA1429 through differential analysis, survival analysis, and LASSO regression analysis. The prediction model was established based on the expression of these 4 molecules. HCC patients were divided into "high-risk" and "low-risk" groups to compare survival differences. The model suggested a poor prognosis in the validation sets. The four-m6A-related-gene combination model was an independent prognostic factor of HCC and could improve the prediction of the prognosis of HCC.

Outcomes of subjects who are lean, overweight or obese with nonalcoholic fatty liver disease: A cohort study in China.

The ability to determine the prognosis of lean nonalcoholic fatty liver disease (NAFLD) is essential for decision making in clinical settings. Using a large community-based Chinese cohort, we aimed to investigate NAFLD outcomes by body mass index (BMI). We used the restricted cubic splines method to investigate the dose-response relationship between BMI and outcomes in subjects with NAFLD and those without NAFLD. We included 73,907 subjects from the Kailuan cohort and grouped all subjects into four phenotypes by using NAFLD and BMI (<23 kg/m2 ). The probability of developing outcomes for individuals with lean NAFLD (LN), overweight/obese NAFLD (ON), overweight/obese non-NAFLD (ONN), and lean non-NAFLD (LNN) was estimated. We found a U-shaped association between BMI and death but a linear positive association concerning cardiovascular disease (CVD) after adjusting for age and other covariates. Compared with the LNN group, the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of the LN, ON, and ONN groups were 1.30 (1.14-1.49), 0.86 (0.80-0.91), 0.84 (0.80-0.89) for all-cause death, 2.61 (1.13-6.03), 0.74 (0.44-1.26), 1.10 (0.70-1.74) for liver-related death, 2.12 (1.46-3.08), 1.23 (0.99-1.54), 1.19 (0.98-1.43) for digestive system cancers, and 2.04 (1.40-2.96), 1.30 (1.05-1.61), 1.21 (1.01-1.46) for obesity-related cancers. Subjects with LN had a significantly higher risk of colorectal cancer and esophagus cancer. However, the ON group had the highest CVD risk (HR,1.39; 95% CI, 1.27-1.52). The LN group with hypertension had a higher risk of adverse outcomes, and those without hypertension had a similar risk compared to LNN. Conclusion: Subjects with LN may experience a higher risk of all-cause death, digestive system cancers, and obesity-related cancers than the other three groups but a lower risk of CVD than ON subjects. LN with hypertension may be a high-risk phenotype.

Efficacy of metformin therapy in patients with cancer: a meta-analysis of 22 randomised controlled trials

BackgroundTo investigate whether metformin monotherapy or adjunctive therapy improves the prognosis in patients with any type of cancer compared to non-metformin users (age ≥18).MethodsDatabases (Medline, Embase, and the Cochrane Central Register of Controlled Trials) and clinical trial registries (ClinicalTrials.gov; the World Health Organization International Clinical Trials Registry Platform) were screened for randomized, controlled trials (RCT) reporting at least progression-free survival (PFS) and/or overall survival (OS). Main outcome measures included hazard ratios (HR), and combined HRs and 95% confidence intervals (CI) were calculated using random-effects models.ResultsOf the 8419 records screened, 22 RCTs comprising 5943 participants were included. Pooled HRs were not statistically significant in both PFS (HR 0.97, 95% CI 0.82–1.15, I2 = 50%) and OS (HR 0.98, 95% CI 0.86–1.13, I2 = 33%) for patients with cancer between the metformin and control groups. Subgroup analyses demonstrated that metformin treatment was associated with a marginally significant improvement in PFS in reproductive system cancers (HR 0.86, 95% CI 0.74–1.00) and a significantly worse PFS in digestive system cancers (HR 1.45, 95% CI 1.03–2.04). The PFS or OS was observed consistently across maintenance dose, diabetes exclusion, median follow-up, risk of bias, and combined antitumoral therapies.ConclusionMetformin treatment was not associated with cancer-related mortality in adults compared with placebo or no treatment. However, metformin implied beneficial effects in the PFS of the patients with reproductive system cancers but was related to a worse PFS in digestive system cancers.Systematic review registrationPROSPERO registration number CRD42022324672.