Colorectal Cancer Outcomes,Recurrence, and Complications in Persons With and Without Diabetes Mellitus: A Systematic Review and Meta-Analysis

Background  

Diabetes mellitus increases the risk of incident colorectal cancer, but it is less clear if pre-existing diabetes mellitus influences mortality outcomes, recurrence risk, and/or treatment-related complications in persons with colorectal cancer.     

Intensive glycaemic control and cancer risk in type 2 diabetes: a meta-analysis of major trials

Aims/hypothesis  

The purpose of this study was to explore the relationship between hyperglycaemia in type 2 diabetes and risk of cancer incidence or cancer mortality. We were interested to determine if data from major randomised controlled trials would support a hypothesis that improving glycaemic control may reduce the risk of cancer outcomes.     

Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials

Aims/hypothesis  

Observational studies suggest that metformin may reduce cancer risk by approximately one-third. We examined cancer outcomes and all-cause mortality in published randomised controlled trials (RCTs).     

The metabolic syndrome and its components as prognostic factors in colorectal cancer: A meta-analysis and systematic review

Background and Aim

Metabolic syndrome (MetS) increases the risk of colorectal cancer (CRC), and the impact of MetS on CRC prognosis remains controversial after the diagnosis of CRC has been established. This study aimed to explore the impact of the individual components and synergies of MetS on the prognosis of patients with CRC.

Methods

We searched articles published before August 3, 2022, in four databases, including PubMed, Embase, Cochrane Library, and ScienceDirect. The random-effects model inverse variance method was used to estimate the summarized effect size.

Results

Patients with CRC with MetS were 1.342 times more likely to experience all-cause mortality than those without MetS, and the 95% confidence interval (CI) of hazard ratio (HR) was 1.107–1.627 (P = 0.003). CRC-specific mortality in patients with CRC with MetS was 2.122 times higher than in those without MetS, and the 95% CI of HR was 1.080–4.173 (P = 0.029). CRC-specific mortality exhibited an increasing trend of risk with increased metabolic risk factors. The HR of CRC-specific mortality for one, two, and three metabolic risk factors was 1.206 (95% CI, 1.034–1.407; P = 0.017), 1.881 (95% CI, 1.253–2.824; P = 0.002), and 2.327 (95% CI, 1.262–4.291; P = 0.007), respectively.

Conclusions

Metabolic syndrome increased all-cause and CRC-specific mortality in patients with CRC. As a single component of MetS, diabetes mellitus increased overall mortality in patients with CRC, while obesity increased CRC-specific mortality in patients with CRC, with a significant difference from non-MetS. Moreover, the risk of CRC-specific mortality increased with increasing number of metabolic risk factors.     

Impact of obesity on surgical and oncological outcomes in the management of colorectal cancer

Introduction  

Obesity is an established risk factor for colorectal cancer, particularly in males, and may negatively impact on oncologic outcomes. The aim of this study was to examine the impact of body mass index (BMI) on mortality and morbidity, tumour pathology, and overall survival in a consecutive cohort of Irish colorectal cancer patients treated with curative intent.     

Higher Physician Density is Associated with Lower Incidence of Late-stage Colorectal Cancer

INTRODUCTION  

Colorectal cancer (CRC) is the third most common cancer in the United States and a leading cause of cancer related mortality. Routine screening decreases incidence and mortality; however rates of screening remain low. Physician recommendation is a key determinant of screening rates; thus, physician availability may also influence CRC incidence and mortality.     

Soluble tumor necrosis factor receptor 1 (sTNFR1) is associated with increased total mortality due to cancer and cardiovascular causes – Findings from two community based cohorts of elderly

Background

Experimental evidence support soluble receptors for tumor necrosis factor alpha as important mediators of the underlying pathology leading to cardiovascular disease and cancer. However, prospective data concerning the relation between circulating soluble tumor necrosis factor receptor-1 (sTNFR1) and mortality in humans are lacking. We aimed to explore and validate the association between sTNFR1 and mortality, and to explore the influence of other established risk factors for mortality, including other inflammatory markers.

Methods

The association between serum sTNFR1and the risk for mortality was investigated in two community-based cohorts of elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n = 1005, mean age 70 years, median follow-up 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 775, mean age 77 years, median follow-up 8.1 years).

Results

In total, 101 participants in PIVUS and 274 in ULSAM died during follow-up. In multivariable Cox regression models adjusted for inflammation, lifestyle and established cardiovascular risk factors, one standard deviation (SD) higher sTNFR1 was associated with a hazard ratio (HR) for mortality of 1.37, 95% confidence interval (CI) 1.17–1.60, in PIVUS and HR 1.22, 95% CI 1.10–1.37 in ULSAM. Moreover, circulatingsTNFR1 was associated with cardiovascular mortality (HR per SD of sTNFR1, 1.24, 95% CI 1.07–1.44) and cancer mortality (HR per SD of sTNFR1, 1.32, 95% CI 1.11–1.57) in the ULSAM cohort. High levels of sTNFR1 identified individuals with increased risk of mortality among those with high as well as low levels of systemic inflammation.

Conclusions

An association between circulating sTNFR1 and an increased risk for mortality was found and validated in two independent community-based cohorts. The future clinical role of sTNFR1 to identify high risk patients for adverse outcomes and mortality has yet to be determined.     

Oestradiol level,oestrogen receptors,and mortality in elderly men: The three‐city cohort study

Context

Although endogenous oestradiol, generally considered as the female hormone, has been little investigated in men, it could play a role in men's health, mortality in particular. The influence of oestrogen receptors (ER) genetic polymorphisms on this relationship has never been studied.

Design and Participants

The Three‐City cohort study included (1999‐2001) 3650 men ≥65 years who were followed for mortality over 12 years. At baseline, total oestradiol (tE2) was measured and ER genotyped in a random subsample of 472 men without hormonal treatment. Free oestradiol (fE2) was estimated using Vermeulen and Södergard algorithms.

Main Outcome

Mortality data were obtained from death certificates. We used inverse probability weighted Cox models to examine the association of oestradiol with all‐cause and cause‐specific mortality and its interaction with ER genetic polymorphisms.

Results

A total of 183 men died over the follow‐up (cardiovascular disease (CVD), n = 44; cancer, n = 57; other causes, n = 82). After adjustment, there was a quadratic relationship of all‐cause mortality with tE2 and fE2 (P‐quadratic = 0.04 and 0.05, respectively), with higher mortality for the top and bottom tertiles compared to the middle one. These associations were stronger for CVD mortality (P‐quadratic = 0.01 and 0.02 for tE2 and fE2, respectively) and disappeared for cancer mortality. There was no evidence of an interaction of oestradiol with any ER polymorphisms on all‐cause mortality.

Conclusion

In elderly men, we showed a nonlinear association of tE2 and fE2 with all‐cause mortality. These quadratic relationships were stronger for CVD mortality and did not exist for cancer mortality. ER genetic polymorphisms did not modify this association.     

No evidence of an increased mortality risk associated with low levels of glycated haemoglobin in a non-diabetic UK population

Aims/hypothesis  

There is debate about increased mortality risk associated with low levels of glycaemia. To address this issue, we examined the shape of the risk relationship between glycated haemoglobin and mortality in a UK population.     

Social participation and incident disability and mortality among frail older adults: A JAGES longitudinal study

Background

Frailty is the highest risk factor for incident disability and mortality. Social participation is a modifiable factor for reducing adverse outcomes among independent older adults. However, the association between social participation and incident disability and mortality among frail older adults remains unclear. Therefore, we examined the association between various social activities and incident disability and mortality.

Methods

This nationwide prospective cohort study (The Japan Gerontological Evaluation Study) recruited older adults with frailty, aged 65 years and older (N = 9090) who were followed up for 6 years (2010–2016). We examined incident disability and all-cause mortality at the end of the follow-up period. Frailty was assessed using the Kihon Checklist. The independent variable was social participation in 2010, grouped into the following seven categories: hobby groups, sports groups or clubs, volunteer groups, senior citizens' clubs, industries, neighborhood communities, and paid work.

Results

The incidence of disability among participants was 19.5% (1770) and that of mortality was 19.2% (1753). Belonging to sports groups or clubs (Hazard Ratios [HR] = 0.74; 95% Confidence Interval [CI] = 0.57, 0.98) or hobby groups (HR = 0.77; 95% CI = 0.60, 0.98) was significantly associated with a lower risk of incident disability. Meanwhile, hobby groups (HR = 0.68; 95% CI = 0.56, 0.83), sports groups or clubs (HR = 0.71; 95% CI = 0.57, 0.88), volunteer groups (HR = 0.69; 95% CI = 0.54, 0.88), and senior citizens' club (HR = 0.75; 95% CI = 0.61, 0.90) were associated with lower risk of incident mortality.

Conclusions

Social participation was associated with a lower risk of incident disability and mortality, not only in healthy older adults but also in frail older adults who are at higher risk of incident disability and mortality. This suggests that frail older adults should be encouraged to participate in all the seven types of social participation examined in this study, as this may lower the risk of subsequent disability and mortality.     

Cancer-Specific Mortality in Chronic Kidney Disease: Longitudinal Follow-Up of a Large Cohort

Summary

Background and objectives

Chronic kidney disease (CKD) is known to be associated with increased all-cause and cardiovascular mortality, but no large studies examined the cancer-specific mortality in non–dialysis-dependent CKD patients. Such outcome data are needed for proper allocation of resources and would help to develop better preventive services.

Design, setting, participants, & measurements

Between 1998 and 1999, 123,717 adults were recruited from four health screening centers in Taiwan. The estimated glomerular filtration rate was calculated using the four-variable Modification of Diet in Renal Disease Study equation for the Chinese. Mortality was ascertained by computer linkage to the national death registry after a median follow-up of 7.06 years. Cox proportional hazards regression models were used to estimate the impact of CKD on cancer-specific mortality.

Results

A higher risk for overall cancer mortality was found in CKD patients compared with non-CKD patients (adjusted hazard ratio, 1.2). CKD was associated with increased mortality from liver cancer, kidney cancer, and urinary tract cancer, with an adjusted hazard ratio of 1.74, 3.3, and 7.3, respectively. A graded relationship between the severity of renal impairment and cancer mortality was also found.

Conclusions

Patients with CKD had a higher mortality risk of liver cancer, kidney cancer, and urinary tract cancer. This is the first large study that showed an inverse association between renal function and liver cancer mortality. The increased mortality could be caused by higher cancer incidence or worse response to cancer treatment. Future research is warranted to clarify the mechanism.     

Elevated ALT and GGT predict all-cause mortality and hepatocellular carcinoma in Taiwanese male: a case-cohort study

Purpose

Evidence indicates a positive association between liver enzymes and the risk of death in Western countries; however, the evidence in Asian populations is scarce. We investigated the association between liver enzymes and total, cardiovascular (CVD), cancer and hepatocellular carcinoma (HCC) mortality in a cohort of Taiwanese male free of cancer at baseline.

Methods

From 1996 to 2003, 54,751 Taiwanese male aged 40–80 years without cancer completed a health screening and were followed through 2005 (5.8 ± 2.5 years of follow-up). A random cohort of 3,961 male was selected to compare to 1,864 male who died. We used Cox proportional hazards regression models to assess the risk of all-cause, cardiovascular and cancer mortality associated with alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transferase (GGT).

Results

In this population, higher levels of ALT, AST and GGT were significantly associated with all-cause mortality [hazard ratio (HR) 1.2, 1.8 and 1.6 for ALT, AST and GGT, respectively; all p < 0.05], cancer mortality (HR 1.8–2.8) and HCC mortality (HR 5.5–36.1). GGT was significantly associated with CVD mortality (HR 1.2).

Conclusions

In Taiwanese male free of cancer at baseline, elevations of ALT, AST and GGT were associated with future risk of all-cause death, all cancer and HCC mortality, independent of conventional risk factors, and could be used to identify male who would benefit from HCC screening.     

Impact of Comorbidity on Mortality Among Older Persons with Advanced Heart Failure

BACKGROUND  

Care for patients with advanced heart failure (HF) has traditionally focused on managing HF alone; however, little is known about the prevalence and contribution of comorbidity to mortality among this population. We compared the impact of comorbidity on mortality in older adults with HF with high mortality risk and those with lower mortality risk, as defined by presence or absence of a prior hospitalization for HF, respectively.     

Proteomics analysis of serum protein profiling in pancreatic cancer patients by DIGE: up-regulation of mannose-binding lectin 2 and myosin light chain kinase 2

Background  

Pancreatic cancer has significant morbidity and mortality worldwide. Good prognosis relies on an early diagnosis. The purpose of this study was to develop techniques for identifying cancer biomarkers in the serum of patients with pancreatic cancer.     

Preoperative anaemia and perioperative red blood cell transfusion as prognostic factors for recurrence and mortality in colorectal cancer—a Swedish cohort study

Purpose

The hypothesis in this study was that anaemia prior to surgery and perioperative red blood cell transfusion increases the risk for recurrence and overall mortality in patients with stages I–III colorectal cancer after abdominal resection with curative intent.

Methods

This is a Swedish single centre retrospective cohort study. Data on 496 consecutive radical abdominal resections stages I–III colorectal cancer performed at the Karolinska University Hospital 2007–2010 were extracted from the Swedish Colorectal Cancer Registry. Data were linked to local laboratory and transfusion databases to identify preoperative anaemia and perioperative transfusion. Disease recurrence was validated by scrutiny of patient records. A total of 496 stages I–III colorectal cancer patients were included in the analysis. Multivariate Cox regression analysis adjusted for tumour and patient characteristics were performed to assess risk for recurrence and overall mortality.

Results

Anaemia prior to surgery was associated with increased risk for overall mortality (HR 2.1, 95% CI 1.4–3.2). There was no association between anaemia and risk for recurrence (HR 1.6, 95% CI 0.97–2.6). Transfusion was not associated with increased risk of recurrence (HR 0.7, 95% CI 0.4–1.3) or overall mortality (HR 1.04, 95% CI 0.7–1.6).

Conclusions

Anaemia prior to colorectal cancer surgery was associated with increased risk for overall mortality while a no increased risk was seen for recurrence. Previous findings indicating an association between blood transfusion and increased risk for recurrence could not be confirmed.

     

The impact of buprenorphine and methadone on mortality: a primary care cohort study in the United Kingdom

Aims

To estimate whether opioid substitution treatment (OST) with buprenorphine or methadone is associated with a greater reduction in the risk of all‐cause mortality (ACM) and opioid drug‐related poisoning (DRP) mortality.

Design

Cohort study with linkage between clinical records from Clinical Practice Research Datalink and mortality register.

Setting

UK primary care.

Participants

A total of 11 033 opioid‐dependent patients who received OST from 1998 to 2014, followed‐up for 30 410 person‐years.

Measurements

Exposure to methadone (17 373, 61%) OST episodes or buprenorphine (9173, 39%) OST episodes. ACM was available for all patients; information on cause of death and DRP was available for 5935 patients (54%) followed‐up for 16 363 person‐years. Poisson regression modelled mortality by treatment period with an interaction between OST type and treatment period (first 4 weeks on OST, rest of time off OST, first 4 weeks off OST, rest of time out of OST censored at 12 months) to test whether ACM or DRP differed between methadone and buprenorphine. Inverse probability weights were included to adjust for confounding and balance characteristics of patients prescribed methadone or buprenorphine.

Findings

ACM and DRP rates were 1.93 and 0.53 per 100 person‐years, respectively. DRP was elevated during the first 4 weeks of OST [incidence rate ratio (IRR) = 1.93 95% confidence interval (CI) = 0.97–3.82], the first 4 weeks off OST (IRR = 8.15, 95% CI = 5.45–12.19) and the rest of time out of OST (IRR = 2.13, 95% CI = 1.47–3.09) compared with mortality risk from 4 weeks to end of treatment. Patients on buprenorphine compared with methadone had lower ACM rates in each treatment period. After adjustment, there was evidence of a lower DRP risk for patients on buprenorphine compared with methadone at treatment initiation (IRR = 0.08, 95% CI = 0.01–0.48) and rest of time on treatment (IRR = 0.37, 95% CI = 0.17–0.79). Treatment duration (mean and median) was shorter on buprenorphine than methadone (173 and 40 versus 363 and 111, respectively). Model estimates suggest that there was a low probability that methadone or buprenorphine reduced the number of DRP in the population: 28 and 21%, respectively.

Conclusions

In UK general medical practice, opioid substitution treatment with buprenorphine is associated with a lower risk of all‐cause and drug‐related poisoning mortality than methadone. In the population, buprenorphine is unlikely to give greater overall protection because of the relatively shorter duration of treatment.     

Patient Navigation to Increase Mammography Screening Among Inner City Women

Background  

Lower mammography screening rates among minority and low income women contribute to increased morbidity and mortality from breast cancer.     

Inhibitory effect of cucurbitacin E on pancreatic cancer cells growth via STAT3 signaling

Purpose  

Pancreatic cancer has been a serious disease worldwide for its high mortality. Cucurbitacin E is a member of triterpenoid family isolated from plants showing antiproliferative activity on various cancer cells. In this study, we have explored whether cucurbitacin E also has an anti-tumor effect on pancreatic cancer cells.     

Glucose-lowering agents and the patterns of risk for cancer: a study with the General Practice Research Database and secondary care data

Introduction  

Recent studies suggesting an increased cancer risk with glucose-lowering agents have received widespread publicity. The objectives of this study were to evaluate the comparability in underlying cancer risk and patterns of cancer risk over time with different glucose-lowering agents.     

Effect of Including Cancer Mortality on the Cost-Effectiveness of Aspirin for Primary Prevention in Men

BACKGROUND

Recent data suggest that aspirin may be effective for reducing cancer mortality.

OBJECTIVE

To examine whether including a cancer mortality-reducing effect influences which men would benefit from aspirin for primary prevention.

DESIGN

We modified our existing Markov model that examines the effects of aspirin among middle-aged men with no previous history of cardiovascular disease or diabetes. For our base case scenario of 45-year-old men, we examined costs and life-years for men taking aspirin for 10 years compared with men who were not taking aspirin over those 10 years; after 10 years, we equalized treatment and followed the cohort until death. We compared our results depending on whether or not we included a 22 % relative reduction in cancer mortality, based on a recent meta-analysis. We discounted costs and benefits at 3 % and employed a third party payer perspective.

MAIN MEASURE

Cost per quality-adjusted life year (QALY) gained.

KEY RESULTS

When no effect on cancer mortality was included, aspirin had a cost per QALY gained of $22,492 at 5 % 10-year coronary heart disease (CHD) risk; at 2.5 % risk or below, no treatment was favored. When we included a reduction in cancer mortality, aspirin became cost-effective for men at 2.5 % risk as well (cost per QALY, $43,342). Results were somewhat sensitive to utility of taking aspirin daily; risk of death after myocardial infarction; and effects of aspirin on stroke, myocardial infarction, and sudden death. However, aspirin remained cost-saving or cost-effective (< $50,000 per QALY) in probabilistic analyses (59 % with no cancer effect included; 96 % with cancer effect) for men at 5 % risk.

CONCLUSIONS

Including an effect of aspirin on cancer mortality influences the threshold for prescribing aspirin for primary prevention in men. If such an effect is real, many middle-aged men at low cardiovascular risk would become candidates for regular aspirin use.