scholarly journals A retrospective study on the role of diabetes and metformin in colorectal cancer disease survival

2016 ◽  
Vol 23 (2) ◽  
pp. 116 ◽  
Author(s):  
R. Ramjeesingh ◽  
C. Orr ◽  
C.S. Bricks ◽  
W.M. Hopman ◽  
N. Hammad

Background Recent studies have suggested an effect of metformin on mortality for patients with both diabetes and colorectal cancer (crc). However, the literature is contradictory, with both positive and negative effects being identified. We set out to determine the effect of metformin with respect to prognosis in crc patients.Methods After a retrospective chart review of crc patients treated at the Cancer Centre of Southeastern Ontario, Kaplan–Meier analyses and Cox proportional hazards regression models were used to compare overall survival (os) in patients with and without diabetes.Results We identified 1304 crc patients treated at the centre. No significant differences between the diabetic and nondiabetic groups were observed with respect to tumour pathology, extent of metastatic disease, time or toxicity of chemotherapy, and the os rate (1-year os: 85.6% vs. 86.4%, p = 0.695; 2-year os: 73.6% vs. 77.0%, p = 0.265). In subgroup analysis, diabetic patients taking metformin survived significantly longer than their counterparts taking other diabetes treatments (os for the metformin group: 91% at 1 year; 80.5% at 2 years; os for the group taking other treatments, including diet control: 80.6% at 1 year, 67.4% at 2 years). Multivariate analysis suggests that patients with diabetes taking treatments other than metformin experience worse survival (p = 0.025).Conclusions Our results suggest that crc patients with diabetes, excluding those taking metformin, might have a worse crc prognosis. Taking metformin appears to have a positive association with prognosis. The protective nature of metformin needs further evaluation in prospective analyses.

2016 ◽  
Vol 23 (6) ◽  
pp. 583 ◽  
Author(s):  
C. Graham ◽  
C. Orr ◽  
C.S. Bricks ◽  
W.M. Hopman ◽  
N. Hammad ◽  
...  

BackgroundProton pump inhibitors (ppis) are a commonly used medication. A limited number of studies have identified a weak-to-moderate association between ppi use and colorectal cancer (crc) risk, but none to date have identified an effect of ppi use on crc survival. We therefore postulated that an association between ppi use and crc survival might potentially exist.Methods We performed a retrospective chart review of 1304 crc patients diagnosed from January 2005 to December 2011 and treated at the Cancer Centre of Southeastern Ontario. Kaplan–Meier analysis and Cox proportional hazards regression models were used to evaluate overall survival (os).Results We identified 117 patients (9.0%) who were taking ppis at the time of oncology consult. Those taking a ppi were also more often taking asa or statins (or both) and had a statistically significantly increased rate of cardiac disease. No identifiable difference in tumour characteristics was evident in the two groups, including tumour location, differentiation, lymph node status, and stage. Univariate analysis identified a statistically nonsignificant difference in survival, with those taking a ppi experiencing lesser 1-year (82.1% vs. 86.7%, p = 0.161), 2-year (70.1% vs. 76.8%, p = 0.111), and 5-year os (55.2% vs. 62.9%, p = 0.165). When controlling for patient demographics and tumour characteristics, multivariate Cox regression analysis identified a statistically significant effect of ppi in our patient population (hazard ratio: 1.343; 95% confidence interval: 1.011 to 1.785; p = 0.042).Conclusions Our results suggest a potential adverse effect of ppi use on os in crc patients. These results need further evaluation in prospective analyses.


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 409-409
Author(s):  
Manasi S Shah ◽  
David R. Fogelman ◽  
Carrie Daniel-MacDougall ◽  
Kanwal Pratap Singh Raghav ◽  
John Heymach ◽  
...  

409 Background: Cancer-associated inflammation has been identified as a key determinant of disease progression and survival in colorectal cancer. We investigated the association between circulating inflammatory cytokines and survival in metastatic colorectal cancer (mCRC) patients. Methods: Plasma levels of 47 cytokines were measured using multiplex-bead assays in a cohort of 168 previously untreated mCRC patients. Demographic, clinical-pathological features, body mass index, and mortality data were abstracted from patient medical records. Overall survival (OS) was evaluated by Kaplan-Meier analysis and Cox proportional hazards regression. Results: Using principal component analysis, we identified a subset of cytokines explaining the maximum variance in OS; and found interleukin (IL)-1b, IL-5, IL-8, IL-12 and VEGF to be significantly associated with OS. However, only IL-8 was significantly and independently associated with OS in multivariable-adjusted models. For each 100 pg/ml increase in the level of circulating IL-8, hazard rate for death increased by 1.6 (95% CI 1.24-1.97). IL-8 measurements ranged from <1 to 413 pg/ml with a median value of 22 pg/ml. Median uncensored survival was 26.5 and 15.5 months among patients with IL-8 levels below and above this value, respectively. ROC analysis of IL-8 demonstrated an AUC of 0.69 (95% CI 0.60-0.76), as compared to 0.52 for CEA (95% CI 0.46-0.59). Conclusions: We identified an association between IL-8 and OS in previously untreated mCRC patients, suggesting its potential role as a prognostic inflammatory biomarker. In this dataset, IL-8 outperformed CEA as a prognostic biomarker, a finding which requires validation in subsequent work. Appropriately identifying, monitoring and managing chronic inflammation and the host inflammatory response during colorectal cancer treatment may be important for improving long-term survival.


2016 ◽  
Vol 30 (2) ◽  
pp. 185-194 ◽  
Author(s):  
George K. Nimako ◽  
Zachary A. P. Wintrob ◽  
Dmitriy A. Sulik ◽  
Jennifer L. Donato ◽  
Alice C. Ceacareanu

Objectives: To evaluate whether statin use influences gastrointestinal cancer prognosis in patients with diabetes mellitus (DM). Methods: We reviewed all DM patients diagnosed at Roswell Park Cancer Institute with emergent gastrointestinal malignancy (January 2003 to December 2010) (N = 222). Baseline demographic, clinical history, and cancer outcomes were documented. Overall survival (OS) and disease-free survival (DFS) comparisons across various treatment groups were assessed by Kaplan-Meier and Cox proportional hazards. Results: Use of statin, alone or in combination, was associated with improved OS and DFS (hazard ratio [HR] = 0.65, P = .06; HR = 0.60, P < .02). We report similar OS and DFS advantage among users of mono- or combined metformin therapy (HR = 0.55, P < .01; HR = 0.63, P < .02). Concomitant use of metformin and statin provided a synergistic OS and DFS benefit (HR = 0.42, P < .01; HR = 0.44, P < .01). Despite significant tobacco and alcohol use history, patients with upper gastrointestinal cancers derived enhanced cancer outcomes from this combination (HR = 0.34, P < .01; HR = 0.43, P < .02), while receiving a statin without metformin or metformin without a statin did not provide significant cancer-related benefits. Conclusion: Use of statin and metformin provides a synergistic improvement in gastrointestinal malignancies outcomes.


2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S201-S202
Author(s):  
M Kabir ◽  
K Curtius ◽  
P Kalia ◽  
I Al Bakir ◽  
C H R Choi ◽  
...  

Abstract Background Racial disparities in inflammatory bowel disease (IBD) phenotypic presentations and outcomes are recognised. However, there are conflicting data from Western population-based cohort studies as to whether racial differences in colitis-associated colorectal cancer (CRC) incidence exists. To our knowledge this is the first study to investigate the impact of ethnicity on the natural history of dysplasia in ulcerative colitis (UC). Methods We performed a retrospective multi-centre cohort study of adult patients with UC whose first low-grade dysplasia (LGD) diagnosis within the extent of colitis was made between 1 January 2001 and 30 December 2018. Only patients with at least one follow-up colonoscopy or colectomy by 30 August 2019 were included. The study end point was time to CRC or end of follow-up. Statistical differences between groups were evaluated using Mann-Whitney U tests and Chi-squared tests. Survival analyses were performed using Kaplan-Meier estimation and multivariate Cox proportional hazards models. Results 408 patients met the inclusion criteria (see Figure 1 for patient and clinical demographics). More patients from a Black or Asian (BAME) background progressed to CRC [13.4% vs. 6.4%; p=0.036] compared to their White Caucasian counterparts, despite having surveillance follow-up. Figure 2 displays Kaplan-Meier curves demonstrating the probability of remaining CRC-free after LGD diagnosis and categorised by ethnicity. BAME patients were more likely to have moderate-severe inflammatory activity on colonic biopsy within the 5 preceding years [42.0% vs. 28.9%; p=0.023], but no significant differences in medication use and a longer median time interval from LGD diagnosis to colectomy date [32 months vs. 11 months; p=0.021]. After adjusting for sex, age and UC duration at time of LGD diagnosis and presence of moderate-severe histological inflammation, being Black or Asian was a predictive factor for CRC progression on multivariate Cox proportional hazard analysis [HR 2.97 (95% CI 1.22 – 7.20); p = 0.016]. However, ethnicity was no longer predictive of CRC progression on sub-analysis of the 317 patients who did not have a colectomy during the follow-up period. Conclusion In this UK multi-centre cohort of UC surveillance patients diagnosed with LGD, delays in receiving cancer preventative colectomy may contribute to an increased CRC incidence in certain ethnic groups. Further work is required to elucidate whether these delays are related to institutional factors (e.g. inequity in the content of decision-making support given or access to healthcare) or cultural factors.


10.2196/15911 ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. e15911
Author(s):  
Ahmed Abdulaal ◽  
Chanpreet Arhi ◽  
Paul Ziprin

Background The United Kingdom has lower survival figures for all types of cancers compared to many European countries despite similar national expenditures on health. This discrepancy may be linked to long diagnostic and treatment delays. Objective The aim of this study was to determine whether delays experienced by patients with colorectal cancer (CRC) affect their survival. Methods This observational study utilized the Somerset Cancer Register to identify patients with CRC who were diagnosed on the basis of positive histology findings. The effects of diagnostic and treatment delays and their subdivisions on outcomes were investigated using Cox proportional hazards regression. Kaplan-Meier plots were used to illustrate group differences. Results A total of 648 patients (375 males, 57.9% males) were included in this study. We found that neither diagnostic delay nor treatment delay had an effect on the overall survival in patients with CRC (χ23=1.5, P=.68; χ23=0.6, P=.90, respectively). Similarly, treatment delays did not affect the outcomes in patients with CRC (χ23=5.5, P=.14). The initial Cox regression analysis showed that patients with CRC who had short diagnostic delays were less likely to die than those experiencing long delays (hazard ratio 0.165, 95% CI 0.044-0.616; P=.007). However, this result was nonsignificant following sensitivity analysis. Conclusions Diagnostic and treatment delays had no effect on the survival of this cohort of patients with CRC. The utility of the 2-week wait referral system is therefore questioned. Timely screening with subsequent early referral and access to diagnostics may have a more beneficial effect.


2019 ◽  
Author(s):  
Ahmed Abdulaal ◽  
Chanpreet Arhi ◽  
Paul Ziprin

BACKGROUND The United Kingdom has lower survival figures for all types of cancers compared to many European countries despite similar national expenditures on health. This discrepancy may be linked to long diagnostic and treatment delays. OBJECTIVE The aim of this study was to determine whether delays experienced by patients with colorectal cancer (CRC) affect their survival. METHODS This observational study utilized the Somerset Cancer Register to identify patients with CRC who were diagnosed on the basis of positive histology findings. The effects of diagnostic and treatment delays and their subdivisions on outcomes were investigated using Cox proportional hazards regression. Kaplan-Meier plots were used to illustrate group differences. RESULTS A total of 648 patients (375 males, 57.9% males) were included in this study. We found that neither diagnostic delay nor treatment delay had an effect on the overall survival in patients with CRC (χ<sup>2</sup><sub>3</sub>=1.5, <i>P</i>=.68; χ23=0.6, <i>P</i>=.90, respectively). Similarly, treatment delays did not affect the outcomes in patients with CRC (χ<sup>2</sup><sub>3</sub>=5.5, <i>P</i>=.14). The initial Cox regression analysis showed that patients with CRC who had short diagnostic delays were less likely to die than those experiencing long delays (hazard ratio 0.165, 95% CI 0.044-0.616; <i>P</i>=.007). However, this result was nonsignificant following sensitivity analysis. CONCLUSIONS Diagnostic and treatment delays had no effect on the survival of this cohort of patients with CRC. The utility of the 2-week wait referral system is therefore questioned. Timely screening with subsequent early referral and access to diagnostics may have a more beneficial effect.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1593-1593
Author(s):  
Ravi Ramjeesingh ◽  
Christine Orr ◽  
Lyndsay Richardson ◽  
Nazik Hammad

1593 Background: Recent studies have suggested a potential epidemiological role for diabetes as an independent risk factor for the development of colorectal cancer (CRC). These studies have furthermore suggested patients with diabetes who develop colorectal cancer have an increased mortality. Methods: To identify a potential correlation between CRC and diabetes, we are performing a retrospective chart review of CRC patients treated at the Cancer Center of Southeastern Ontario diagnosed from January 2005 to December 2011. 1,300 colorectal cancer patient charts have been identified through Ontario Cancer Registry Data based on confirmed ICD-10 diagnosis codes and the variables of 200 random patients have been extracted into our database thus far. The final analysis will be completed April 2013. Results: Preliminary analysis of the database has indicated that the average age of patients with CRC was 69 years with 55% being women. The incidence of diabetes in our CRC population was 19%, double the rate of diabetes in the general population in Canada. As expected, the rate of co-morbidities excluding diabetes was higher in the diabetic group (92.9% vs 69.3%; p=0.004). When we looked at the diabetic population specifically, the rate of death was not significantly different compared to the non-diabetic population (13.2% vs 12.7%, p=0.94), however those with diabetes presented with later-stage (stage 2/3/4) disease (92.1% versus 88.6%). The average number of days from the time of diagnosis to death in the diabetic group (200 days) was half compared to the non-diabetic group (420 days, p=0.014). However, there was no statistical difference in the percentage of progression, number of different metastatic sites or the burden of metastatic disease amongst the two populations. A subgroup analysis of diabetic patients on metformin illustrated that the death rate (p=0.06), rate of progression (33% vs 20%) and those presenting with later stage disease was higher in patients not on metformin compared to those on the drug. Conclusions: Our preliminary work suggests diabetics with CRC may have a worst prognosis however taking metformin may have a positive impact on prognosis.


1996 ◽  
Vol 16 (1_suppl) ◽  
pp. 283-288 ◽  
Author(s):  
Daniele Marcelli ◽  
Donatella Spotti ◽  
Ferruccio Conte ◽  
Alfonso Tagliaferro ◽  
Aurelio Limido ◽  
...  

Our objective was to analyze the survival of diabetic patients on renal replacement therapy and to compare their survival on extracorporeal and on peritoneal dialysis. All data regarding diabetic patients admitted to dialysis between 1 January 1983 and 31 December 1993 were collected by means of individual patient questionnaires sent to all of the 44 regional Renal Units (100% answers) of Lombardy, Italy. Cox proportional hazards model, stepwise procedure, was applied in order to select the covariates significantly associated with survival. Age (at baseline), sex, type of diabetes, initial modality of treatment (hemodialysis or peritoneal dialysis), and initial clinical risk factors (malignancies, serious heart disease, vascular disease, cirrhosis of the liver, cachexia) were considered. Descriptive analysis of survival was performed using the Kaplan-Meier technique. The survival of all diabetic patients (895) was 86.5% at one year, 52% at three years, an d 34% at five years. The main causes of the 488 deaths of diabetic patients were cardiovascular diseases (56%), cachexia (18%), and infections (11%). The relative death risk of patients on peritoneal dialysis versus those on hemodialysis, after taking into account the main comorbid conditions, did not significantly differ from 1, as estimated by the Cox proportional hazards regression model. Five-year survival of diabetic patients was 34%, and no differences were found between peritoneal dialysis and hemodialysis as far as mortality is concerned.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Robert J Mentz ◽  
Adam Z Banks ◽  
Samuel Broderick ◽  
Adam D DeVore ◽  
Karen Chiswell ◽  
...  

Background: Angina pectoris (AP) has different prognostic implications in various populations. Patients with diabetes mellitus (DM) may experience neuropathy such that AP may not be perceived in the setting of coronary artery disease (CAD). The association between the presence or absence of AP in DM patients with CAD is unknown. Methods: We analyzed DM patients with obstructive CAD who underwent coronary angiography at Duke University Medical Center from 2002 to 2011 and compared patients without AP to those with AP. DM and AP were defined based on physician-obtained past medical history at catheterization. Patients were categorized as no AP, atypical AP or typical AP within the 6 weeks prior. We assessed the association with subsequent cardiovascular (CV) death/CV hospitalization and all-cause mortality in patients with no or atypical AP relative to typical AP using multivariable Cox proportional hazards analysis. Results: In the Duke Databank, 5550 patients met criteria for inclusion and 1732 (31%) had no AP, 1075 (19%) had atypical AP and 2743 (50%) had typical AP. Those without AP more often had a prior MI and lower ejection fraction, but had similar HbA1c values compared to those with atypical AP or typical AP. Over a median follow-up of 5.4 years (IQR: 2.9-8.8), the lack of recent AP was associated with increased risk for outcomes (Table). Following adjustment, the lack of recent AP was independently associated with increased mortality compared to typical AP. Conclusions: In DM patients with CAD, the lack of AP was associated with increased mortality, but similar risk for CV events compared to patients with typical AP. Future studies are needed to assess whether these findings are related to increased severity of disease in those without AP or whether AP leads to differential management that improves survival.


2013 ◽  
Vol 79 (1) ◽  
pp. 35-39 ◽  
Author(s):  
Robert M. Cannon ◽  
Russell E. Brown ◽  
Charles R. Hill ◽  
Eric Dunki-Jacobs ◽  
Robert C. G. Martin ◽  
...  

There has been conflicting evidence regarding negative effects of blood transfusion in oncology patients. This study was undertaken to determine any negative effects of specific blood product transfusion after resection of hepatic colorectal metastases (CRM). Retrospective review of patients undergoing hepatectomy for CRM from 1995 to 2009 at a single institution was performed. Specific attention was paid to the effect of blood transfusion within 30 days of operation on overall survival, disease-free survival (DFS), and complications. To mitigate the bias introduced by complications that require blood transfusion to treat, only nonbleeding complications were considered. Complications were analyzed with univariate and multivariate logistic regression. Survival was analyzed according to Kaplan-Meier and Cox proportional hazards. There were 239 patients included in the study. There were 64 (26.8%) receiving a transfusion of any kind with 25.5 per cent getting red cells (PRBCs), 7.11 per cent getting fresh-frozen plasma, and 3.77 per cent getting platelets. Multivariate analysis revealed only PRBC transfusion to be independently associated with nonbleeding complications (odds ratio, 1.980; 95% confidence interval, 1.094 to 3.582; P = 0.0239). There was no significant adverse effect of transfusion with any product on overall or DFS. PRBC transfusion appears to increase the risk of postoperative complications; thus, strategies to minimize blood use may be warranted.


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