Genetic variants involved in the lipid metabolism pathway to predict outcome in patients (pts) with metastatic colorectal cancer (mCRC): Data from FIRE-3 and MAVERICC trials.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 118-118
Author(s):  
Jingyuan Wang ◽  
Joshua Millstein ◽  
Fotios Loupakis ◽  
Sebastian Stintzing ◽  
Hiroyuki Arai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lipid Metabolism ◽  
Genetic Variants ◽  
Progression Free Survival ◽  
Snp Markers ◽  
Acid Oxidation ◽  
Metabolism Pathway ◽  
Increased Risk ◽  
In Fire ◽  
The Impact

118 Background: Antiangiogenic drug (AAD)-triggered oxygen and nutrient depletion through suppression of angiogenesis switches the glucose-dependent metabolism to lipid-dependent metabolism. Blocking fatty acid oxidation can enhance AAD-mediated anti-tumor effects in colorectal cancer. Previous reports suggested that polymorphisms of the lipid metabolism-related genes are associated with the increased risk of CRC and poor clinical outcome in CRC. Therefore, we hypothesized that genetic variants in the lipid metabolism pathway may predict first-line treatment outcome in mCRC pts. Methods: Genomic DNA from blood samples of pts enrolled in two independent randomized trials, FIRE-3 and MAVERICC, was genotyped through the OncoArray, a customized array manufactured by Illumina including approximately 530K SNP markers. The impact on outcome of 25 selected SNPs in 10 genes involved in the lipid metabolism pathway (CD36, FABP4, LPCAT1, LPCAT2, PPARG, CPT1A, ACSS2, SREBF1, FASN, ACACA) was analyzed. Those treated with FOLFIRI/ bevacizumab (bev) in FIRE-3 (n = 107) and MAVERICC (n = 163) served as discovery and validation cohorts respectively, while FIRE-3 FOLFIRI/ cetuximab (cet) (n = 129) arm was used as the control. Interaction between each SNP and treatment was evaluated in FIRE-3 (FOLFIRI/bev arm vs. FOLFIRI/cet arm). Results: In the discovery (FIRE-3 bev) cohort, pts with FASN rs4485435 any C allele (N = 21) showed significantly shorter progression-free survival (PFS) (8.69 vs 13.48 months) compared to carriers of G/G (N = 62) in both univariate (hazard ratio [HR] = 2.88; 95% confidence interval [CI]: 1.57-5.29; p = 0.00037) and multivariate (HR = 2.87; 95%CI 1.4-5.9; p = 0.00675) analyses. These data were validated in the MAVERICC bev cohort in multivariate analysis (11.17 vs 14.06 months; HR = 2.07; 95%CI: 1.15-3.74; p = 0.02). Pts carrying any T allele in PPARG rs3856806 (N = 36) showed significantly longer overall survival (OS) (Not reached vs 42 months) than carriers of C/C (n = 93) in the FIRE-3 cet cohort in both univariate (HR = 0.4; 95%CI 0.17-0.92; p = 0.03) and multivariate (HR = 0.37; 95%CI 0.15-0.93; p = 0.02) analyses, but the association was not observed in the bev cohort of MAVERICC and FIRE-3. In the comparison of bev arm vs cet arm in FIRE-3, interactions were shown with FASN rs4485435 (p = 0.017) on PFS and PPARG rs3856806 (p = 0.059) on OS. Conclusions: Our study demonstrates for the first time that FASN polymorphism could predict outcomes of bev-based treatment in mCRC patients; Meanwhile PPARG polymorphism could predict outcomes of cet-based treatment in mCRC patients. These findings support a possible role of the lipid metabolism pathway in contributing to resistance to anti-VEGF/EGFR treatment.

Genetic variants involved in the cGAS-STING pathway to predict outcome in patients (pts) with metastatic colorectal cancer (mCRC): Data from FIRE-3 and TRIBE trials.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3535-3535
Author(s):  
Jingyuan Wang ◽  
Yi Xiao ◽  
Fotios Loupakis ◽  
Sebastian Stintzing ◽  
Hiroyuki Arai ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Cell Activation ◽  
Killer Cell ◽  
Progression Free Survival ◽  
Dendritic Cell Maturation ◽  
Vital Role ◽  
Snp Markers ◽  
Sting Pathway ◽  
The Impact ◽  
First Time

3535 Background: The intracellular DNA sensor stimulator of interferon genes (STING) plays a vital role in anti-tumor immune responses by recognition of self-DNA from tumors and by-products of genomic instability. Activation of STING was reported to enhance cetuximab mediated natural killer cell activation and dendritic cell maturation. Previous reports suggested that polymorphisms of cGAS-STING can affect innate immune response. Therefore, we hypothesized that genetic variants in the cGAS-STING pathway may predict first-line treatment outcome in mCRC pts treated with bevacizumab/cetuximab-based chemotherapy. Methods: Genomic DNA from blood samples of pts enrolled in two independent randomized trials, FIRE-3 (cetuximab arm, n = 129; bevacizumab arm, n = 107) and TRIBE (bevacizumab arm, n = 215), was genotyped through the OncoArray, a customized array manufactured by Illumina including approximately 530K SNP markers. The impact on outcome of 7 selected SNPs in 3 genes involved in the STING pathway (cGAS, STING, IFNB1) was analyzed. Results: In the Cetuximab cohort, pts with STING rs1131769 any T allele (N = 29) showed significantly shorter overall survival (36.3 vs 56.07 months) compared to carriers of C/C (N = 95) in both univariate (hazard ratio [HR] = 2.08; 95% confidence interval [CI]: 1.06-4.07; p = 0.003) and multivariate (HR = 2.98; 95%CI 1.35-6.6; p = 0.00848) analysis; Pts carrying IFNB1 rs1051922 any A allele (N = 68) showed significant shorter progression-free survival (10.23 vs 14.1 months) than carriers of G/G (n = 59) in both univariate (HR = 1.87; 95%CI 1.26-2.78; p = 0.00163) and multivariate (HR = 2.03; 95%CI 1.25-3.3; p = 0.004) analysis. No association were observed in the bevacizumab cohort of TRIBE and FIRE-3. Conclusions: Our study demonstrates for the first time that STING and IFNB1 polymorphisms could predict outcomes of Cetuximab-based treatment in mCRC patients; These finding may provide insight for the combination of STING agonist and anti-EGFR treatment in mCRC patients.

The role of PP2A variants to predict outcome in patients (pts) with metastatic colorectal cancer (mCRC): Data from FIRE-3 and TRIBE trials.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3581-3581
Author(s):  
Jingyuan Wang ◽  
Joshua Millstein ◽  
Fotios Loupakis ◽  
Sebastian Stintzing ◽  
Hiroyuki Arai ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Progression Free Survival ◽  
Snp Markers ◽  
Discovery Cohort ◽  
Increased Risk ◽  
Phosphatase 2A ◽  
Cell Signaling Networks ◽  
Risk Of Cancer ◽  
The Impact

3581 Background: Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase with functions that counter-balance kinase-mediated phosphorylation throughout cell signaling networks. PP2A was reported to upregulate the angiogenesis, while negatively regulate the pathways downstream of receptor tyrosine kinases at multiple nodes. Previous studies showed PP2A variants were associated with the increased risk of cancer. Therefore, we hypothesized that PP2A variants may predict first-line treatment outcome in mCRC pts treated with bevacizumab (bev)/cetuximab (cet)-based chemotherapy. Methods: Genomic DNA from blood samples of pts enrolled in two independent randomized trials, TRIBE (bev arm, n=215, as discovery cohort) and FIRE-3 (bev arm, n=107, as validation cohort; cet arm, n=129, as control cohort), was genotyped through the OncoArray, a customized array manufactured by Illumina including approximately 530K SNP markers. The impact on outcome of 17 selected SNPs in 3 main PP2A core subunits (PPP2CA, PPP2R1B, PPP2R1A), one phosphatase activator (PPP2R4) and 2 endogenous inhibitors (TIPRL, CIP2A) was analyzed. Results: In the discovery cohort, pts with PPP2R4 rs2541164 A/A (N=16) showed significantly shorter overall survival (15.3 vs 27.3 months) compared to carriers of any G allele (N=198) in both univariate (hazard ratio [HR]=1.8; 95% confidence interval [CI]: 1.1-3.1; p=0.02) and multivariate (HR=2.4; 95%CI: 1.4-4.4; p=0.006) analysis. These data were validated in the FIRE-3 bev cohort in both univariate (A/A vs. Any G: 17.3 vs 39.9 months, HR=2.8, 95%CI: 1.4-5.9, p=0.004) and multivariate (HR=4.3, 95%CI: 1.5-12.2, p=0.0095) analysis. Conversely, pts carrying CIP2A rs13069780 C/C (N=24) only showed significantly longer progression-free survival (17.7 vs 12.3 months) than carriers of any T allele (n=105) in the FIRE-3 cet cohort in both univariate (HR=0.6; 95%CI 0.4-0.99; p=0.04) and multivariate (HR=0.5; 95%CI 0.3-0.94; p=0.02) analysis, but no association were observed in the bev cohort of TRIBE and FIRE-3. Conclusions: Our study demonstrated for the first time that PPP2R4 polymorphisms could predict outcomes of bev-based treatment in mCRC patients; Meanwhile CIP2A polymorphism could predict outcomes of cet-based treatment in mCRC patients. These findings support a possible role of the PP2A variants in contributing to resistance to anti-VEGF/EGFR treatment.

scholarly journals Management of colorectal cancer in the era of COVID-19: Challenges and suggestions

2021 ◽  
Vol 104 (2) ◽  
pp. 003685042110106
Author(s):  
Walid Alam ◽  
Youssef Bouferraa ◽  
Yolla Haibe ◽  
Deborah Mukherji ◽  
Ali Shamseddine
Keyword(s):  
Colorectal Cancer ◽  
Treatment Protocols ◽  
Cancer Management ◽  
Increased Risk ◽  
Huge Impact ◽  
Treatment Plans ◽  
Virus Exposure ◽  
Risk Of Exposure ◽  
Colorectal Cancer Patients ◽  
The Impact

The Coronavirus (COVID-19) pandemic had a huge impact on all sectors around the world. In particular, the healthcare system has been subject to an enormous pressure that has surpassed its ability in many instances. Additionally, the pandemic has called for a review of our daily medical practices, including our approach to colorectal cancer management where treatment puts patients at high risk of virus exposure. Given their higher median age, patients are at an increased risk for severe symptoms and complications in cases of infection, especially in the setting of immunosuppression. Therefore, a review of the routine colorectal cancer practices is needed to minimize risk of exposure. Oncologists should weigh risk of exposure versus the patient’s oncologic benefits when approaching management. In addition, treatment protocols should be modified to minimize hospital visits and admissions while maintaining the same treatment efficacy. In this review, we will focus on challenges that colorectal cancer patients face during the pandemic, while highlighting the priority in each case. We will also discuss the evidence for potential modifications to existing treatment plans that could reduce infectious exposure without compromising care. Finally, we will discuss the impact of the socio-economic difficulties faced by Lebanese patients due to a poor economy toppled by an unexpected pandemic.

Lonsurf (trifluridine/tipiracil): Assessing the impact of dose related toxicities and progression free survival in (refractory) metastatic colorectal cancer

2021 ◽  
pp. 107815522110179
Author(s):  
Olivia R Court
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Dose Reduction ◽  
Progression Free Survival ◽  
Electronic Patient Records ◽  
Free Survival ◽  
Length Of Treatment ◽  
Common Grade ◽  
Grade 3 ◽  
The Impact

In the RECOURSE trial which lead to its accreditation, Lonsurf (trifluridine/tipiracil) was shown to extend progression free survival (PFS) by 1.8 months in metastatic colorectal cancer. This Trust audit aims to assess the average quantity of cycles of Lonsurf received by participants and the length of time it extends PFS. Similarly, to identify how many participants required a dose-reduction or experienced toxicities which necessitated supportive therapies. Quantitative data was collected retrospectively from all participants who had received ≥1 cycle of Lonsurf from The Clatterbridge Cancer Centre (CCC) from 2016 until June 2020. Participant electronic patient records were accessed to identify toxicity grading, length of treatment received, the date progression was identified, if dose reductions were applied and if supportive therapies were administered. Lonsurf extends PFS in patients with metastatic colorectal cancer at CCC by 3.0 months (95% CI: 2.73–3.27) and average treatment length was 2.4 months. However, 78 participants (41.5%) received a dose reduction due to toxicities. A total of 955 toxicities were recorded by participants; the most commonly reported toxicities irrespective of grade were fatigue (33.8%), diarrhoea (13.8%) and nausea (12.3%). The most common grade ≥3 toxicities were constipation and infection. The most frequently utilised supportive therapies were loperamide (49.6%) and domperidone (49.1%). Granulocyte colony stimulating factor (GCSF) was required by patients on 5 occasions (0.3%) in total. Lonsurf extends median PFS in patients with metastatic colorectal cancer by 3.0 months. The most common grade ≥3 toxicities which necessitated supportive therapies or a dose reduction were gastrointestinal and infection.

scholarly journals Treatment with Antiangiogenic Drugs in Multiple Lines in Patients with Metastatic Colorectal Cancer: Meta-Analysis of Randomized Trials

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
R.-D. Hofheinz ◽  
U. Ronellenfitsch ◽  
S. Kubicka ◽  
A. Falcone ◽  
I. Burkholder ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Optimal Sequence ◽  
Primary Endpoints ◽  
Disease Stabilization ◽  
Antiangiogenic Drugs ◽  
The Impact

Background. In metastatic colorectal cancer (mCRC), continuing antiangiogenic drugs beyond progression might provide clinical benefit. We synthesized the available evidence in a meta-analysis.Patients and Methods. We conducted a meta-analysis of studies investigating the use of antiangiogenic drugs beyond progression. Eligible studies were randomized phase II/III trials. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints were the impact of continuing antiangiogenic drugs (i) in subgroups, (ii) in different types of compounds targeting the VEGF-axis (monoclonal antibodies versus tyrosine kinase inhibitors), and (iii) on remission rates and prevention of progression.Results. Eight studies (3,668 patients) were included. Continuing antiangiogenic treatment beyond progression significantly improved PFS (HR 0.64; 95%-CI, 0.55–0.75) and OS (HR 0.83; 95%-CI, 0.76–0.89). PFS was significantly improved in all subgroups with comparable HR. OS was improved in all subgroups stratified by age, gender, and ECOG status. The rate of patients achieving at least stable disease was improved with an OR of 2.25 (95%-CI, 1.41–3.58).Conclusions. This analysis shows a significant PFS and OS benefit as well as a benefit regarding disease stabilization when using antiangiogenic drugs beyond progression in mCRC. Future studies should focus on the optimal sequence of administering antiangiogenic drugs.

scholarly journals Prenatal hyperandrogenism induces alterations that affect liver lipid metabolism

2016 ◽  
Vol 230 (1) ◽  
pp. 67-79 ◽  
Author(s):  
Giselle Adriana Abruzzese ◽  
Maria Florencia Heber ◽  
Silvana Rocio Ferreira ◽  
Leandro Martin Velez ◽  
Roxana Reynoso ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Lipid Metabolism ◽  
Glucose Tolerance ◽  
Fatty Liver ◽  
Lipid Content ◽  
Liver Lipid ◽  
Acid Oxidation ◽  
Liver Lipid Content ◽  
Increased Risk ◽  
Liver Lipid Metabolism

Prenatal hyperandrogenism is hypothesized as one of the main factors contributing to the development of polycystic ovary syndrome (PCOS). PCOS patients have high risk of developing fatty liver and steatosis. This study aimed to evaluate the role of prenatal hyperandrogenism in liver lipid metabolism and fatty liver development. Pregnant rats were hyperandrogenized with testosterone. At pubertal age, the prenatally hyperandrogenized (PH) female offspring displayed both ovulatory (PHov) and anovulatory (PHanov) phenotypes that mimic human PCOS features. We evaluated hepatic transferases, liver lipid content, the balance between lipogenesis and fatty acid oxidation pathway, oxidant/antioxidant balance and proinflammatory status. We also evaluated the general metabolic status through growth rate curve, basal glucose and insulin levels, glucose tolerance test, HOMA-IR index and serum lipid profile. Although neither PH group showed signs of liver lipid content, the lipogenesis and fatty oxidation pathways were altered. The PH groups also showed impaired oxidant/antioxidant balance, a decrease in the proinflammatory pathway (measured by prostaglandin E2 and cyclooxygenase-2 levels), decreased glucose tolerance, imbalance of circulating lipids and increased risk of metabolic syndrome. We conclude that prenatal hyperandrogenism generates both PHov and PHanov phenotypes with signs of liver alterations, imbalance in lipid metabolism and increased risk of developing metabolic syndrome. The anovulatory phenotype showed more alterations in liver lipogenesis and a more impaired balance of insulin and glucose metabolism, being more susceptible to the development of steatosis.

KRASandBRAFMutations in Advanced Colorectal Cancer Are Associated With Poor Prognosis but Do Not Preclude Benefit From Oxaliplatin or Irinotecan: Results From the MRC FOCUS Trial

2009 ◽  
Vol 27 (35) ◽  
pp. 5931-5937 ◽  
Author(s):  
Susan D. Richman ◽  
Matthew T. Seymour ◽  
Philip Chambers ◽  
Faye Elliott ◽  
Catherine L. Daly ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Braf Mutation ◽  
Poor Prognosis ◽  
Advanced Colorectal Cancer ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Poor Prognostic Factor ◽  
Minimal Impact ◽  
The Impact

PurposeActivating mutation of the KRAS oncogene is an established predictive biomarker for resistance to anti–epidermal growth factor receptor (anti-EGFR) therapies in advanced colorectal cancer (aCRC). We wanted to determine whether KRAS and/or BRAF mutation is also a predictive biomarker for other aCRC therapies.Patients and MethodsThe Medical Research Council Fluorouracil, Oxaliplatin and Irinotecan: Use and Sequencing (MRC FOCUS) trial compared treatment sequences including first-line fluorouracil (FU), FU/irinotecan or FU/oxaliplatin in aCRC. Tumor blocks were obtained from 711 consenting patients. DNA was extracted and KRAS codons 12, 13, and 61 and BRAF codon 600 were assessed by pyrosequencing. Mutation (mut) status was assessed first as a prognostic factor and then as a predictive biomarker for the benefit of adding irinotecan or oxaliplatin to FU. The association of BRAF-mut with loss of MLH1 was assessed by immunohistochemistry.ResultsThree hundred eight (43.3%) of 711 patients had KRAS-mut and 56 (7.9%) of 711 had BRAF-mut. Mutation of KRAS, BRAF, or both was present in 360 (50.6%) of 711 patients. Mutation in either KRAS or BRAF was a poor prognostic factor for overall survival (OS; hazard ratio [HR], 1.40; 95% CI, 1.20 to 1.65; P < .0001) but had minimal impact on progression-free survival (PFS; HR, 1.16; 95% CI, 1.00 to 1.36; P = .05). Mutation status did not affect the impact of irinotecan or oxaliplatin on PFS or OS. BRAF-mut was weakly associated with loss of MLH1 staining (P = .012).ConclusionKRAS/BRAF mutation is associated with poor prognosis but is not a predictive biomarker for irinotecan or oxaliplatin. There is no evidence that patients with KRAS/BRAF mutated tumors are less likely to benefit from these standard chemotherapy agents.

scholarly journals Genetic Variants in Lipid Metabolism Pathways Interact with Diet to Influence Blood Lipid Concentrations in Adults with Overweight and Obesity

2020 ◽  
Vol 13 (6) ◽  
pp. 155-163
Author(s):  
Bridget A. Hannon ◽  
Caitlyn G. Edwards ◽  
Sharon V. Thompson ◽  
Sarah K. Burke ◽  
Nicholas A. Burd ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Dietary Intake ◽  
Dietary Fat ◽  
Genetic Variants ◽  
Blood Lipid ◽  
Overweight And Obesity ◽  
Cardiometabolic Health ◽  
Fat Intake ◽  
Dietary Fat Intake ◽  
Increased Risk

<b><i>Introduction:</i></b> The effect of various types of dietary fat on cardiometabolic health continues to be debated, due in part to the high heterogeneity of results following clinical trials investigating the effects of saturated (SFA) and unsaturated fat intake. This variability may be due to genetic differences. Individuals with obesity are at an increased risk for adverse cardiometabolic health and dyslipidemia, and often present with the combined phenotype of elevated triglyceride (TG) and decreased high-density lipoprotein (HDL) cholesterol concentrations. Studying genetic variants relevant to lipid and lipoprotein metabolism can elucidate the mechanisms by which diet might interact with genotype to influence these phenotypes. The objective of this study was to determine relationships of genetic variation, dietary fat intake, and blood lipid concentrations in adults with overweight and obesity. <b><i>Methods:</i></b> Genomic DNA, blood lipid concentrations (HDL and TG), and 7-day diet records were obtained from 101 adults (25–45 years of age) with overweight or obesity. Resting energy expenditure (REE) was measured using indirect calorimetry and used to determine implausible intakes using a modified Goldberg method (kilocalories/REE). Genetic variants included 23 single-nucleotide polymorphisms (SNPs) from 15 genes in lipid metabolism pathways. Variants were analyzed with dietary fat intake (total fat, SFA, monounsaturated fat [MUFA], and polyunsaturated fat [PUFA]) via regression analyses. All models were adjusted for age, sex, ancestry, visceral adipose tissue mass, and total kilocalorie intake. The Bonferroni correction was applied for multiple comparisons. <b><i>Results:</i></b> Two interactions were detected for TG concentrations. Five gene-diet interactions were associated with HDL concentrations. There was a significant interaction detected between the rs5882 variant of cholesterol-esterase transfer protein (<i>CETP</i>) and MUFA intake to associate with TG concentrations (interaction <i>p</i> = 0.004, <i>R</i><sup>2</sup> = 0.306). Among carriers of the <i>CETP-</i>rs5882 major allele (G), TG concentrations were significantly lower in individuals consuming more than the median MUFA intake (31 g/day) than in those with an intake below the median. Total dietary fat intake interacted with the rs13702 polymorphism of lipoprotein lipase (<i>LPL</i>) to associate with HDL concentrations (interaction <i>p</i> = 0.041, <i>R</i><sup>2</sup> = 0.419), by which individuals with the risk allele (G) had significantly higher HDL concentrations when consuming a higher-fat diet (&#x3e;92 g/day) than those with a lower-fat diet (56 ± 3 vs. 46 ± 2 mg/dL, <i>p</i> = 0.033). <b><i>Conclusions:</i></b> Interactions between dietary intake and genes in lipid metabolism pathways were found to be associated with blood lipid concentrations in adults with overweight and obesity. Fatty acid intake may not modulate blood lipid concentrations uniformly across all individuals. Additional research is needed to determine the biological causes of individual variability in response to dietary intake. Understanding the influence of nutrigenetic interactions on dyslipidemia can aid in the development and implementation of personalized dietary strategies to improve health.

scholarly journals Renin–angiotensin system blocker use and the risk of acute kidney injury after colorectal cancer surgery: a population-based cohort study

BMJ Open ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. e032964
Author(s):  
Charlotte Slagelse ◽  
H Gammelager ◽  
Lene Hjerrild Iversen ◽  
Kathleen D Liu ◽  
Henrik T Toft Sørensen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Acute Kidney Injury ◽  
Cohort Study ◽  
Angiotensin Receptor Blockers ◽  
Kidney Injury ◽  
Population Based ◽  
Adjusted Risk ◽  
Increased Risk ◽  
The Impact ◽  
Postoperative Aki

ObjectivesIt is unknown whether preoperative use of ACE inhibitors (ACE-I) or angiotensin receptor blockers (ARBs) affects the risk of acute kidney injury (AKI) after colorectal cancer (CRC) surgery. We assessed the impact of preoperative ACE-I/ARB use on risk of AKI after CRC surgery.DesignObservational cohort study. Patients were divided into three exposure groups—current, former and non-users—through reimbursed prescriptions within 365 days before the surgery. AKI within 7 days after surgery was defined according to the current Kidney Disease Improving Global Outcome consensus criteria.SettingPopulation-based Danish medical databases.ParticipantsA total of 9932 patients undergoing incident CRC surgery during 2005–2014 in northern Denmark were included through the Danish Colorectal Cancer Group Database.Outcome measureWe computed cumulative incidence proportions (risk) of AKI with 95% CIs for current, former and non-users of ACE-I/ARB, including death as a competing risk. We compared current and former users with non-users by computing adjusted risk ratios (aRRs) using log-binomial regression adjusted for demographics, comorbidities and CRC-related characteristics. We stratified the analyses of ACE-I/ARB users to address any difference in impact within relevant subgroups.ResultsTwenty-one per cent were ACE-I/ARB current users, 6.4% former users and 72.3% non-users. The 7-day postoperative AKI risk for current, former and non-users was 26.4% (95% CI 24.6% to 28.3%), 25.2% (21.9% to 28.6%) and 17.8% (17.0% to 18.7%), respectively. The aRRs of AKI were 1.20 (1.09 to 1.32) and 1.16 (1.01 to 1.34) for current and former users, compared with non-users. The relative risk of AKI in current compared with non-users was consistent in all subgroups, except for higher aRR in patients with a history of hypertension.ConclusionsBeing a current or former user of ACE-I/ARBs is associated with an increased risk of postoperative AKI compared with non-users. Although it may not be a drug effect, users of ACE-I/ARBs should be considered a risk group for postoperative AKI.

scholarly journals Coadjuvant Anti-VEGF A Therapy Improves Survival in Patients with Colorectal Cancer with Liver Metastasis: A Systematic Review

2020 ◽  
Vol 2 (2) ◽  
pp. 71-85
Author(s):  
Isabel Novo ◽  
Bárbara Campos ◽  
Filipa Pinto-Ribeiro ◽  
Sandra F. Martins
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Liver Metastasis ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Vascular Endothelial ◽  
Inclusion Criteria ◽  
Effective Treatment Modality ◽  
Endothelial Growth Factor ◽  
The Impact

Background: the presence of liver metastasis in colorectal cancer (CRC) remains one of the most significant prognostic factors. Objective: systematically review the results of studies evaluating the benefit of adding bevacizumab to a normal chemotherapy regime in the survival of patients with colorectal-cancer liver metastasis (CRLM). Search methods: Pubmed and Google Scholar databases were searched for eligible articles (from inception up to the 2 April 2019). Inclusion criteria: studies including patients with CRLM receiving anti-vascular endothelial growth factor (VEGF; bevacizumab) as treatment, overall survival as an outcome; regarding language restrictions, only articles in English were accepted. Main results: Eleven studies met the inclusion criteria. In 73% of these cases, chemotherapy with bevacizumab was an effective treatment modality for treating CRLM, and its administration significantly extended both overall survival (OS) and/or progression-free survival (PFS). Nevertheless, three articles showed no influence on survival rates of bevacizumab-associated chemotherapy. Author conclusions: It is necessary to standardize methodologies that aim to evaluate the impact of bevacizumab administration on the survival of patients with CRLM. Furthermore, follow-up time and the cause of a patient’s death should be recorded, specified, and cleared in order to better calculate the survival rate and provide a comparison between the produced literature.

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