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Metabolic phenotypes and risk of colorectal cancer: a systematic review and meta-analysis of cohort studies.
Goodarzi, G, Mozaffari, H, Raeisi, T, Mehravar, F, Razi, B, Ghazi, ML, Garousi, N, Alizadeh, S, Janmohammadi, P
BMC cancer. 2022;(1):89
Abstract
BACKGROUND The association of obesity with colorectal cancer (CRC) may vary depending on metabolic status. OBJECTIVE This meta-analysis aimed to investigate the combined impacts of obesity and metabolic status on CRC risk. METHODS The Scopus, PubMed, and web of sciences databases were systematically searched up to Jun 2021 to find all eligible publications examining CRC risk in individuals with metabolically unhealthy normal-weight (MUHNW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUHO) phenotypes. RESULTS A total of 7 cohort studies with a total of 759,066 participants were included in this meta-analysis. Compared with healthy normal-weight people, MUHNW, MHO, and MUHO individuals indicated an increased risk for CRC with a pooled odds ratio of 1.19 (95% CI = 1.09-1.31) in MUHNW, 1.14 (95% CI = 1.06-1.22) in MHO, and 1.24 (95% CI = 1.19-1.29) in MUHO subjects. When analyses were stratified based on gender, associations remained significant for males. However, the elevated risk of CRC associated with MHO and MUHO was not significant in female participants. CONCLUSIONS The individuals with metabolic abnormality, although at a normal weight, have an increased risk for CRC. Moreover, obesity is associated with CRC irrespective of metabolic status.
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Nitrate-nitrite exposure through drinking water and diet and risk of colorectal cancer: A systematic review and meta-analysis of observational studies.
Hosseini, F, Majdi, M, Naghshi, S, Sheikhhossein, F, Djafarian, K, Shab-Bidar, S
Clinical nutrition (Edinburgh, Scotland). 2021;(5):3073-3081
Abstract
BACKGROUND Considerable controversy exists regarding the association between nitrate intake and risk of colorectal cancer. Therefore, we performed a dose-response meta-analysis of observational studies. METHODS We identified relevant studies by searching PubMed, Scopus and ISI Web of Knowledge until April 2020 and references of retrieved relevant articles. The random-effects model was used to calculate pooled effect size (ESs) and 95% confidence intervals (CIs). RESULTS Fifteen prospective cohort and case-control papers were included in this systematic review and meta-analysis. In total, 2,573,524 participants with an age range between 20 and 85 years were included. The total number of colorectal cancer cases was 38,848. Intake of nitrate from diet was associated with a risk of colorectal cancer (Pooled HR: 1.13; 95% CI: 1.04-1.23, I2 = 38%; P = 0.08). Nitrite in diet was not significantly associated with risk of colorectal cancer (pooled HR: 1.07; 95% CI: 0.95-1.21, I2 = 61.6%; P = 0.005). Nitrate in water did not show an association with risk of colorectal cancer (pooled HR: 1.04; 95% CI: 0.92-1.19, I2 = 64.7%; P = 0.002). Non-linear dose-response analysis revealed no significant association of dietary nitrite and also nitrate of drinking water with risk of colorectal cancer. However, dietary nitrate was marginally associated with a greater risk of colorectal cancer. Linear dose-response analysis of nitrate from diet was not associated with colorectal cancer risk by an additional 50 mg per day. Such a non-significant association was also seen for colorectal cancer risk by an additional 1 mg per day and 1 mg/l from dietary nitrite and water nitrate respectively. CONCLUSIONS Dietary nitrate was related to a higher risk of colorectal cancer risk. However, intake of nitrite from diet and nitrate from the drinking water was not associated with colorectal cancer risk.
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A Meta-Analysis of Obesity and Risk of Colorectal Cancer in Patients with Lynch Syndrome: The Impact of Sex and Genetics.
Lazzeroni, M, Bellerba, F, Calvello, M, Macrae, F, Win, AK, Jenkins, M, Serrano, D, Marabelli, M, Cagnacci, S, Tolva, G, et al
Nutrients. 2021;(5)
Abstract
There appears to be a sex-specific association between obesity and colorectal neoplasia in patients with Lynch Syndrome (LS). We meta-analyzed studies reporting on obesity and colorectal cancer (CRC) risk in LS patients to test whether obese subjects were at increased risk of cancer compared to those of normal weight. We explored also a possible sex-specific relationship between adiposity and CRC risk among patients with LS. The summary relative risk (SRR) and 95% confidence intervals (CI) were calculated through random effect models. We investigated the causes of between-study heterogeneity and assessed the presence of publication bias. We were able to retrieve suitable data from four independent studies. We found a twofold risk of CRC in obese men compared to nonobese men (SRR = 2.09; 95%CI: 1.23-3.55, I2 = 33%), and no indication of publication bias (p = 0.13). No significantly increased risk due to obesity was found for women. A 49% increased CRC risk for obesity was found for subjects with an MLH1 mutation (SRR = 1.49; 95%CI: 1.11-1.99, I2 = 0%). These results confirm the different effects of sex on obesity and CRC risk and also support the public measures to reduce overweight in people with LS, particularly for men.
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Are the FTO Gene Polymorphisms Associated with Colorectal Cancer? A Meta-analysis.
Gholamalizadeh, M, Tabrizi, R, Bourbour, F, Rezaei, S, Pourtaheri, A, Badeli, M, Jarrahi, SAM, Akbari, ME, Kalantari, N, Doaei, S
Journal of gastrointestinal cancer. 2021;(3):846-853
Abstract
BACKGROUND Colorectal cancer (CRC) is reported to be associated with some gene polymorphisms. However, the effect of the fat mass and obesity associated (FTO) gene on colorectal cancer is not yet clear. This meta-analysis aimed to investigate the association of the FTO gene polymorphism and colorectal cancer. METHODS PubMed, Web of science, Scopus, and Embase were explored to identify the studies investigating the relationship between rs9939609 and rs17817449 polymorphisms of FTO gene and colorectal cancer, and the published papers from 2000 to 2019 were collected. This meta-analysis was conducted by using a random-effects model for the best estimation of the desired outcomes. RESULTS In this study, 1528 studies were initially included and five eligible case-control studies including 13,460 cases and 22,578 controls were eligible for further analyses. No significant association was found between risk allele of FTO rs9939609 (OR = 0.98, 0.87-1.1) and rs17817449 (OR = 0.9, 0.79-1.03) polymorphisms and colorectal cancer risk. The subgroup analyses considering the source of the control group and race found no significant association between FTO polymorphisms and the risk of colon cancer. CONCLUSIONS This study indicated that rs9939609 and rs17817449 FTO gene polymorphisms are not associated with colorectal cancer risk. Individual studies involving different FTO polymorphisms are needed to further evaluation of the associations between the FTO gene and colon cancer.
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The efficacy and safety of bevacizumab combined with FOLFOX regimen in the treatment of advanced colorectal cancer: A systematic review and meta-analysis.
Zhang, H, You, J, Liu, W, Chen, D, Zhang, S, Wang, X
Medicine. 2021;(30):e26714
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Abstract
BACKGROUND It is necessary to systematically evaluate the clinical efficacy and safety of bevacizumab (BEV) combined with 5-fluorouracil + leucovorin + oxaliplatin (FOLFOX) regimen in the treatment of advanced colorectal cancer. METHODS We searched the PubMed et al databases for randomized controlled trials (RCTs) on the BEV combined with the FOLFOX regimen in the treatment of advanced colorectal cancer up to January 20, 2021. The Cochrane Collaborations' risk of bias tool was used for the quality assessment of included RCTs. Revman5.3 software was used for meta-analysis. RESULTS Eleven RCTs with a total of 3178 patients with advanced colorectal cancer were included, meta-analysis results showed that the objective response rate (odds ratio [OR] = 3.15, 95% confidence intervals [CI]: 2.25-4.40, P < .001) and cancer control rate (OR = 2.73, 95% CI: 1.91-3.90, P < .001) of BEV + FOLFOX were higher than that of FOLFOX group. And the incidence of gastrointestinal adverse reactions (OR = 1.29, 95% CI: 1.07-1.55, P = .008) in the BEV + FOLFOX group was higher than that of the FOLFOX group, there were no significant differences in the incidence of leukopenia (OR = 1.04, 95% CI: 0.72-1.50, P = .83), hypertension (OR = 3.92, 95% CI: 0.81-18.88, P = .09) and neurotoxicity (OR = 1.00, 95% CI: 0.8-1.27, P = .98) between the 2 groups. CONCLUSION BEV combined with the FOLFOX regimen is more effective than the FOLFOX regimen alone in the treatment of advanced colorectal cancer, but it may also increase the risk of gastrointestinal adverse reactions.
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Non-steroidal anti-inflammatory agents and anastomotic leak rates across colorectal cancer operations and anastomotic sites: A systematic review and meta-analysis of anastomosis specific leak rate and confounding factors.
Kastora, SL, Osborne, LL, Jardine, R, Kounidas, G, Carter, B, Myint, PK
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2021;(11):2841-2848
Abstract
BACKGROUND Surgical intervention presents a fundamental therapeutic choice in the management of colorectal malignancies. Complications, the most serious one being anastomotic leak (AL), still have detrimental effects upon patients' morbidity and mortality. We aimed to assess whether NSAIDs, and their sub-categories, increase AL in colonic anastomoses and to identify whether this affects specific anastomotic sites. MATERIALS AND METHODS A systematic search of MEDLINE, Cochrane Library, ClinicalTrials.gov, Web of Science, Science Direct, Google Scholar was conducted between January 1, 1999 till the October 30, 2020. Cohort studies and randomized control trials examining AL events in NSAID-exposed, colorectal cancer patients were included. NSAIDs were grouped according to the 2019 NICE guidelines in non-specific (NS-NSAIDs) and specific COX-2 inhibitors. The primary outcome was AL events in NSAID-exposed patients undergoing operations with either ileocolic, colocolic or colorectal anastomoses. Secondary outcomes included NSAID category-specific AL events and demographic confounding factors increasing AL risk in this patient population. RESULTS Fifteen studies involving 25,395 patients were included in the systematic review and meta-analysis. Of all anastomoses, colocolic anastomoses were found to be statistically more prone to AL events in the NS-NSAID-exposed population [OR 3.24 (95% CI 0.98-10.72), p = 0.054]. Male gender was an independent confounder increasing AL rate regardless of NSAID exposure. CONCLUSION The association between NSAID exposure and AL in oncology patients remains undetermined. Whilst in present work, colocolic anastomoses appear to be more sensitive to AL events, the observed association may be anastomotic site and NSAID-category dependent.
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Effectiveness of diet and physical activity interventions amongst adults attending colorectal and breast cancer screening: a systematic review and meta-analysis.
Orange, ST, Hicks, KM, Saxton, JM
Cancer causes & control : CCC. 2021;(1):13-26
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PURPOSE To estimate the effectiveness of tailored physical activity and dietary interventions amongst adults attending colorectal and breast cancer screening. METHODS Five literature databases were systematically searched to identify randomised controlled trials (RCTs) of tailored physical activity and/or dietary interventions with follow-up support initiated through colorectal and breast cancer screening programmes. Outcomes included markers of body fatness, physical activity, and dietary intake. Mean differences (MDs) or standardised mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using random effects models. RESULTS Five RCTs met the inclusion criteria encompassing a total of 722 participants. Diet and physical activity interventions led to statistically significant reductions in body mass (MD - 1.6 kg, 95% CI - 2.7 to - 0.39 kg; I2 = 81%; low quality evidence), body mass index (MD - 0.78 kg/m2, 95% CI - 1.1 to - 0.50 kg/m2; I2 = 21%; moderate quality evidence), and waist circumference (MD - 2.9 cm, 95% CI - 3.8 to - 1.91; I2 = 0%; moderate quality evidence), accompanied by an increase in physical activity (SMD 0.31, 95% CI 0.13 to 0.50; I2 = 0%; low quality evidence) and fruit and vegetable intake (SMD 0.33, 95% CI 0.01 to 0.64; I2 = 51%; low quality evidence). CONCLUSION There is low quality evidence that lifestyle interventions involving follow-up support lead to modest weight loss and increased physical activity and fruit and vegetable intake. Due to the modest intervention effects, low quality of evidence and small number of studies, further rigorously designed RCTs with long-term follow-up of modifiable risk factors and embedded cost-benefit analyses are warranted (PROSPERO ref: CRD42020179960).
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Mobile health technologies supporting colonoscopy preparation: A systematic review and meta-analysis of randomized controlled trials.
El Bizri, M, El Sheikh, M, Lee, GE, Sewitch, MJ
PloS one. 2021;(3):e0248679
Abstract
BACKGROUND Mobile health (mHealth) technologies are innovative solutions for delivering instructions to patients preparing for colonoscopy. OBJECTIVE To systematically review the literature evaluating the effectiveness of mHealth technologies supporting colonoscopy preparation on patient and clinical outcomes. METHODS MEDLINE, EMBASE, CINAHL and CENTRAL were searched for randomized controlled trials (RCTs) that evaluated the effectiveness of mHealth technologies for colonoscopy preparation on patient and clinical outcomes. Two reviewers independently assessed study eligibility, extracted data, and appraised methodological quality using the Cochrane Risk-of-Bias tool. Data were pooled using random effects models and when heterogeneity, assessed using I2, was statistically significant, a qualitative synthesis of the data was performed. Publication bias was assessed using a funnel plot. RESULTS Ten RCTs (3,383 participants) met inclusion criteria. MHealth interventions included smartphone apps, SMS text messages, videos, camera apps, and a social media app. Outcomes were bowel cleanliness quality, user satisfaction, colonoscopy quality indicators (cecal intubation time, withdrawal time, adenoma detection rate), adherence to diet, and cancellation/no-show rates. MHealth interventions were associated with better bowel cleanliness scores on the Boston Bowel Preparation Scale [standardized mean difference (SMD) 0.57, 95%CI 0.37-0.77, I2 = 60%, p = 0.08] and the Ottawa Bowel Preparation Scale [SMD -0.39, 95%CI -0.59-0.19, I2 = 45%, p = 0.16], but they were not associated with rates of willingness to repeat the colonoscopy using the same regimen [odds ratio (OR) 1.88, 95%CI 0.85-4.15, I2 = 48%, p = 0.12] or cancellations/no-shows [OR 0.96, 95%CI 0.68-1.35, I2 = 0%]. Most studies showed that adequate bowel preparation, user satisfaction and adherence to diet were better in the intervention groups compared to the control groups, while inconsistent findings were observed for the colonoscopy quality indicators. All trials were at high risk of bias for lack of participant blinding. Visual inspection of a funnel plot revealed publication bias. CONCLUSIONS MHealth technologies show promise as a way to improve bowel cleanliness, but trials to date were of low methodological quality. High-quality research is required to understand the effectiveness of mHealth technologies on colonoscopy outcomes.
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Efficacy and safety of high-dose vs low-dose leucovorin in patients with colorectal cancer: systematic review and meta-analysis.
Hsu, CY, Chen, CY, Lin, YM, Tam, KW
Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland. 2020;(1):6-17
Abstract
AIM: The clinical benefits of a combination of leucovorin and fluorouracil have been established in the treatment of colorectal cancer. Due to a leucovorin shortage in 2008, many institutions revised their protocols to reduce the dose of leucovorin. After the shortage was resolved, some hospitals still maintained their modified protocols. Thus, we conducted a systematic review to evaluate the efficacy and safety of low- vs high-dose leucovorin in the treatment of colorectal cancer. METHOD The PubMed, Embase and Cochrane databases were searched for studies published before May 2019. The meta-analysis was performed to estimate the pooled effect sizes by using a random effect model. The primary outcomes were median survival time and tumour response rate. Secondary outcomes were haematological and nonhaematological toxicities. RESULTS Eight randomized controlled trials and four retrospective studies were reviewed. The pooled median survival time was similar between the two dose levels (standard mean difference -0.06, 95% CI -0.19 to 0.08). The pooled tumour response rate was comparatively higher in the high-dose leucovorin regimen (OR 0.81; 95% CI 0.55-1.18). No statistically significant difference was found between the haematological and nonhaematological toxicities of the two groups. However, there were fewer diarrhoea events in the low-dose leucovorin regimen. CONCLUSION Low-dose leucovorin regimens seemed feasible approaches for colorectal cancer treatment when the shortage happened, because both regimens manifested comparable outcomes in survival time and tumour response rate.
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Risk factors for postoperative delirium after colorectal surgery: a systematic review and meta-analysis.
Lee, SH, Lim, SW
International journal of colorectal disease. 2020;(3):433-444
Abstract
PURPOSE Postoperative delirium is common after any type of surgery and can lead to serious outcomes; thus, its prevention is important. Early assessment can help identify patients at higher risk of postoperative delirium. However, the risk factors for postoperative delirium in patients who underwent colorectal surgery are unclear. This meta-analysis aimed to identify the risk factors for postoperative delirium after colorectal cancer surgery. METHODS We selected all articles related to postoperative delirium after colorectal surgery published up to March 2019. Studies using any method for diagnosing delirium were eligible. Ovid-Embase, Ovid-Medline, and the Cochrane library were searched. Two reviewers independently conducted quality assessment and data collection. The risk factors identified in the studies were recorded, and a meta-analysis was conducted. RESULTS Of the 1216 studies initially screened, 1197 were reviewed by two independent reviewers. Finally, 14 articles were identified to be relevant for this review. In total, 11 of the 14 studies reported the risk factors for postoperative delirium. The incidence of postoperative delirium ranged from 8% to 54%. A total of 19 risk factors were identified, and we classified them into two categories as patient-related and treatment-related risk factors. CONCLUSION Postoperative delirium is highly common in those undergoing colorectal surgery including cancer, with advanced old age, history of preoperative delirium and preoperative serum albumin level which are risk factors for POD. Larger multi-institutional randomized studies to address this issue are warranted in the future.