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Relation between preoperative aerobic fitness estimated by steep ramp test performance and postoperative morbidity in colorectal cancer surgery: prospective observational study.
Cuijpers, ACM, Heldens, AFJM, Bours, MJL, van Meeteren, NLU, Stassen, LPS, Lubbers, T, Bongers, BC
The British journal of surgery. 2022;(2):155-159
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Abstract
Steep ramp test (SRT) performance provides an estimation of preoperative aerobic fitness that is associated with postoperative outcomes. Patients with a better SRT-estimated aerobic fitness are less likely to develop postoperative complications and more likely to experience a shorter time to recovery. The SRT might be a useful and clinically accessible tool in preoperative risk assessment to identify patients at risk of postoperative morbidity and who might benefit from preoperative exercise interventions.
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Technical efficiency evaluation of colorectal cancer care for older patients in Dutch hospitals.
Heil, TC, Melis, RJF, Maas, HAAM, van Munster, BC, Olde Rikkert, MGM, de Wilt, JHW, Adang, EMM, ,
PloS one. 2021;(12):e0260870
Abstract
BACKGROUND Preoperative colorectal cancer care pathways for older patients show considerable practice variation between Dutch hospitals due to differences in interpretation and implementation of guideline-based recommendations. This study aims to report this practice variation in preoperative care between Dutch hospitals in terms of technical efficiency and identifying associated factors. METHODS Data on preoperative involvement of geriatricians, physical therapists and dieticians and the clinicians' judgement on prehabilitation implementation were collected using quality indicators and questionnaires among colorectal cancer surgeons and specialized nurses. These data were combined with registry-based data on postoperative outcomes obtained from the Dutch Surgical Colorectal Audit for patients aged ≥75 years. A two-stage data envelopment analysis (DEA) approach was used to calculate bias-corrected DEA technical efficiency scores, reflecting the extent to which a hospital invests in multidisciplinary preoperative care (input) in relation to postoperative outcomes (output). In the second stage, hospital care characteristics were used in a bootstrap truncated regression to explain variations in measured efficiency scores. RESULTS Data of 25 Dutch hospitals were analyzed. There was relevant practice variation in bias-corrected technical efficiency scores (ranging from 0.416 to 0.968) regarding preoperative colorectal cancer surgery. The average efficiency score of hospitals was significantly different from the efficient frontier (p = <0.001). After case-mix correction, higher technical efficiency was associated with larger practice size (p = <0.001), surgery performed in a general hospital versus a university hospital (p = <0.001) and implementation of prehabilitation (p = <0.001). CONCLUSION This study showed considerable variation in technical efficiency of preoperative colorectal cancer care for older patients as provided by Dutch hospitals. In addition to higher technical efficiency in high-volume hospitals and general hospitals, offering a care pathway that includes prehabilitation was positively related to technical efficiency of hospitals offering colorectal cancer care.
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Association between lifestyle and site-specific advanced colorectal lesions in screening with faecal immunochemical test and sigmoidoscopy.
Knudsen, MD, Botteri, E, Holme, Ø, Hjartåker, A, Song, M, Thiis-Evensen, E, Norvard, ER, Schult, AL, Randel, KR, Hoff, G, et al
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2021;(3):353-359
Abstract
BACKGROUND Lifestyle factors may help to identify individuals at high-risk for colorectal cancer (CRC). AIMS To examine the association between lifestyle, referral for follow-up colonoscopy and proximal neoplasia detection in CRC screening. METHODS In this observational study, 14,832 individuals aged 50-74 years were invited to faecal immunochemical test (FIT) or sigmoidoscopy screening. Advanced lesions (AL), including advanced adenomas, advanced serrated lesions and CRC were divided according to location: distal-only, or proximal with or without distal AL. We collected information on smoking habit, body mass index and alcohol intake through a questionnaire. RESULTS Out of 3,318 FIT and 2,988 sigmoidoscopy participants, 516 (16%) and 338 (11%), respectively, were referred for follow-up colonoscopy after a positive screening test. Two-hundred-and-fifty-six (4%) had distal-only and 119 (2%) proximal AL. In FIT participants, obesity and high alcohol intake were associated with proximal AL; odds ratio (95% confidence interval) 2.68 (1.36-5.26) and 2.16 (1.08-4.30), respectively. In sigmoidoscopy participants, current smoking was associated with proximal AL; 4.58 (2.24-9.38), and current smoking and obesity were associated with referral for colonoscopy; 2.80 (2.02-3.89) and 1.42 (1.01-2.00), respectively. CONCLUSION Current smoking, obesity and high alcohol intake were associated with screen-detected proximal colorectal AL. Current smoking and obesity were associated with referral for follow-up colonoscopy in sigmoidoscopy screening.
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Prospective multicentre study of a new bowel obstruction treatment in colorectal surgery: Reduced morbidity and mortality.
Fahim, M, Dijksman, LM, Derksen, WJM, Bloemen, JG, Biesma, DH, Smits, AB
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2021;(9):2414-2420
Abstract
INTRODUCTION Bowel obstruction patients are at increased risk of emergency surgery and have poor nutritional and physical conditions. These patients could benefit from prehabilitation and prevention of emergency surgery. This study assessed the effect of a multimodal obstruction treatment for bowel obstruction patients in colorectal surgery on the risk of emergency surgery and postoperative morbidity and mortality. MATERIALS AND METHODS This multicenter observational cohort study included all consecutive bowel obstruction patients who received obstruction treatment (obstruction protocol) in the period 2019-2020 in two Dutch hospitals. Benign and malignant causes of bowel obstruction were included. Treatment consisted of 1. dietary adjustments, 2. postponing surgery for three weeks, 3. laxatives, and 4. prehabilitation. We compared emergency surgery and postoperative morbidity and mortality rates to known rates from the literature. RESULTS Eighty-nine patients were included: obstruction treatment was successful in 77 patients (87%) who underwent elective surgery and unsuccessful in 12 patients (13%) who underwent emergency surgery. Sixty-six (74%) had colorectal cancer, and 22 (25%) had benign disease. Thirty-day mortality of 0% in our study was significantly lower than the national average of 4% in colorectal cancer patients in the Netherlands (p = 0.049). Anastomotic leakage rate was 3%, severe complications (Clavien-Dindo ≥ III) 8%, and bowel perforation 0%. These rates did not differ significantly from rates reported in literature. CONCLUSION The obstruction treatment prevented emergency surgery in most patients with bowel obstruction and reduced postoperative morbidity and mortality. The obstruction treatment seems to be a safe and efficient alternative to emergency surgery.
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The association between the adapted dietary inflammatory index and colorectal cancer recurrence and all-cause mortality.
Wesselink, E, Staritsky, LE, van Zutphen, M, Geijsen, AJMR, Kok, DE, Kruyt, F, Veenstra, RP, Spillenaar Bilgen, EJ, Kouwenhoven, EA, de Wilt, JHW, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(6):4436-4443
Abstract
BACKGROUND & AIMS The inflammatory potential of the diet has been linked to colorectal cancer (CRC) development and mortality. However, it is unknown whether it is also associated with CRC recurrence. Therefore, the aim of this study was to investigate the associations between the inflammatory potential of the diet and plasma inflammation markers as well as recurrence and all-cause mortality in CRC patients. METHODS Data of the Colorectal cancer, Observational, LONgitudinal (COLON) study, a prospective cohort study, was used. Dietary intake, assessed using a semi-quantitative food frequency questionnaire, was available for 1478 patients at diagnosis and for 1334 patients six months after diagnosis. Dietary intake data were used to calculate the adapted dietary inflammatory index (ADII). Data about cancer recurrence and all-cause mortality, were assessed through linkage with the Netherlands Cancer Registry and the Municipal Personal Records Database, respectively. The association between the ADII (continuous) and inflammation markers (Interleukin (IL)6, IL8, IL10, Tumor Necrosis Factor (TNF)α, high sensitivity C-reactive protein (hsCRP) and a summary inflammatory z-score), measured with a multiplex assay using electrochemiluminiscence detection, was assessed using quantile regression analyses. Restricted cubic splines (RCS) analyses and multivariable Cox proportional hazard models were used to explore the relationship between the ADII and CRC outcomes. RESULTS During a median follow-up time of 3.2 years (Interquartile range (IQR) 2.0-4.1) for recurrence and 4.8 years (IQR 3.5-5.9) for all-cause mortality, 228 recurrences and 279 deaths occurred. A more pro-inflammatory diet at diagnosis as well as six months after diagnosis was associated with higher levels of TNFα, hsCRP and the summary inflammatory z-score. Results of RCS showed no relationship between the ADII and CRC outcomes at both time points. Also results of the Cox proportional hazard models showed no associations between the ADII at both time points and recurrence (HR (95%CI) 0.98 (0.94-1.04) & 0.96 (0.91-1.02) or all-cause mortality (HR (95%CI) 1.03 (0.98-1.07) & 1.00 (0.95-1.05)). CONCLUSION Our study did not show an association between the ADII and recurrence and all-cause mortality in CRC patients. Further research should also take into account molecular tumor subtypes, as the effect of the inflammatory potential of the diet on cancer recurrence and mortality is more likely to be present in tumors with an inflammatory signature. CLINICAL TRIAL REGISTRY NUMBERS AND WEBSITE The colon study: NCT03191110; clinical trials.gov.
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Relation of the Metabolic Syndrome to Incident Colorectal Cancer in Young Adults Aged 20 to 49 Years.
Jimba, T, Kaneko, H, Yano, Y, Itoh, H, Yotsumoto, H, Seki, H, Morita, K, Kiriyama, H, Kamon, T, Fujiu, K, et al
The American journal of cardiology. 2021;:132-138
Abstract
Onco-cardiology is the emerging field, and the concept of shared risk factor holds an important position in this field. The increasing prevalence of colorectal cancer (CRC) in young adults is a critical epidemiological issue. Although metabolic syndrome, which is a major risk factor for cardiovascular disease, is known to be associated with CRC incidence in middle-aged and elderly individuals, it is unclear whether this association is present in young adults. We assessed whether metabolic syndrome was associated with CRC events in young adults (aged <50 years), and whether the association differed by the definition of metabolic syndrome. We retrospectively analyzed 902,599 adults (20 to 49 years of age) enrolled in the JMDC Claims Database which is a nationwide epidemiological database in Japan between January 2005 and August 2018. Participants who had a history of CRC, colorectal polyps, or inflammatory bowel disease were excluded. Study participants were categorized into 2 groups according to the presence of metabolic syndrome, defined using the Japanese criteria (waist circumference ≥85 cm for men and ≥90 cm for women, and ≥2 metabolic parameters including elevated blood pressure, elevated triglycerides, reduced high-density lipoprotein cholesterol, or elevated fasting plasma glucose). Clinical outcomes were collected between January 2005 and August 2018. The primary outcome was CRC of any stage. Median (interquartile range) age was 41 (37 to 45), and 55.4% were men. Over a median follow-up of 1,008 (429 to 1,833) days, there were 1,884 incidences of CRC. After multivariable adjustment, the hazard ratio (HR) of metabolic syndrome for CRC events was 1.26 (95% confidence interval [CI] = 1.07 to 1.49). Cox regression analysis after multiple imputation for missing values showed that metabolic syndrome was associated with CRC incidence (HR = 1.35, 95% CI = 1.17 to 1.56). Metabolic syndrome was also associated with a higher incidence of CRC in individuals with a follow-up period of ≥365 days (HR = 1.33, 95% CI = 1.10 to 1.60). This association was observed when metabolic syndrome was defined according to the International Diabetes Federation criteria (HR = 1.30, 95% CI = 1.09 to 1.55) and the National Cholesterol Education Program Adult Treatment Panel III criteria (HR = 1.39, 95% CI = 1.12 to 1.72). In conclusion, metabolic syndrome was associated with a higher incidence of CRC among individuals aged <50 years. These results could be informative for risk stratification of subsequent CRC among young adults.
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Cumulative Burden of Colorectal Cancer-Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer.
Archambault, AN, Su, YR, Jeon, J, Thomas, M, Lin, Y, Conti, DV, Win, AK, Sakoda, LC, Lansdorp-Vogelaar, I, Peterse, EFP, et al
Gastroenterology. 2020;(5):1274-1286.e12
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Abstract
BACKGROUND & AIMS Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC. METHODS We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants. RESULTS Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10-5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings. CONCLUSIONS In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.
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Expression Patterns of Xenobiotic-Metabolizing Enzymes in Tumor and Adjacent Normal Mucosa Tissues among Patients with Colorectal Cancer: The ColoCare Study.
Beyerle, J, Holowatyj, AN, Haffa, M, Frei, E, Gigic, B, Schrotz-King, P, Boehm, J, Habermann, N, Stiborova, M, Scherer, D, et al
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2020;(2):460-469
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Abstract
BACKGROUND Xenobiotic-metabolizing enzymes (XME) play a critical role in the activation and detoxification of several carcinogens. However, the role of XMEs in colorectal carcinogenesis is unclear. METHODS We investigated the expression of XMEs in human colorectal tissues among patients with stage I-IV colorectal cancer (n = 71) from the ColoCare Study. Transcriptomic profiling using paired colorectal tumor and adjacent normal mucosa tissues of XMEs (GSTM1, GSTA1, UGT1A8, UGT1A10, CYP3A4, CYP2C9, GSTP1, and CYP2W1) by RNA microarray was compared using Wilcoxon rank-sum tests. We assessed associations between clinicopathologic, dietary, and lifestyle factors and XME expression with linear regression models. RESULTS GSTM1, GSTA1, UGT1A8, UGT1A10, and CYP3A4 were all statistically significantly downregulated in colorectal tumor relative to normal mucosa tissues (all P ≤ 0.03). Women had significantly higher expression of GSTM1 in normal tissues compared with men (β = 0.37, P = 0.02). By tumor site, CYP2C9 expression was lower in normal mucosa among patients with rectal cancer versus colon cancer cases (β = -0.21, P = 0.0005). Smokers demonstrated higher CYP2C9 expression levels in normal mucosa (β = 0.17, P = 0.02) when compared with nonsmokers. Individuals who used NSAIDs had higher GSTP1 tumor expression compared with non-NSAID users (β = 0.17, P = 0.03). Higher consumption of cooked vegetables (>1×/week) was associated with higher CYP3A4 expression in colorectal tumor tissues (β = 0.14, P = 0.007). CONCLUSIONS XMEs have lower expression in colorectal tumor relative to normal mucosa tissues and may modify colorectal carcinogenesis via associations with clinicopathologic, lifestyle, and dietary factors. IMPACT Better understanding into the role of drug-metabolizing enzymes in colorectal cancer may reveal biological differences that contribute to cancer development, as well as treatment response, leading to clinical implications in colorectal cancer prevention and management.
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Is aflibercept an optimal treatment for wt RAS mCRC patients after progression to first line containing anti-EGFR?
Vera, R, Mata, E, González, E, Juez, I, Alonso, V, Iranzo, P, Martínez, NP, López, C, Cabrera, JM, Safont, MJ, et al
International journal of colorectal disease. 2020;(4):739-746
Abstract
PURPOSE To determine the efficacy and safety data of aflibercept + FOLFIRI in wt RAS mCRC patients after progression to standard chemotherapy + anti-EGFR treatment. METHODS Retrospective, observational study in real life conducted in wt RAS mCRC patients treated with FOLFIRI-aflibercept after progression to standard first line chemotherapy + anti-EGFR treatment. RESULTS A total of 120 patients from 12 Spanish hospitals were enrolled. Median age is 60 years (62.5%/37.5%male/female). Primary tumor site is 24.1%/75.9% right/left-side colon, and 40.8% of patients had a prior resection. All patients had wild-type RAS tumors including 5% of patients with BRAF mutations and received anti-EGFR treatment. At the time aflibercept was initiated, ECOG PS is 0/1 in 96% of patients. Median number of FOLFIRI-aflibercept cycles is 12. Efficacy results: Overall response rate is 33%; progression-free survival (PFS) is 6.9 months (95%CI: 6.1-7.8). Primary tumor resection was the only significant variable related to PFS in the multivariate analysis. Median overall survival (OS) is 14.5 months (95%CI: 9.7-19.3). ECOG and number of metastatic sites were related to OS in multivariate analysis. About 54.1% of patients received a third-line therapy including TAS-102 (23%), regorafenib (18.5%), and capecitabine (9.2%). TOXICITY Grade 3-4 toxicities were observed in 37.5% of the patients (hematologic 16.6%, hypertension 7.5%, asthenia 5.9%, and perforation 2.5%). Aflibercept dose was reduced in 18.3% of patients. CONCLUSIONS The results show that patients with wt RAS mCRC who received an anti-EGFR as part of the first-line treatment achieved similar RR, PFS, OS, and toxicities to those reported in VELOUR trial. These results suggest that FOLFIRI-aflibercept after first-line treatment with anti-EGFR is an appropriated option for RAS wt mCRC.
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Promising results of a new treatment in patients with bowel obstruction in colorectal surgery.
Fahim, M, Dijksman, LM, van Kessel, CS, Smeeing, DPJ, Braaksma, A, Derksen, WJM, Smits, AB
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2020;(3):415-419
Abstract
INTRODUCTION Bowel obstruction increases risk of emergency surgery and leads to suboptimal physical and nutritional condition. Preventing emergency surgery and prehabilitation might improve outcomes. This pilot study aimed to examine the effect of a multimodal obstruction protocol for bowel obstruction patients on the risk of emergency surgery and postoperative morbidity and mortality. MATERIALS AND METHODS All bowel obstruction patients treated according to the obstruction protocol in the period 2013-2017 were included in this uncontrolled observational cohort study. Benign and malignant causes of bowel obstruction were included. The protocol consisted of: 1. specific dietary adjustments to reduce prestenotic dilatation, 2. oral laxatives and 3. prehabilitation. Emergency surgery and postoperative morbidity and mortality rates were compared to known rates from the literature. RESULTS Sixty-one patients were included: 44 (72%) were treated for colorectal cancer and 17 (28%) for Crohn's disease or diverticulitis. Four patients (7%) underwent emergency surgery. Primary anastomosis was constructed in 49 out of 57 elective patients (86%). Severe complications (Clavien-Dindo ≥ III) occurred in four patients (7%). No bowel perforation, anastomotic leakages or 30-day mortality was observed. These rates were much lower than rates reported in the literature after surgery for colorectal cancer (3% bowel perforation, 8% anastomotic leakage, 4% 30-day mortality, 15% severe complications) and benign disease (30-day mortality 17%, severe complications 7%). CONCLUSION Using the obstruction protocol in patients with bowel obstruction reduced emergency surgery and postoperative morbidity and mortality in this pilot study. This protocol seems to be a viable and efficient alternative to emergency surgery.