Several bacterial species have been implicated in the development of colorectal carcinoma (CRC), but CRC‐associated changes of fecal microbiota and their potential for cancer screening remain to be ...explored. Here, we used metagenomic sequencing of fecal samples to identify taxonomic markers that distinguished CRC patients from tumor‐free controls in a study population of 156 participants. Accuracy of metagenomic CRC detection was similar to the standard fecal occult blood test (FOBT) and when both approaches were combined, sensitivity improved > 45% relative to the FOBT, while maintaining its specificity. Accuracy of metagenomic CRC detection did not differ significantly between early‐ and late‐stage cancer and could be validated in independent patient and control populations (N = 335) from different countries. CRC‐associated changes in the fecal microbiome at least partially reflected microbial community composition at the tumor itself, indicating that observed gene pool differences may reveal tumor‐related host–microbe interactions. Indeed, we deduced a metabolic shift from fiber degradation in controls to utilization of host carbohydrates and amino acids in CRC patients, accompanied by an increase of lipopolysaccharide metabolism.
Synopsis
Metagenomic profiling of fecal samples from colorectal cancer (CRC) patients in comparison with tumor‐free controls reveals strong associations between the gut microbiota and cancer. Their potential for noninvasive cancer screening is explored systematically.
A classification model based on gut microbial marker species distinguishes CRC patients from controls with similar accuracy as the fecal occult blood test (FOBT), routinely used for clinical screening.
Combining metagenomic data with the FOBT leads to a relative improvement in sensitivity of > 45% over the FOBT alone at identical specificity.
Detection accuracy of the metagenomic test is maintained in an independent study population and is still high for alternative microbiome readouts, such as the abundance of 16S rRNA OTUs or families of functionally related genes.
Functional metagenomic analysis indicates an increased potential of CRC‐associated microbiota for degradation of host glycans and amino acids and for pro‐inflammatory lipopolysaccharide metabolism.
Metagenomic profiling of fecal samples from colorectal cancer (CRC) patients in comparison with tumor‐free controls reveals strong associations between the gut microbiota and cancer. Their potential for noninvasive cancer screening is explored systematically.
Metabolic and transcriptomic differences between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) compartments, particularly in the context of obesity, may play a role in ...colorectal carcinogenesis. We investigated the differential functions of their metabolic compositions.
Biochemical differences between adipose tissues (VAT compared with SAT) in patients with colorectal carcinoma (CRC) were investigated by using mass spectrometry metabolomics and gene expression profiling. Metabolite compositions were compared between VAT, SAT, and serum metabolites. The relation between patients' tumor stage and metabolic profiles was assessed.
Presurgery blood and paired VAT and SAT samples during tumor surgery were obtained from 59 CRC patients (tumor stages I-IV) of the ColoCare cohort. Gas chromatography time-of-flight mass spectrometry and liquid chromatography quadrupole time-of-flight mass spectrometry were used to measure 1065 metabolites in adipose tissue (333 identified compounds) and 1810 metabolites in serum (467 identified compounds). Adipose tissue gene expression was measured by using Illumina's HumanHT-12 Expression BeadChips.
Compared with SAT, VAT displayed elevated markers of inflammatory lipid metabolism, free arachidonic acid, phospholipases (PLA2G10), and prostaglandin synthesis-related enzymes (PTGD/PTGS2S). Plasmalogen concentrations were lower in VAT than in SAT, which was supported by lower gene expression of FAR1, the rate-limiting enzyme for ether-lipid synthesis in VAT. Serum sphingomyelin concentrations were inversely correlated (P = 0.0001) with SAT adipose triglycerides. Logistic regression identified lipids in patients' adipose tissues, which were associated with CRC tumor stage.
As one of the first studies, we comprehensively assessed differences in metabolic, lipidomic, and transcriptomic profiles between paired human VAT and SAT and their association with CRC tumor stage. We identified markers of inflammation in VAT, which supports prior evidence regarding the role of visceral adiposity and cancer.
Introduction
Mechanical circulatory support (MCS) devices are increasingly used as a treatment option in resuscitation or in patients with cardiogenic shock (CS). Prophylactic implantation in ...high‐risk percutaneous coronary interventions (HRPCI) is another upcoming indication. The i‐cor ECG‐synchronized cardiac assist device combines the hemodynamic support of a veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) with the ability to generate a pulsatile flow and thus decreasing adverse effects of VA‐ECMO on myocardial function. Aim of this study was to obtain data concerning feasibility, safety and outcomes in both indications.
Methods
A total of 47 patients (34 HRPCI, 13 CS) were included in nine German centers and participated in this study. Demographic and clinical parameters, procedural as well as follow‐up data were prospectively recorded and analyzed.
Results
Device implantation and initiation of ECG‐synchronized cardiac assist was technical successful in all cases and no failures of the consoles or disposable parts were observed. Furthermore, intended percutaneous coronary interventions and successful weaning from cardiac assist was achieved in 97.1% of HRPCI patients. We observed a 30d‐survival of 94.1% in the HRPCI group and 69.2% in the CS group. Main complications in both groups were bleeding events (14.7% HRPCI, 23.1% CS) and critical limb ischemia (2.9% HRPCI, 38.5% CS).
Conclusion
The i‐cor ECG‐synchronized cardiac assist device appears safe and feasible showing clinical outcomes comparable to existing data in the setting of high‐risk percutaneous coronary interventions and acute cardiogenic shock. Further prospective trials are warranted to identify optimal patient and interventional characteristics that will benefit most of this novel kind of mechanical circulatory support.
ECG‐synchronized cardiac assist combines the potent hemodynamic support with the ability of decreasing well described adverse effects on myocardial function of veno‐arterial extracorporeal membrane oxygenation. Forty seven patients 34 high‐risk percutaneous coronary interventions (HRPCI), 13 cardiogenic shock (CS) were included to obtain data concerning feasibility, safety and outcomes in both indications. The i‐cor ECG‐synchronized cardiac assist device appears safe and feasible. It is associated with short‐term clinical outcomes comparable to existing literature in the setting of HRPCI and acute CS.
Colorectal cancer is a leading cause of cancer death. Biomarkers to predict treatment outcomes are needed, as is evidence whether postdiagnosis diet and lifestyle can affect well-being and clinical ...outcomes. The international ColoCare Consortium aims to identify new biologic markers (e.g., metabolomic, transcriptomic, metagenomic, genetic, epigenetic, proteomic markers) that predict clinical outcomes, and to characterize associations between modifiable risk factors (e.g., diet, supplement use, physical activity) with short-term and long-term patient-reported and clinical outcomes among patients with colorectal cancer.
ColoCare is recruiting newly diagnosed patients with colorectal cancer across six sites in the United States and one site in Germany. As of April 2018, we have recruited >2,000 patients across all sites. Our projected enrollment is >4,000 multiethnic patients with colorectal cancer. The study includes uniformly collected, comprehensive sets of data and biospecimens at multiple time points up to 5 years after diagnosis. Treatment and clinical data are abstracted from medical records and centrally harmonized. Biospecimens are archived according to standardized procedures. Our initial studies demonstrated metabolic differences in adipose tissue types. We further reported on associations of biological factors (e.g., inflammation, DNA methylation, metabolomics) with lifestyle factors (e.g., adiposity, smoking, physical activity, dietary supplement use) or joint associations with clinical outcomes.
ColoCare is a consortium for the investigation of multilevel factors relevant to colorectal cancer survivorship.
The combination of a comprehensive set of biospecimens collected at multiple time points, jointly with detailed assessments of health behaviors and other prognostic factors, results in a unique resource that facilitates wide-ranging, innovative, and impactful research on colorectal cancer.
Purpose
Underlying mechanisms of the relationship between body fatness and colorectal cancer remain unclear. This study investigated associations of circulating metabolites with visceral (VFA), ...abdominal subcutaneous (SFA), and total fat area (TFA) in colorectal cancer patients.
Methods
Pre-surgery plasma samples from 212 patients (stage I–IV) from the ColoCare Study were used to perform targeted metabolomics. VFA, SFA, and TFA were quantified by computed tomography scans. Partial correlation and linear regression analyses of VFA, SFA, and TFA with metabolites were computed and corrected for multiple testing. Cox proportional hazards were used to assess 2-year survival.
Results
In patients with metastatic tumors, SFA and TFA were statistically significantly inversely associated with 16 glycerophospholipids (SFA:
p
FDR
range 0.017–0.049; TFA:
p
FDR
range 0.029–0.048), while VFA was not. Doubling of ten of the aforementioned glycerophospholipids was associated with increased risk of death in patients with metastatic tumors, but not in patients with non-metastatic tumors (p
het
range: 0.00044–0.049). Doubling of PC ae C34:0 was associated with ninefold increased risk of death in metastatic tumors (Hazard Ratio HR, 9.05; 95% confidence interval CI 2.17–37.80); an inverse association was observed in non-metastatic tumors (HR 0.17; 95% CI 0.04–0.87;
p
het
= 0.00044).
Conclusion
These data provide initial evidence that glycerophospholipids in metastatic colorectal cancer are uniquely associated with subcutaneous adiposity, and may impact overall survival.
Plasma microRNAs (miRNAs) are promising non-invasive biomarkers for colorectal cancer (CRC) prognosis. However, the published studies to date have yielded conflicting and inconsistent results for ...specific plasma miRNAs.
We have conducted a study using robust assays to assess a panel of nine miRNAs for CRC prognosis and early detection of recurrence. Plasma samples from 144 patients in a prospective CRC cohort study were collected at diagnosis, 6, 12, and 24 months after diagnosis. miRNAs were assayed by Taqman qRT-PCR to generate miRNA normalised copy numbers.
Preoperative high plasma miRNA levels were associated with increased recurrence risk for miR-200b (HR 95% CI=2.04 1.00, 4.16, P=0.05), miR-203 (HR=4.2 1.48, 11.93, P=0.007), miR-29a (HR=2.61 1.34,5.07, P=0.005), and miR-31 (HR=4.03 1.76, 9.24, P=0.001). Both plasma miR-31 (AUC: 0.717) and miR-29a (AUC: 0.703) could discriminate recurrence from these patients without recurrence. In addition, high levels of miR-31 during surveillance was associated with a three-fold increased risk of recurrence across all time points. Dynamic postoperative plasma miR-141 and 16 levels correlated with recurrence in the surveillance samples.
Pre-operative plasma miR-29a, 200b, 203, and 31 are potential CRC prognosis biomarkers. In addition, dynamic postoperative miR-31, 141 and 16 levels are potential biomarkers for the early detection of recurrence during CRC surveillance.
Quality of life (QoL) is an important clinical outcome in cancer patients. We investigated associations between dietary patterns and QoL changes in colorectal cancer (CRC) patients. The study ...included 192 CRC patients with available EORTC QLQ-C30 data before and 12 months post-surgery and food frequency questionnaire data at 12 months post-surgery. Principal component analysis was used to identify dietary patterns. Multivariate regression models assessed associations between dietary patterns and QoL changes over time. We identified four major dietary patterns: "Western" dietary pattern characterized by high consumption of potatoes, red and processed meat, poultry, and cakes, "fruit&vegetable" pattern: high intake of vegetables, fruits, vegetable oils, and soy products, "bread&butter" pattern: high intake of bread, butter and margarine, and "high-carb" pattern: high consumption of pasta, grains, nonalcoholic beverages, sauces and condiments. Patients following a "Western" diet had lower chances to improve in physical functioning (OR = 0.45 0.21-0.99), constipation (OR = 0.30 0.13-0.72) and diarrhea (OR: 0.44 0.20-0.98) over time. Patients following a "fruit&vegetable" diet showed improving diarrhea scores (OR: 2.52 1.21-5.34. A "Western" dietary pattern after surgery is inversely associated with QoL in CRC patients, whereas a diet rich in fruits and vegetables may be beneficial for patients' QoL over time.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Physical activity plays an important role in colorectal cancer and accelerometry is more frequently used to measure physical activity. The aim of this study was to evaluate feasibility of physical ...activity measurement by accelerometry in colorectal cancer patients under free-living conditions at 6, 12 and 24 months after surgery, to evaluate the appropriate wear time and to compare results to pedometry.
Colorectal cancer patients (stage 0/I-IV) from the ColoCare study were asked to optionally wear an accelerometer and a pedometer for ten consecutive days 6, 12 and 24 months post-surgery. Participants completed a feedback questionnaire about the accelerometer measurement. The course of moderate-to-vigorous physical activity over the 10 days was investigated. Additionally, daily step counts from accelerometers and pedometers were compared.
In total, there were 317 individual time points, at which 198 participants were asked to wear an accelerometer. Fifty-nine% initially agreed to participate and of these, 83% (n = 156) completed the assessment with at least 4 days of data. Twenty-one% more consents were obtained when participants were asked on a face-to-face basis compared to recruitment by telephone (P = 0.0002). There were no significant differences in time spent in moderate-to-vigorous physical activity between different wear-time lengths of accelerometry. Both Spearman and intraclass correlation coefficients showed strong correlations (0.92-0.99 and 0.84-0.99, respectively) of moderate-to-vigorous physical activity across 3, 4, 7 and 10 days measurement. Step counts measured by accelerometry and pedometry were strongly correlated (ρ = 0.91, P < 0.0001).
This study suggest that accelerometry is a feasible method to assess physical activity in free-living colorectal cancer patients and that three valid days of physical activity measurement are sufficient for an accurate assessment.
Obesity, defined by body mass index (BMI), measured at colorectal cancer (CRC) diagnosis has been associated with postoperative complications and survival outcomes. However, BMI does not allow for a ...differentiation between fat and muscle mass. Computed tomography (CT)-defined body composition more accurately reflects different types of tissue and their associations with health-related quality of life (HRQoL) during the first year of disease, but this has not been investigated yet. We studied the role of visceral and subcutaneous fat area (VFA and SFA) and skeletal muscle mass (SMM) on longitudinally assessed HRQoL in CRC patients.
A total of 138 newly diagnosed CRC patients underwent CT scans at diagnosis and completed questionnaires prior to and six and twelve months post-surgery. We investigated the associations of VFA, SFA, and SMM with HRQoL at multiple time points.
A higher VFA was associated with increased pain six and twelve months post-surgery (β = 0.06,
= 0.04 and β = 0.07,
= 0.01) and with worse social functioning six months post-surgery (β = -0.08,
= 0.01). Higher SMM was associated with increased pain twelve months post-surgery (β = 1.03,
< 0.01).
CT-quantified body composition is associated with HRQoL scales post-surgery. Intervention strategies targeting a reduction in VFA and maintaining SMM might improve HRQoL in CRC patients during the first year post-surgery.
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