BACKGROUND & AIMS:

Patients with inflammatory bowel diseases (IBDs) (Crohn’s disease, ulcerative colitis) are at increased risk of colorectalcancer (CRC). Persistent inflammation is hypothesized to increase risk of CRC in patients with IBD; however, the few studies in this area have been restricted to cross-sectional assessments of histologic severity. No prior studies have examined association between C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) elevation and risk of CRC in an IBD cohort.

METHODS:

From a multi-institutional validated IBD cohort, we identified all patients with at least one measured CRP or ESR value. Patients were stratified into quartiles of severity of inflammation on the basis of their median CRP or ESR value, and subsequent diagnosis of CRC was ascertained. Logistic regression adjusting for potential confounders was used to identify the independent association between CRP or ESR elevation and risk of CRC.

RESULTS:

Our study included 3145 patients with at least 1 CRP value (CRP cohort) and 4008 with at least 1 ESR value (ESR cohort). Thirty-three patients in the CRP cohort and 102 patients in the ESR cohort developed CRC during a median follow-up of 5 years at a median age of 55 years. On multivariate analysis, there was a significant increase in risk of CRC across quartiles of CRP elevation (Ptrend = .017; odds ratio for quartile 4 vs quartile 1, 2.72; 95% confidence interval, 0.95-7.76). Similarly higher median ESR was also independently associated with risk of CRC across the quartiles (odds ratio, 2.06; 95% confidence interval, 1.14-3.74) (Ptrend = .007).

CONCLUSIONS:

An elevated CRP or ESR is associated with increased risk of CRC in patients with IBD.

Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and serum lactate dehydrogenase (LDH) are non-specific biochemical markers, accompanying the growth of some neoplasms, both in adults and in children. The aim of this study was to determine the clinical value of ESR, CRP and LDH evaluation in the diagnosis, prognosis and monitoring of treatment among children suffering from cancer. 100 children patients with acute leukaemia, Hodgkin’s and non-Hodgkin’s lymphoma, nephroblastoma and soft tissue sarcoma were included in the study, being compared to 30 healthy children of the control group. In oncological patients all the markers were estimated prospectively at 5 stages or the disease, i.e.: before treatment, during treatment — in partial remission (PR) and after complete clinical remission was achieved (CR), after therapy and during the relapse or progression of cancer (PROG). The mean pre-treatment levels of analysed markers in cancer patients were significantly higher than in healthy children (p<0.001). The elevation of ESR, CRP and LDH was observed in 78.7, 50.8 and 72.1% of cases respectively. Good clinical response to antitumour therapy was paralleled with the significant decrease of pre-treatment ESR, CRP and LDH levels, but the values observed in CR, both while treatment and after therapy, did not return towards normal range. The progression of disease was accompanied by the increase of ESR, CRP and LDH levels, however only ESR and CRP values differed significantly in PROG as compared to the CR phase. Among analysed markers, only LDH level at diagnosis proved to be an independent prognostic factor for the overall survival rate. Three-year overall survival rate for patients with pre-treatment LDH level <1.5 x normal value (N) was 94% while for those with LDH >1.5 x N — 67%. It has been demonstrated that ESR, CRP and LDH determinations in children suffering from cancer may serve as useful markers both in diagnostics and monitoring of the disease course. Moreover, the pre-treatment LDH level appeared to have an important role in prognosis of the overall survival rate.

Background: Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in American women. Post-surgery adjuvant radiotherapy (RT) significantly reduced the local recurrence rate. However, many patients develop early adverse skin reactions (EASRs) that impact quality of life and treatment outcomes. Methods: We evaluated an inflammatory biomarker, C-reactive protein (CRP) in predicting RT-induced EASRs in 159 breast cancer patients undergoing RT. In each patient, we measured pre- and post-RT plasma CRP levels using a highly-sensitive ELISA CRP assay. RT-induced EASRs were assessed at weeks 3 and 6 using the National Cancer Institute Common Toxicity Criteria (v3.0). Association between EASRs and CRP levels were assessed using logistic regression models after adjusting for potential confounders. Results: RT-induced grade 2+ EASRs were observed in 8 (5%) and 80 (50%) patients at weeks 3 and 6 (end of RT), respectively. At the end of RT, significantly higher proportion of African Americans developed grade 3 EASRs (13.8% vs. 2.3% in others); grade 2+ EASRs were significantly associated with: change of CRP>1 mg/L (OR=2.51; 95%CI=1.06, 5.95, p=0.04), obesity (OR=2.08; 95%CI=1.03, 4.21, p=0.04), or combined both factors (OR=5.21; 95%CI=1.77, 15.38, p=0.003). Conclusion: This is the first study to demonstrate that an inflammatory biomarker CRP is associated with RT-induced EASRs, particularly combined with obesity. Impact: Future larger studies are warranted to validate our findings and facilitate the discovery and development of anti-inflammatory agents to protect normal tissue from RT-induced adverse effects and improve quality of life in breast cancer patients undergoing RT.

BACKGROUND:

Inflammation may underlie cancer-related fatigue; however, there are no studies that assess the relation between fatigue and cytokines in patients with advanced disease versus patients without disease activity. Furthermore, the relation between cytokines and the separate dimensions of fatigue is unknown. Here, association of plasma levels of inflammatory markers with physical fatigue and mental fatigue was explored in advanced cancer patients and cancer survivors.

METHODS:

A total of 45 advanced cancer patients and 47 cancer survivors completed the subscales Physical Fatigue and Mental Fatigue of the Multidimensional Fatigue Inventory. Plasma concentrations of C-reactive protein (CRP), interleukin-1 receptor antagonist (IL-1-ra), interleukin-6 (IL-6), interleukin-8 (IL-8), and neopterin were measured. Nonparametric tests were used to assess differences in fatigue intensity and levels of inflammatory markers and to determine correlation coefficients between the fatigue dimensions and inflammatory markers.

RESULTS:

Compared with cancer survivors, patients with advanced cancer had higher levels of physical fatigue (median 16 vs 9, P < .001) and mental fatigue (median 11 vs 6, P = .01). They also had higher levels of all cytokines (P < .01). In advanced cancer, CRP (r = 0.49, P = .001), IL-6 (r = 0.43, P = .003), IL-1-ra (r = 0.32, P = .03), and neopterin (r = 0.25, P = .10) were correlated with physical but not with mental fatigue. In cancersurvivors, only IL-1-ra was related to both physical fatigue (r = 0.24, P = .10) and mental fatigue (r = 0.35, P = .02).

CONCLUSIONS:

In advanced cancer, inflammation seems to be associated with physical fatigue, but not to mental fatigue. In cancer survivors, there was no convincing evidence that inflammation plays a major role in fatigue.

TNF was originally described as a circulating factor that can cause necrosis of tumours, but has since been identified as a key regulator of the inflammatory response. This review describes the known signalling pathways and cell biological effects of TNF, and our understanding of the role of TNF in human disease. TNF interacts with two different receptors, designated TNFR1 and TNFR2, which are differentially expressed on cells and tissues and initiate both distinct and overlapping signal transduction pathways. These diverse signalling cascades lead to a range of cellular responses, which include cell death, survival, differentiation, proliferation and migration. Vascular endothelial cells respond to TNF by undergoing a number of pro-inflammatory changes, which increase leukocyte adhesion, transendothelial migration and vascular leak and promote thrombosis. The central role of TNF in inflammation has been demonstrated by the ability of agents that block the action of TNF to treat a range of inflammatory conditions, including rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease and psoriasis. The increased incidence of infection in patients receiving anti-TNF treatment has highlighted the physiological role of TNF in infectious diseases.

2007 Pathological Society of Great Britain and Ireland

TNF-alpha as a therapeutic target in inflammatory diseases, ischemia-reperfusion injury and trauma.