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LE Magazine February 2001

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Acute-phase protein response and survival duration of patients with pancreatic cancer

BACKGROUND. Current methods to predict survival duration of patients with pancreatic cancer are limited. The aim of this study was to determine whether certain nutritional indices and the acute-phase protein response are prognostic factors independent of disease stage for patients with unresectable pancreatic cancer. METHODS. Variables at the time of diagnosis of 102 patients with unresectable pancreatic cancer were entered into a Cox's proportional hazards model. Included in the analysis were the serum concentration of C-reactive protein (CRP) and albumin, the extent of weight loss, age, sex, and disease stage (International Union Against Cancer criteria). RESULTS. A multivariate analysis in which each factor was adjusted for the influence of the other factors revealed the patient age, disease stage, serum albumin, and serum CRP to be independent predictors of survival. The presence of an acute-phase protein response was the most significant independent predictors of survival duration. The median survival of those with an acute-phase protein response (CRP > 10 mg/L, n = 45) was 66 days compared with 222 days for those with no acute-phase protein response (n = 57, P = 0.001, Mann-Whitney U test). CONCLUSION. The acute-phase protein response is a useful prognostic indicator for patients with unresectable pancreatic cancer. Moreover, the metabolic disturbances associated with an acute-phase protein response of patients with pancreatic cancer may be a worthwhile therapeutic target.

Cancer 1995 Apr 15;75(8):2077-82

A prospective study of tumor recurrence and the acute-phase response after apparently curative colorectal cancer surgery

BACKGROUND: Approximately 70% of patients who are going to develop tumor recurrence following curative colorectal surgery do so within 24 months of surgery. PATIENTS AND METHODS: The relationship was prospectively examined between an ongoing acute-phase response and subsequent clinical relapse in 36 colorectal cancer patients who had undergone a curative resection. Approximately 4 months after their operation, patients were grouped according to the presence (n = 15) or absence (n = 21) of an acute-phase response (C-reactive protein > 5 mg/L) and were followed-up for a minimum of 24 months. RESULTS: Age, tumor site, and serum carcinoembryonic antigen concentrations were similar in both groups. There was a significantly higher recurrence rate in patients with an acute-phase response (11 of 15) compared to those with no acute-phase response (2 of 21, P < 0.01). CONCLUSIONS: These results are consistent with the presence of an acute-phase response being an important predictive factor in the early stages of tumor recurrence in patients who have had apparently curative colorectal surgery.

Am J Surg 1995 Oct;170(4):319-22

Malnutrition and wasting, immunodepression, and chronic inflammation as independent predictors of survival in HIV-infected patients

To analyze the long-term survival factors associated with HIV infection, a prospective follow-up study of 165 HIV-infected patients was performed after a clinical, nutritional, and biological evaluation. Survival rate could be determined in 129 patients after a follow-up of 42 mo before the use of protease inhibitors. After univariate analysis, multivariate analysis was performed with the Cox regression proportional-hazard model. Survival curves were calculated and compared with the Kaplan, Meier, and log-rank tests. The study also analyzed the factors associated with impaired nutritional status at the beginning of the study and their effects on the long-term follow-up. Factors that could explain body weight loss before the study were the level of intakes, resting energy expenditure, chronic diarrhea, and the number of previous opportunistic infections. In the long-term follow-up, univariate analysis showed that nutritional status could be separated into four classes of body weight loss (BWL) by degree of loss (BWL < or = 5%, 5% < BWL < or = 10%, 10% < BWL < or = 20%, BWL > 20%); lean body mass (adjusted to height), body cell mass, CD4 count, albumin, prealbumin, and C-reactive protein (CRP) were all significant predictors. Age, stage of disease, number of previous opportunistic infections, and antiviral therapies were not associated with a change in survival. With the multivariate model, only CD4 counts, lean body mass/height squared, and CRP remained significant independent predictors of survival after controlling for other factors.

Nutrition 1999 Nov-Dec;15(11-12):865-9

Extent of inflammation predicts cardiovascular disease and overall mortality in seropositive rheumatoid arthritis - A retrospective cohort study from disease onset

OBJECTIVE: To identify predictors for cardiovascular disease (CVD) and for overall survival in patients with rheumatoid arthritis (RA) followed from disease onset. METHODS: A retrospective cohort of patients with seropositive RA and disease onset between 1974 and 1978 (n = 211) was followed up at the end of 1995. Potential predictors for CVD, as measured by "the first cardiovascular event," and for overall survival were registered. The predictors were identified by extended Cox regression models. RESULTS: In simple Cox regression analysis, male sex, higher age at disease onset, HLA-B27, high disease activity, corticosteroid treatment early in disease, and hypertension significantly increased risk of cardiovascular event. Higher educational level, extensive disease modifying antirheumatic drug (DMARD) treatment, and corticosteroids > or =1 yr before event decreased the risk. In multiple Cox regression analysis, male sex, high age at disease onset, hypertension, higher haptoglobin level at disease onset, and corticosteroid treatment early in disease increased risk of CVD. In a multiple model comprising only patients with CVD, corticosteroids delayed the event. A high last registered erythrocyte sedimentation rate (ESR) value before event increased CVD risk, in particular when early in disease progression. Decreased life span was predicted by higher age at disease onset, male sex, low education level, high disease activity, hypertension, and CVD. HLA-B27 was associated with decreased life span, as was early, but not extensive corticosteroid treatment. DMARD treatment was associated with decreased mortality risk, as was the presence of joint prosthesis. In multiple regression, male sex, higher age at disease onset, atlantoaxial subluxation early in disease, hypertension, and cardiovascular event increased mortality. A high last registered ESR value before event or death added to that risk. CONCLUSION: The study emphasizes the importance of inflammation as an important risk indicator for CVD and mortality in RA. The positive impact of disease activity reducing treatment on CVD risk and survival is suggested.

J Rheumatol 1999 Dec;26(12):2562-71

Changes in micronutrient concentrations following anti-inflammatory treatment in patients with gastrointestinal cancer

Circulating concentrations of vitamin antioxidants (retinol, alpha-tocopherol, lutein, lycopene, alpha- and beta-carotene) and trace elements (zinc, copper, iron and selenium) plus carrier proteins (albumin, transferrin, caeruloplasmin) in gastrointestinal cancer patients (n = 12) with an inflammatory response (as demonstrated by an elevated C-reactive protein concentration) were compared with a control group (n = 12). Further, the effect of moderating the inflammatory response, using the anti-inflammatory agent ibuprofen, on these measurements was examined in the cancer group. The control and cancer groups were similar in terms of age, sex, and body mass index. However, the cancer group had significantly higher C-reactive protein concentrations (P < 0.001). Concentrations of vitamin antioxidants and trace elements (and carrier proteins) were significantly lower (P < 0.001), except copper (ceruloplasmin) which was significantly higher (P < 0.05). After anti-inflammatory treatment, there were small but significant increases in lutein, lycopene, and beta-carotene (P < 0.05) and in iron and selenium (P < 0.05), whereas ceruloplasmin decreased (P < 0. 05). The micronutrient concentrations in the cancer patients remained different from those in the control subjects. These results support the concept that the magnitude of inflammation plays an important role in the regulation of circulating concentrations of vitamin antioxidants and trace elements in patients with gastrointestinal cancer.

Nutrition 2000 Jun;16(6):425-8

Demonstration of CRP immunoreactivity in brains of Alzheimer's disease: immunohistochemical study using formic acid pretreatment of tissue sections

C-reactive protein (CRP) is a well-known serum protein which increases during inflammation and deposits in damaged tissues. To establish whether CRP appears in brain of Alzheimer's disease (AD), we immunohistochemically investigated tissue sections which were pretreated with formic acid. Positive immunostaining by anti-CRP antibodies was clearly recognized in senile plaques (SP) in the pretreated tissue sections, with very weak immunostaining in non-treated sections. These findings may suggest that the formation process of SP includes an acute-phase inflammatory state.

Neurosci Lett 1994 Aug 15;177(1-2):23-6

Prediction of male cancer mortality by plasma levels of interacting vitamins: 17-year follow-up of the prospective Basel study

Plasma vitamins C, E, retinol and carotene were measured in 1971-1973 in 2,974 men working in Basel Switzerland. In 1990, the vital status of all participants was assessed. A total of 290 men had died from cancer during the 17 years of follow-up, including 87 with lung cancer, 30 with prostate cancer, 28 with stomach cancer and 22 with colon cancer. Overall mortality from cancer was associated with low mean plasma levels of carotene (adjusted for cholesterol) and of vitamin C. Lung and stomach cancers were associated with low mean plasma carotene level. After calculation of the relative risk, using the Cox model, with exclusion of mortality during the first 2 years of follow-up, simultaneously low levels of plasma carotene (below quartile I) and lipid-adjusted retinol were related to a significantly increased mortality risk for all cancers and for lung cancer. Simultaneously, low levels of plasma vitamin C and lipid-adjusted vitamin E also were associated with a significantly increased risk for lung cancer. Additionally, low vitamin E levels in smokers were related to an increased risk for prostate cancer. It is concluded that low plasma levels of the vitamins C, E, retinol and carotene are related to increased risk of subsequent overall and lung-cancer mortality and that low levels of vitamin E in smokers are related to an increased risk of prostate-cancer mortality.

Int J Cancer 1996 Apr 10;66(2):145-50

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