The prognostic role of baseline CEA and CA 19-9 values and their time-dependent variations in advanced colorectal cancer patients submitted to first-line therapy.

Serum marker evaluation is an easily available prognostic indicator that may help clinicians to discriminate patients with an aggressive disease; there are few and small-sized studies exploring the prognostic role of baseline carcinoembryonic antigen (CEA) values and their variations during first-line therapy, and even fewer data are available for carbohydrate antigen 19-9 (CA 19-9). Our aim was to analyze the role of those prognostic markers to exploit them in daily clinical practice. Data of 892 patients with marker determination before and 3 and/or 6 months during therapy were extracted from two institutional databases. Patients were grouped according to single marker variation as always negative (G0), decreasing (G1), stable (G2), or increasing (G3). We evaluated the progression-free survival (PFS) and the overall survival (OS) of all the patents and correlated them with CEA and CA 19-9 values. A concordance between response to therapy and marker decrease was evident in 50.2% and in 34.4% of the patients for CEA and CA 19-9. Patients with low CEA or CA 19-9 baseline values had a longer PFS (15.1 vs. 10.5; 13.6 vs. 10.2 months) and OS (32.0 vs. 22.3; 30.5 vs. 20.1 months). The same results of PFS and OS were obtained by analyzing the data of the four different groups. Multivariate analyses confirmed the independent prognostic role of CEA and CA 19-9. Baseline CEA and CA 19-9 levels and their kinetics demonstrated to be independent prognostic factors. CA 19-9 dosage is not recommended; a possible role of CA 19-9 in patients with negative CEA could be worth further evaluation

Progressive increase of matrix metalloprotease-9 and interleukin-8 serum levels during carcinogenic process in human colorectal tract

BACKGROUND: Inflammatory reactions, known to promote tumor growth and invasion, have been found associated with colorectal carcinoma (CRC). Macrophages are the chief component of the inflammatory infiltration that occurs early in the progression from non-invasive to malignant tumor, with a switch from the pro-inflammatory phenotype to the tumor-promoting phenotype. Tumor and stroma are additional sources of inflammation-related molecules. The study aimed to evaluate, during colorectal carcinogenesis from benign to malignant phases: i) the trend of serum levels of IL-8, IL-6, TGFβ1, VEGF and MMPs; ii) the parallel trend of CRP serum levels; iii) derangement of the principal TGFβ1 receptors (TGFβ1RI/RII) in tumor tissues. METHODOLOGY/PRINCIPAL FINDINGS: 96 patients with colon adenomas or CRC at different stages of progression, and 17 controls, were recruited. Serum IL-8, IL-6, TGFβ1, VEGF, MMPs and CRP levels were analyzed before endoscopy or surgery. TGFβ1 receptors were evaluated in adenoma biopsies and surgically-removed colorectal adenocarcinomas. Serum levels of IL-8 in adenocarcinoma patients were increased from stage II, when also the enzymatic activity of MMP-9 increased. Of note, the increasing trend of the two serum markers was found significantly correlated. Trend of serum CRP was also very similar to that of IL-8 and MMP-9, but just below statistical significance. TGFβ1 levels were lower at stage III CRC, while IL-6 and VEGF levels had no significant variations. In tissue specimens, TGFβ1 receptors were already absent in about 50% of adenomas, and this percentage of missing receptors markedly increased in CRC stages III and IV. CONCLUSIONS: Combined quantification of serum IL-8, MMP-9 and CRP, appears a reliable and advanced index of inflammation-related processes during malignant phase of colorectal carcinogenesis, since these molecules remain within normal range in colorectal adenoma bearing patients, while consistently increase in the blood of CRC patients, even if from stage II only

Il Progetto Innovativo TR65 Budget di salute dell'ASST Pavia

L'articolo descrive, analizza e modelizza l'esperienza sviluppata nel territorio della provincia di Pavia il modello operativo del budget di salute, considerando e rimodulando l'insieme delle risorse economiche, umane, professionali e terapeutiche messe a disposizione delle persone con severi problemi di salute mentale, secondo una prospettiva "recovery oriented

An exploratory analysis of the association between levels of hormones implied in steroid biosynthesis and activity of abiraterone in patients with metastatic castration-resistant prostate cancer.

BACKGROUND: Abiraterone acetate, approved for patients with metastatic castration-resistant prostate cancer (mCRPC), blocks androgen byosinthesis. We aimed to describe changes determined by abiraterone in hormones implied in steroid biosynthesis, exploring association between hormonal levels and drug activity. METHODS: Patients with mCRPC, receiving standard abiraterone + prednisone after docetaxel failure, were studied. We determined serum levels of progesterone, 17OH-progesterone, cortisol, ACTH, DHEA-sulphate, androstenedione, testosterone, sex hormone-binding globulin, aldosterone, plasma renin activity, and cholesterol, baseline and every 12 weeks. For each hormone, association with treatment activity was tested (1) comparing baseline values in responders vs. non-responders; (2) comparing progression-free survival (PFS) of patients with baseline low vs. high values; (3) comparing values after 12 weeks in responders vs. non-responders. RESULTS: 49 patients were analyzed; 26 patients (53.1%) experienced PSA response. Baseline values of all hormones were not statistically different between responders and non-responders. For all hormones, PFS difference of patients with low vs. high baseline values was not statistically significant. Several hormones showed significant and sustained changes vs. baseline, but all significant changes were similar between responders and non-responders. CONCLUSIONS: This analysis does not suggest a significant association between baseline hormonal values, or changes induced by abiraterone, and treatment activity