An epidemiology-based model to estimate the rate of inappropriateness of tumor marker requests.

BACKGROUND: Appropriateness of tumor markers (TMs) has been retrospectively studied in limited patients' series, matching the requests to clinical records. Methods to monitor appropriateness suitable for use on a large scale are required. This study aims to establish and validate an innovative model to estimate appropriateness based on the comparison between the number of TMs requested and the expected requests inferred from epidemiological data. METHODS: The number of CA15.3, CA19.9 and CA125 requests theoretically expected according to the epidemiology of malignancies in a known geographic area (2 Italian regions) was compared with the number of TMs actually requested - the surveyed requests projected on a regional scale - during a given time span (1 year). The expected number of requests was calculated comparing TMs recommended by guidelines in different clinical scenarios with the prevalence or incidence figures of the examined diseases (carcinomas of breast, pancreas and biliary tract, ovary and endometrium). RESULTS: Suitability of the model was demonstrated with the analysis of 1,891,070 TM requests surveyed in 66 laboratories from Veneto and Tuscany regions. The percentage difference over the total of expected TMs (delta%) ranged from -6.9% for CA15.3 to +1022.6% for CA19.9 in Veneto and from +35.7% for CA15.3 to +1842.6% for CA19.9 in Tuscany. CONCLUSIONS: The presented model was effective in demonstrating higher than expected TM request rates, possibly associated with inappropriate use. Moreover, it can be applied on a large scale survey setting since it circumvents the unavailability of clinical information on test orders.

BTK: 22 novel and 25 recurrent mutations in European patients with X-linked agammaglobulinemia.

X linked agammaglobulinemia (XLA) is an immunodeficiency disease caused by mutations in the gene coding for Bruton's agammaglobulinemia tyrosine kinase (BTK), that is involved in signal transduction pathways regulating survival, activation, proliferation, and differentiation of B lineage lymphoid cells. XLA is a primary immunodeficiency disorder characterized by lack of mature, circulating B lymphocytes, and recurrent infections. Using Single Strand Conformation Polymorphism (SSCP) followed by direct sequencing we investigated 57 patients with XLA phenotype, with or without a positive family history, from 52 unrelated families enrolled in the Italian XLA Multicenter Clinical Study. We have identified 25 recurrent mutations, 22 novel mutations including one large deletion comprising the coding sequence from exon 11 to 18. Among the mutations identified, three were detected in different unrelated families, whereas all the others were private mutations.

Prognostic significance of vascular endothelial growth factor serum determination in women with ovarian cancer.

Introduction. We performed a review of the literature to elucidate the potential prognostic significance of serum vascular endothelial growth factor (sVEGF) levels in ovarian cancer. Methods. Eligible studies in English and Italian were identified in MEDLINE/PubMed from VEGF discovery to October 2011. All studies evaluating: (i) sVEGF levels before any surgical and chemotherapeutic treatment; (ii) the association between sVEGF levels and the established prognostic variables; (iii) the value of sVEGF levels in predicting patients' outcomes, were selected for this review. Results. The search resulted in 758 titles. Nine studies met the inclusion criteria. A statistically significant association between the level of sVEGF and FIGO stage, tumour grade, residual tumour size, lymph node involvement, and presence of ascites was found in at least one study. sVEGF, in comparison with the established prognostic factors, appears to be the best prognostic marker for overall survival, since it stands out as an independent prognostic factor in most of the studies considered. Moreover, sVEGF levels were shown to be independent prognostic factors by 2 out of the 3 studies that considered DFS as an end point. Conclusion. High levels of sVEGF identify a subgroup of patients with higher risk of death and/or recurrence. These patients should be eligible for individually tailored therapeutic interventions.

Tumour markers requesting pattern with regards to different organizational settings in Italy: a survey of hospital laboratories.

BACKGROUND: Tumour markers are frequently used in clinical practice and the reason for ordering varies considerably and often seems to be inappropriate. We carried out a survey of Italian laboratories on their current pattern of use. METHODS: Forty-four laboratories located in health-care institutions with inpatient beds were surveyed about the organizational, clinical and methodological aspects of tumour markers ordering. RESULTS: Thirty-one laboratories (70%) filled in and returned the questionnaire. Overall, 977,786 tumour marker tests were scrutinized. The pattern of tumour marker use did not seem to be influenced by the institutional setting, by availability of oncology facilities or by adoption of clinical guidelines. In addition, the information flow from clinicians to the laboratory and vice versa was poor and informal. CONCLUSIONS: Monitoring tumour marker pattern use can provide valuable information for health-care decision makers, highlighting potential inadequacies in laboratory services but also identifying problems in other areas of health-care delivery that could benefit from educational programmes.