Maria Stella Graziani

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Davide Giavarina
Bruna Lo Sasso
Giampaolo Merlini
Martina Montagnana
Andrea Mosca
Paola Pezzati
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Matteo Vidali

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BC: Articoli scritti da S. Ferraro

Il futuro della Medicina di Laboratorio
The future of Laboratory Medicine
Biochimica Clinica ; 40(2) 075-077
Editoriale - Editorial
Caratteristiche biochimiche e funzionali della proteina 4 dell’epididimo umano (HE4)
Biochemical and functional characteristics of human epididymis protein 4 (HE4)
<p>Serum carbohydrate antigen&nbsp;125 (CA125) is the established biomarker for detecting ovarian cancer (OC) recurrence and monitoring therapeutic&nbsp;response. The recent evidence calls into question the better performance of serum HE4 to detect patients with OC.&nbsp;The replacement of CA125 with HE4 appears advisable, but more focus is needed on the biochemical&nbsp;characterization of the protein structure, which is an overriding prerequisite to overcome possible methodological&nbsp;limitations. By resorting to published literature, we sought to review the available information on the protein structure,&nbsp;activity, functions and tissue expression under physiologic and pathologic conditions. The gene encoding for HE4,&nbsp;WFDC2, is composed by six exons. Five HE4 isoforms have been identified and recognized to define specific&nbsp;patterns differently expressed in neoplasm and normal tissues. Under physiologic conditions, HE4 is reported as&nbsp;protease inhibitor playing a crucial role in sperm maturation. In pathophysiology, HE4 is likely involved in cancer&nbsp;progression and metastases. In particular, HE4 is overexpressed in serous and endometrioid OC. Further information&nbsp;on the HE4 expression pattern in cancer progression will likely improve the clinical performance of the marker.</p>
Biochimica Clinica ; 38(5) 368-373
Rassegne - Reviews
Determinazione della vitamina B12 nel siero: indicazioni per la richiesta e l’interpretazione dei risultati
Determination of vitamin B12 in serum: recommendations for test request and result interpretation
S. Ferraro  |  A. Dolci  |  R. Mozzi  |  M. Panteghini  | 
<p>The&nbsp;measurement of vitamin B<sub>12</sub> (B12) in serum has an overall poor capability to rule out subjects for B12 deficiency.&nbsp;Furthermore, trying to identify those subjects by resorting to one solely test threshold level (e.g., the lower reference&nbsp;limit) may mislead the clinical diagnosis. Clinical laboratories should therefore optimize the test interpretation by&nbsp;replacing in their report the standard reference interval with a categorization of risk for B12 deficiency. Accordingly, a&nbsp;B12 concentration &lt;100 ng/L may indicate a probable B12 deficiency and the need for vitamin supplementation. A&nbsp;possible or unlikely deficiency may be associated with marker results, respectively, below and above 300 ng/L.&nbsp;Finally, in subjects with B12 concentrations &gt;400 ng/L, the vitamin deficiency may be excluded. Hemodialysis patients&nbsp;and pregnant woman have emerged as a target for B12 testing, although cost-effectiveness evaluations are difficult&nbsp;to perform in absence of reliable literature data. Monitoring B12 concentrations in serum to evaluate the effectiveness&nbsp;of B12 supplementation is not clinically useful.</p>
Biochimica Clinica ; 38(4) 326-329
Documenti - Documents
Cancer biomarkers 2013: appunti a margine del convegno satellite EuroMedLab
Cancer biomarkers 2013: notes about the EuroMedLab satellite meeting
<p>Like all other interventions and devices&nbsp;in health care, cancer biomarkers should undergo a careful validation process before they are introduced into clinical&nbsp;practice for diagnostic or prognostic purposes. Particularly, for those candidate diagnostic markers, validation implies&nbsp;the assessment of their diagnostic accuracy according to pre-specified and standardized criteria. For prognostic&nbsp;purposes, large, protocol-driven prospective studies should assure unbiased results on the effectiveness of the&nbsp;investigated biomarkers in predicting patient&rsquo;s risk of a future outcome, in aiding individual treatment choice and in&nbsp;patient counselling. The improvement of the methodology of research should finally contribute evidence of high level&nbsp;and strength useful to recommend or not the appropriate application of specific biomarkers in different clinical settings&nbsp;(screening, primary/secondary care, treatment monitoring, follow-up). In this presentation, we summarized the major&nbsp;issues highlighted during the recent EuroMedLab satellite meeting held in Venice (IT) on May 2013, in which&nbsp;standardized processes from the evaluation of biomarkers&rsquo; diagnostic accuracy and prognostic value for guideline&nbsp;development were discussed. In addition, current efforts on the research of novel molecules and therapeutic targets&nbsp;(proteins, exosomes, circulating nucleic acids) candidate to clinical introduction were briefly reviewed.</p>
Biochimica Clinica ; 37(6) 479-492
Opinioni - Opinions
Il laboratorio nel cancro dell’ovaio: e pur si muove!
Laboratory and ovarian cancer: and yet it moves!
Biochimica Clinica ; 37(3) 176-178
Editoriale - Editorial
Serum human epididymis protein 4 vs. carbohydrate antigen 125 for ovarian cancer diagnosis: a systematic review
<p>Human epididymis protein 4 (HE4) measurements in serum have been proposed for improving the specificity of&nbsp;laboratory identification of ovarian cancer (OC). This study sought to critically revise the available literature on the&nbsp;comparison between the diagnostic accuracy of HE4 and carbohydrate antigen 125 (CA-125) to provide evidence of&nbsp;HE4 additional clinical value. Literature search was undertaken on electronic databases and references from&nbsp;retrieved articles, and articles analyzed according to predefined criteria. Meta-analyses for HE4 and CA-125&nbsp;biomarkers with odds ratio (OR), diagnostic sensitivity, specificity, positive (LR+) and negative (LR&ndash;) likelihood ratios&nbsp;as effect sizes were performed. Sixteen articles were originally included in meta-analyses, but two for HE4 and one&nbsp;for CA-125 were eliminated as outliers. Furthermore, for HE4 a publication bias was detected. ORs for both HE4&nbsp;(37.2, 95% CI: 19.0-72.7, adjusted for publication bias) and CA-125 (15.4, 95% CI: 10.4-22.8) were significant,&nbsp;although in a heterogeneous set of studies (P &lt;0.0001). By combining sensitivity and specificity, the overall LR+ and&nbsp;LR&ndash; were 13.0 (95% CI: 8.2-20.7) and 0.23 (95% CI: 0.19-0.28) for HE4 and 4.2 (95% CI: 3.1-5.6) and 0.27 (95% CI:&nbsp;0.23-0.31) for CA-125, respectively. HE4 measurement seems to be superior to CA-125 in terms of diagnostic&nbsp;performance for identification of OC in women with suspected gynecological disease. Due to the high prevalence of&nbsp;OC in post-menopausal women and the need of data focused on early tumor stages, more studies tailored on these&nbsp;specific subsets are needed.</p>
Biochimica Clinica ; 37(3) 179-189
Rassegne - Reviews
Un raro caso di mesotelioma multicistico del peritoneo associato ad aumento di CA 125 e CA 19.9 nel siero
A rare case of benign multicystic mesothelioma of the peritoneum associated to CA 125 and CA 19.9 elevations in serum
S. Ferraro  |  R. Mozzi  |  C. Villa  |  M. Crespi  |  M. Panteghini  | 
<p>Markedly increased CA 125 and CA 19.9 concentrations in serum are considered specific&nbsp;enough to reliably identify malignant cancers (ovarian and gastrointestinal tumours, respectively), although a&nbsp;consistent body of literature has reported marker elevations in several benign conditions. Here we report the case of&nbsp;a woman in post-menopausal status, with a previous history of hysterectomy, presenting with a 12-cm pelvic mass at&nbsp;sonography and serum CA 125 and CA 19.9 concentrations &gt;400 kU/L. One month after initial presentation, she&nbsp;underwent surgical evaluation for laparoscopy, repeating marker determinations. Concentrations of CA 125 and CA&nbsp;19.9 were still elevated, but decreased if compared with the previous data (~200 kU/L). Magnetic resonance imaging&nbsp;characterized a multicystic mass in the mesentery, allowing to hypothesize a benign multicystic mesothelioma of the&nbsp;peritoneum (BMMP). The laparoscopy revealed multiple cysts, some of them resulting in colliquation, associated to&nbsp;ascites. Histological examination of biopsy specimens confirmed BMMP as composed of multiple, thin-walled,&nbsp;irregularly spaced cysts lined by flattened and cuboidal mesothelial cells. The cystic colliquation was though as the&nbsp;main cause for decrease in marker concentrations. To our knowledge, this is the first case of BMMP associated with&nbsp;significantly increased concentrations of CA 125 and CA 19.9 and their decrease before any surgical treatment.</p>
Biochimica Clinica ; 37(3) 241-245
Casi Clinici - Case Report
Un ulteriore passo verso una migliore efficienza ed efficacia della determinazione della calprotectina fecale
A further step to improve the cost-effectiveness of calprotectin determination
Biochimica Clinica ; 37(2) 133-134
Lettere all'Editore - Letters to the Editor
Frequenza e significato clinico di valori di antigene carboidratico (CA) 19.9 marcatamente elevati in una popolazione di pazienti ospedalizzati
Prevalence and clinical significance of enormously increased carbohydrate antigen (CA) 19.9 concentrations in hospitalised patients
<p style="text-align: justify;">Markedly elevated CA 19.9 concentrations in serum are regarded as specific enough to reliably identify pancreatic cancer, even if a consistent body of literature shows CA 19.9 concentrations &gt;1000 kU/L in a variety of benign conditions. Scarce data are, however, available on the prevalence and clinical significance of CA 19.9 values &gt;10,000 kU/L. Here we present a case series of 18 consecutive patients admitted to our hospital in a time period of 14 months showing an enormous elevation of CA19.9 concentrations (11,568 to &gt;100,000 kU/L), with the aim to assess the association of such concentrations with the presence of pancreatic cancer and, more in general, with tumours of the gastrointestinal system. We also tried to define whether the exact measurement of CA 19.9 concentrations in this range, which needs serial sample dilutions, is cost-effective. CA 19.9 measurements, including sample dilutions according to a defined laboratory protocol, were performed on Roche Modular EVO system. The yearly prevalence of hospitalized patients tested for CA 19.9 and with marker concentrations &gt;10,000 kU/L was 2.9%. All recruited patients were diagnosed as malignancies: 15 had primary or secondary pancreatic cancer, two had gastric cancer, and one a cholangiocarcinoma. CA 19.9 concentrations ranged between &gt;10,000-30,000 kU/L in 9 cases, &gt;30,000-60,000 kU/L in two, &gt;60,000-100,000 kU/L in three, and &gt;100,000 kU/L in four cases, respectively. A surgical resection of the tumour was performed in five patients, independently of CA 19.9 concentrations. The median patient&#8217;s survival was &lt;6 months. In conclusion, CA 19.9 concentrations &gt;10,000 kU/L unequivocally identify a gastrointestinal malignancy, more frequently (&#126;83%) a primary or secondary pancreatic cancer. Exactly measuring CA 19.9 concentrations &gt;10,000 kU/L after multiple sample dilution does not add relevant information for patients&#8217; prognosis and treatment.</p>
Biochimica Clinica ; 36(6) 436-440
Casi Clinici - Case Report