Rita Passerini

Comparison of the Digene HC2 Assay and the Roche AMPLICOR Human Papillomavirus (HPV) Test for Detection of High-Risk HPV Genotypes in Cervical Samples

ABSTRACT Many different methods with different sensitivity and specificity have been proposed to detect the presence of high-risk human papillomavirus (HR HPV) in cervical samples. The HC2 is one of the most widely used. Recently, a new standardized PCR-based method, the AMPLICOR HPV test, has been introduced. Both assays recognize the same 13 HR HPV genotypes. The performances of these two commercially available assays were compared in 167 consecutive women (for a total of 168 samples) who presented at the Colposcopy Clinic either for a follow-up or for a diagnostic visit. Concordant results were found in 140/168 cervical samples (overall agreement, 83%; Cohens kappa = 0.63). Twenty-eight samples gave discordant results: 20 were positive with the AMPLICOR HPV test and negative with the HC2 assay, and 8 were negative with the AMPLICOR HPV test and positive with the HC2 assay. The genotyping showed that no HR HPV was detected in the 8 HC2 assay-positive AMPLICOR HPV test-negative samples, while in 8/20 AMPLICOR HPV test-positive HC2 assay-negative samples, an HR HPV genotype was found. The AMPLICOR HPV test scored positive in a significantly higher percentage of subjects with normal Pap smears. All 7 cervical intraepithelial neoplasia grade 3 patients scored positive with the AMPLICOR HPV test, while 2 of them scored negative with HC2. Both tests had positive results in the only patient with squamous cell carcinoma. In conclusion, this study shows that the HC2 assay and the AMPLICOR HPV test give comparable results, with both being suitable for routine use. The differences noted in some cases may suggest a different optimal clinical use.

Minor Increases in Plasma Troponin I Predict Decreased Left Ventricular Ejection Fraction after High-Dose Chemotherapy

BACKGROUND Increased cardiac troponin I (cTnI) in patients treated with high-dose chemotherapy (HDCT) for aggressive malignancy has been proposed as an early marker of late HDCT-induced cardiac dysfunction. We investigated whether cTnI measured by the Stratus CS (Dade Behring) would allow detection of minimal cTnI increases in patients treated with HDCT. METHODS Plasma cTnI concentrations were determined in 179 consecutive patients before HDCT, at the end of the treatment, and after 12, 24, 36, and 72 h. Cardiac function was explored by echocardiography, and left ventricular ejection fraction (LVEF) was recorded during follow-up. The greatest variation in LVEF from the baseline value was used as a measure of cardiac damage. RESULTS In 99 healthy volunteers, the 99th percentile was at 0.07 microg/L. On the basis of ROC curve analysis (area under the curve, 0.89), a cutoff of 0.08 microg/L was chosen (sensitivity, 82%; specificity, 77%). cTnI > or =0.08 microg/L occurred in 57 patients (32%) with echocardiographic monitoring revealing a mean decrease in LVEF of 18%. In comparison, the group of cTnI-negative patients had a mean decrease in LVEF of 2.5% (P <0.001). CONCLUSIONS Plasma cTnI, as measured with the Stratus CS, can detect minor myocardial injury in patients treated with HDCT.

Comparison of HE4, CA125 and ROMA algorithm in women with a pelvic mass: correlation with pathological outcome.

OBJECTIVE The quality of first surgery is one of the most important prognostic factors in ovarian cancer patients. Pre-surgical distinction of benign and malignant pelvic mass plays a critical role in ovarian cancer management and survival. The aim of this study was to evaluate the clinical performance of ROMA algorithm and of CA125 and HE4 in the triage of patients with a pelvic mass undergoing surgery, in order to discriminate benign from malignant disease. METHODS Three hundred and forty-nine pre- and post-menopausal women, aged 18 years or older undergoing surgery because of a pelvic mass were enrolled: serum concentrations of CA125 and HE4 were determined and ROMA was calculated for each sample. RESULTS Median serum CA125 and HE4 levels were higher in patients with EOC compared to subjects with benign disease (p<0.0001). The resultant accuracy (using Receiver Operating Characteristics, ROC Area) values for HE4, CA125 and ROMA showed a good performance ranging from 89.8% for CA125 in pre-menopausal patients to 93.3% for ROMA in post-menopausal patients: AUC for ROMA resulted significantly higher in comparison to CA125 alone (93.3% vs 90.3%, p=0.0018) in post menopausal patients. A sub-analysis considering the 40 patients with endometrioid disease showed the highest accuracy of HE4 in these patients. CONCLUSIONS Data presented confirm the accuracy of HE4 and of the ROMA algorithm in the distinction of ovarian carcinoma from benign disease, with a trend towards better performance for ROMA than for CA125 alone, statistically significant in postmenopausal patients.

Typing of human papillomavirus in women with cervical lesions: Prevalence and distribution of different genotypes

Human papillomavirus (HPV) are distributed widely and persistent infection with high‐risk (HR) HPV is recognized as a necessary cause of cervical cancer. The aim of this study was to evaluate the distribution of different HR‐HPV genotypes in 199 women with cervical pre‐invasive lesions undergoing conservative treatment. A Linear Array HPV Genotyping Test was used to identify individual HPV genotypes in cervical samples. It was observed that the most prevalent HPV genotypes were HPV 16 (52.6%), HPV 51 (13.5%), and HPV 31 (10.9%); HPV 18 was found in 7.3% of the patients. Stratifying the different HPV genotypes according to the severity of the cervical lesion, a strong association between the increasing severity of the histological diagnosis and the detection of more carcinogenic HR‐HPV type was found, and in all but one cervical intraepithelial neoplasia of grade 3 the presence of at least one HR‐HPV could be detected, with more than 70% of cervical intraepithelial neoplasia of grade 3 patients bearing HPV 16. Multiple infections, comprising between 2 and 6 HPV types, were found in 43% of patients; however, the presence of more than 1 HR‐HPV type was not associated with an increased risk of high grade lesions. In conclusion, this data show that HPV 16, 51, 31, 52, and 18 were the prevalent types found in patients with cervical lesion undergoing conservative treatment, with a high prevalence of HPV 16 in cervical intraepithelial neoplasia of grade 3 patients. No association between multiple infection and severity of the lesion could be found. J. Med. Virol. 81:271–277, 2009.

Serum EGFR and Serum HER-2/neu Are Useful Predictive and Prognostic Markers in Metastatic Breast Cancer Patients Treated With Metronomic Chemotherapy

Metronomic chemotherapy has been demonstrated to be of value in patients with advanced breast cancer. No reliable markers of response are available. In breast tumor, HER‐2/neu is a prognostic factor, whereas no definite data exist for EGFR. The aim of the study was to evaluate the prognostic and predictive role of serum HER‐2/neu and serum EGFR in breast cancer patients treated with low‐dose chemotherapy.

The Pitfalls of CA19-9 Routine Testing and Comparison of Two Automated Immunoassays in a Reference Oncology Center

We evaluated CA19-9 as a marker of various malignancies and compared the results of 2 commercial immunoassays. The Abbott ARCHITECT i2000 and Roche cobas 410 immunoassays were used on 500 consecutive samples to evaluate the frequency of positive results by cancer type and the correlation between assays. The patients were tested before or after surgery and/or during chemotherapy. The rate of results exceeding conventional thresholds was 92.3% in pancreatic cancer, 36.8% in gastric cancer, and ranged from 3.0% to 35.9% in other tumors. Agreement (90.6%) and correlation (R(2) = 0.865) between the 2 assays were good and the frequency of highly discordant results was low (6/500). In some cases, interference by heterophilic antibodies was demonstrated. The 2 methods were comparable in diagnostic accuracy and had good correlation but are not interchangeable. Patients should always be monitored for CA19-9 with the same method and it should be indicated in the report.

Interchangeability of measurements of CA 19-9 in serum with four frequently used assays : an update

Abstract Background: CA 19-9 is a marker principally related to pancreatic and gall bladder cancer. Although its determination has no value in screening for these malignancies, it is used in post-operative monitoring and during chemotherapeutic treatment of confirmed disease. Measurements during follow-up must be comparable and must be performed with standard, validated methods. Methods: We compared four routinely used analytical systems for CA 19-9 determination: the Architect i2000 and AxSYM systems from Abbott Laboratories, the Elecsys 1010 from Roche Diagnostics, and the KRYPTOR system from Brahms Diagnostics. We evaluated the analytical performance of the four systems and compared measurements of CA 19-9 values, which covered the whole analytical range. Results: The analytical performance and accuracy of the four systems were fairly good, but Passing-Bablok regression and mountain plots showed significant differences in CA 19-9 values measured with the four platforms. Conclusions: Our data indicate that during tumor follow-up, the use of the same system is appropriate to avoid the risk of a variation due to the method rather than the disease. Moreover, whenever a change in analytical equipment is required, careful analysis of CA 19-9 results must be undertaken. Clin Chem Lab Med 2007;45:100–4.

Interference of antibiotic therapy on blood cultures time-to-positivity: analysis of a 5-year experience in an oncological hospital.

This study performed a retrospective analysis on the relationship between blood culture time-to-positivity (TP) and type of isolated microorganism, antibiotic administration, and immunological status of the patients. We analyzed the data related to 1,218 positive blood cultures. When compared to Gram positive bacteraemia, the percentage of Gram negative growth was higher and the mean TP significantly shorter (p < 0.0001). In patients receiving antibiotics, median and mean TPs of blood culture were different for Gram positive bacteraemia (log-rank p = 0.0022, Wilcoxon p < 0.0001) but not for Gram negative (log-rank p = 0.4011, Wilcoxon p = 0.1585). No statistically significant effect on TP was found for sampling site, interaction between sampling site and antibiotic administration, and immunological status of the patient. In conclusion, TP is independent of antibiotic therapy in cases of Gram negative bacteraemia, while for Gram positive bacteraemia a prolongation of TP occurs.

Timing of breast cancer surgery in relation to the menstrual cycle: an update of developments

It is well-established that hormones have multiple effects on breast cancer. Some, but not all studies indicate that the phase of the menstrual cycle (and hence hormonal status) at the time of breast surgery may influence survival. In this paper we review the literature in this area, explore how it is possible that such an association may occur, and note that randomised studies which unambiguously determined the phase of the cycle at the time of the operation are lacking. We go on to describe an ongoing self-randomised trial designed to address this problem and present preliminary results which show that only about 75% of the women ovulated during the cycle in which the operation took place, and that the established prognostic factor Ki-67 varied with the phase of the cycle in women who ovulated. It is too early to assess the significance of this finding.

Atrial fibrillation after thoracic surgery for lung cancer: use of a single cut-off value of N-terminal pro-B type natriuretic peptide to identify patients at risk

Postoperative atrial fibrillation (AF) is a well-known complication occurring after thoracic surgery. B-type natriuretic peptide has recently been investigated as a predictive marker of postoperative AF after cardiac surgery. The aim of this study was to evaluate a definite cut-off for N-terminal pro-B type natriuretic peptide (NT-proBNP) in predicting postoperative AF in lung cancer patients. NT-proBNP was determined before and after surgery in 400 patients. Cardiac function was monitored by continuous postoperative ECG and clinical cardiological evaluation. AF occurred in 18% of the patients. Receiver operating characteristic curve analyses identified a cut-off of 182.3 ng l−1 as the one with the highest sensitivity and specificity. Perioperative increased levels of NT-proBNP seem to predict postoperative AF in patients undergoing thoracic surgery, and a single cut-off of 182.3 ng l−1 can be used to select high-risk patients who could receive preventive therapy, leading to a considerable decrease in the total costs associated with the management of this complication.