PubMed Health⌕ Search

Biomedical subjects

Stefano Ciatto

Publications and source records attributed to Stefano Ciatto.

At least 19 recordsLinked to original sources

Detection rates of high-grade prostate cancer during subsequent screening visits. Results of the European Randomized Screening Study for Prostate Cancer.

Screening for prostate cancer using prostate-specific antigen (PSA) tests has led to a stage and grade shift as compared to the pre-PSA era. Effectiveness of screening for prostate cancer should be manifested by a reduction in detection rate of aggressive cancers during subsequent screening. In 6 centers of the European Randomized Screening study for Prostate Cancer, a total of 58,710 men were tested for prostate cancer. Screening centers differed with regard to age-range, screening interval and biopsy indications. During the 2nd visit, the proportion of Gleason score 6 cancers increased from 62.5 to 75%, mainly at the expense of Gleason score 7 cancers. High-grade (Gleason score 8-10) cancer detection rates varied per screening center during the 1st visit from 5.1 to 41.1, and during the 2nd visit from 6.4 to 29.3/10,000 men. The overall detection rate of high-grade cancers showed a reduction during the 2nd visit from 26 to 12/10,000 men, an effect mainly attributable to the screening center with the highest cancer detection rate (i.e. 507/10,000 men). Variations in detection rates among screening centers related among others to biopsy compliance and age range.

Age Factors↗

Role of P16(INK4a) expression in identifying CIN2 or more severe lesions among HPV-positive patients referred for colposcopy after abnormal cytology.

BACKGROUND: p16 is strongly overexpressed in dysplastic cervical cells because of the transforming activity of the E7 oncogene of all high-risk human papillomavirus (HR-HPV) types and may be easily revealed by immunochemistry: p16 may, therefore, be considered a surrogate marker for the activated oncogene expression of HR-HPV in dysplastic cervical cells. METHODS: HPV and p16(INK4a) testing were performed in a consecutive series of 283 patients with abnormal cytology referred to colposcopy assessment or follow-up. Triage of patients to colposcopy by HPV or HPV and p16 testing was simulated, and the relative sensitivity, specificity, and positive predictive value (PPV) of HPV and p16 testing for > CIN2 lesions was determined as well as the cost balance of the two triage types. RESULTS: Compared to current protocol, triage by HPV testing reduced the number of colposcopies by 44.2%, but also reduced the > CIN2 detection rate by 10.7%, and was associated with a cost of euro 54.16 per assessed woman and of euro 613.20 per > CIN2 detected. Compared with current protocol, triage by HPV and p16 testing combined reduced the number of colposcopies by 73.1%, but reduced > CIN2 detection rate by 21.5%, and was associated with a cost of euro 54.73 per woman assessed and of euro 704.09 per > CIN2 detected. CONCLUSIONS: Triage by HPV and p16 improves considerably the PPV of diagnostic assessment, but decreases > CIN2 detection rate, and is associated with substantially higher costs. Further decrease of molecular immunochemistry testing due to technological progress may allow HPV and p16 testing to become a cost effective procedure in the future.

Adult↗

Radiological surveillance of interval breast cancers in screening programmes.

Interval breast cancers-those diagnosed after a negative mammographic screen and before the next scheduled screen-are an important indicator of the potential effectiveness of population screening for breast cancer. Although the incidence of interval cancers is usually monitored, radiological surveillance is not undertaken routinely in most screening programmes. Here, we describe radiological surveillance of interval breast cancers and discuss methodological difficulties in the radiological review process and in the categorisation of interval cancers as false-negative, true, or occult. Furthermore, we identify methods that affect whether an interval cancer is classified as a false-negative (missed) or a true interval cancer. For all radiological categories of interval cancers, we outline possible changes to screening programmes that might improve cancer detection. Standardised radiological surveillance of interval cancers might allow within-programme comparisons and has the potential to guide practice and improve quality.

Breast Neoplasms↗

Analysis of morphologic patterns of fine-needle aspiration of the breast to reduce false-negative results in breast cytology.

BACKGROUND: The identification of specific morphologic diagnostic criteria is of paramount importance to optimize the accuracy of fine-needle aspiration cytology (FNAC) and to reduce the rate of false-negative results. In the current study, the authors reviewed a consecutive series of false-negative findings observed in the study center to define the presence and degree of cytologic abnormalities. False-negative cases were randomly mixed with true-negative cases and were reviewed by a panel of expert readers in a blinded fashion. The main objective of the current study was to identify a morphologic pattern that may permit the reduction of false-negative findings while maintaining the specificity of FNAC. METHODS: A blind review of a set of 41 consecutive false-negative and 49 true-negative breast aspiration samples was performed by a panel of 10 expert cytologists who were asked to give a final report and to classify the samples according to classic morphologic parameters. RESULTS: The majority final report sensitivity was 54% (range, 19-61%) and specificity was 73% (range, 65-92%). The average concordance with the majority report, adjusted for chance agreement (kappa statistic), was moderate at 0.54 (range, 0.40-0.65). Enlarged nuclear size, a hyperchromatic nucleus, the absence of naked nuclei, and the absence of apocrine metaplasia were reported more frequently in carcinoma cases, although not to a significant extent. The only variable found to be associated significantly (P = 0.041) with a diagnosis of carcinoma was the presence of microcalcifications, which nevertheless were found to occur in only a minority of carcinoma cases (7 of 41 cases) or controls (2 of 49 controls). Multivariate analysis demonstrated that the presence of microcalcifications (odds ration [OR] of 3.0; 95% confidence interval [95% CI], 1.2-7.4), the absence of naked nuclei (OR of 2.4; 95% CI, 1.3-4.4), and enlargement of the nucleus (OR of 1.9; 95% CI, 1.1-3.4) were all independently associated with false-negative findings. Diagnostic accuracy using a morphology-based score did not appear to improve the results substantially compared with the final report (sensitivity of 0.46 vs. 0.54 [P = 0.508] and a specificity of 0.80 vs. 0.73 [P = 0.218]). CONCLUSIONS: The results of the current study confirm that breast FNAC false-negative results are at least partially the result of underreporting of abnormalities that may be noted at review. Detailed analysis of a single morphologic characteristic was found to be of limited diagnostic value, suggesting that operators do perceive abnormalities but cannot translate these findings into distinct morphologic categories.

Biopsy, Fine-Needle↗

Triage with human papillomavirus testing of women with cytologic abnormalities prompting referral for colposcopy assessment.

BACKGROUND: The current study was conducted to evaluate the cost-effectiveness of triaging for colposcopy using human papillomavirus (HPV) testing. METHODS: HPV tests were performed in a consecutive series of women who were referred for colposcopy for persistent atypical squamous cells of undetermined significance (ASCUS)-favor reactive (n = 35 women), ASCUS-favor squamous epithelial lesion (n = 164 women), atypical glandular cells of undetermined significance (n = 74 women), low-grade squamous epithelial lesion (n = 161 women), or high-grade squamous epithelial lesion (n = 78 women). The cost effectiveness of triaging women with ASCUS results using HPV testing was determined compared with the current protocol. RESULTS: The sensitivity of HPV testing for cervical intraepithelial neoplasia > Grade 2 was very high. Cost analysis showed a moderate increase in cost with the addition of HPV triage. CONCLUSIONS: Because HPV testing is highly sensitive, it may be useful as an alternative to the current policy of 6-month repeat cytology for women with ASCUS.

Cervix Uteri↗

Determining overdiagnosis by screening with DRE/TRUS or PSA (Florence pilot studies, 1991-1994).

The rate of overdiagnosis of prostate carcinoma was assessed by following 6890 participants in pilot screening studies from 1991 to 1994. Observed/expected incidence and mortality were determined using data from the Cancer and Mortality Registry. The cancer detection rate (1.75%) and observed/expected ratio (12.5:1) were high at the first screening, and substantially lower at the second screening (0.65% or 4.10:1). According to the registry follow-up, prostate cancer occurred in 225 subjects in the whole study cohort, while 178.2 were expected with 50652 men/years at risk. The standardised incidence rate was 1.66 in the screened (95%CI=1.4-2.0), 0.97 in the non-responders (95%CI=0.8-1.2) and 1.23 in subjects excluded from invitation due to previous cancer or major illness (95%CI=0.8-1.5). A 66% excess incidence rate was observed in the screened subjects over a 9-year period, confirming previous estimates of overdiagnosis.

Aged↗

Accuracy of prostate volume measurements using transrectal multiplanar three-dimensional sonography.

The aim of this study is to evaluate the accuracy of three-dimensional (3D) ultrasound in comparison with conventional bidimensional (2D) sonography in prostatic calculations. The study was performed using a Kretztechnik Voluson 530D machine with a 7.5 MHz endocavitary transducer. From March 1998 to March 2000, we examined 80 patients (63-74 years, mean 68 years). There were 59 patients with benign prostate hypertrophy (BPH) and 21 with prostate cancer awaiting a radical prostatectomy. The mean absolute error in 3D ultrasound measurement was +/-0.2-3 mL. (range of error was 6.5%). Volume measurement using 2D ultrasound methods was much less accurate than 3D ultrasound methods: +/-0.4-5 mL. (range of error was 35%). Both 2D and 3D measurements show that the margin of error depends on the frequent presence of a third prostatic lobe, on the morphology, and on the size of the prostatic gland. The precise estimation of prostate volumes may provide information on the real effectiveness of some therapies that act on the reduction in volume of benign alteration, such as in prostatic hypertrophy, and may eliminate the current limits of 2D sonography with a significant clinical contribution for virtually no extra cost.

Aged↗

Quality assessment of the mammographic screening programme in the Azienda Sanitaria locale Provincia Milano 1 -- analysis of interval cancers and discussion of possible causes of diagnostic error.

PURPOSE: To evaluate the sensitivity of the mammographic screening programme and the causes of diagnostic fault in cases surfacing as interval cancers. MATERIALS AND METHODS: Interval cancers (CI) were identified by linkage of the screening database for the years 2000-2002 to the database of hospital discharge records (HDR) for breast cancer during 2000-2002. Linkage between screening attenders during 2000-2001 and HDR (biennial follow-up for year 2000, one year follow-up for year 2001) was used to calculate the proportional rate of observed/expected IC. The observed/ expected rate was compared with international standards and literature data. Screening mammograms followed by IC, randomly admixtured with negative controls, underwent blind review by an independent radiologist, using the recommended classification criteria to evaluate causes of error (occult, minimal signs, screening error). RESULTS: The analysis of HDR during 2000-2002 allowed us to identify 31 out of 89 expected IC. Proportional observed/expected IC rate in the first or second year of screening interval was 26 or 67%, respectively. Screening mammograms for radiological review were available in 38 of 61 total IC: 20 cases (52.6%) were classified as occult, whereas minimal signs or screening errors were 2 (5.2%) or 16 (42.1%), respectively. Diagnostic suspicion had been reported at screening in 7 of 16 cases classified as screening error, but were not diagnosed at the subsequent diagnostic assessment. CONCLUSIONS: Proportional IC rate was higher than reported in the literature or currently recommended (<30% in the 1st, <50% in the 2nd year). The analysis of error causes shows an excess of screening errors with respect to current recommendations (<20% of IC should be classified as screening error at review), but also an excess of IC suspected at screening but misdiagnosed at assessment (7/38=18.4 %). Overall the analysis revealed a reduced sensitivity of the screening programme, as often observed in service screening as compared to excellence centres, and suggests proper action to improve diagnostic accuracy. Analysis and critical review of IC is an early indicator of screening efficacy which is not currently used in Italian screening programmes. Using HDR for this purpose may have limited drawbacks, but gives the advantage of earlier identification of IC as compared to cancer registries and is the most reliable source of information in areas lacking a cancer registry. The present study methodology might be currently applied in screening programmes.

Aged↗

Role of multimedial diagnosis of breast cancer in women below 36 year of age.

PURPOSE: To evaluate the sensitivity for breast cancer of different diagnostic tests performed in a consecutive series of women aged under 36 years. MATERIALS AND METHODS: The study analyses 155 women with breast cancer incident in the Tuscany Cancer Registry from 1985 to 2000. The sensitivity of each method was evaluated in relation to the most recent test performed during the year before diagnosis and to different variables, such as tumour size and calendar period. RESULTS: Sensitivity was 70.3 % for physical examination, 76.0% for mammography, 69.1% for ultrasonography and 80.6% for cytology (86.2% if inadequate samples are excluded). Sensitivity was associated to pT category for physical examination (pT1=60.6%; pT2-4=86.4%; chi squared=10.2, p= 0.001) and for ultrasonography (pT1=61.9%; pT2-4=92.0%; chi squared=5.7, p=0.01) and to breast radiological density for mammography (50-100% density=75.5%; 0-50% density=91.3%; chi squared=1.85, p<0.17). Among 112 cases examined with palpation, mammography and cytology, these methods had a sensitivity of 78.5%, 75.8% and 91.9%, respectively, and an overall sensitivity of 98.2%. Among 65 cases examined with palpation, ultrasonography and cytology, these methods had a sensitivity of 67.6%, 70.7% and 92.3%, respectively, and an overall sensitivity of 95.3%. Among 123 cases examined with palpation, imaging (mammography and/or ultrasonography) and cytology, these methods had a sensitivity of 76.4%, 78.0% and 90.2%, respectively, and an overall sensitivity of 96.7%. Cancer was suspected by one method only in 2.4% of cases with palpation, 1.6% with imaging and 7.3% with cytology. Comparison between mammography and ultrasonography was possible in 58 cases undergoing both tests: sensitivity was 79.3% for ultrasonography and 74.1% for mammography, respectively chi squared=0.1, p=0.66). If sensitivity had been determined according to the test performed immediately before diagnosis it would have been higher, that is 74.4% for palpation, 76.8% for mammography, 73.5% for ultrasonography and 90.9% for cytology (97.7% if inadequate samples were excluded), and overall sensitivity would be 96.1%. CONCLUSIONS: Differential diagnosis of breast cancer in women aged under 36 years is difficult, sensitivity being lower as compared to older women, with the only exception of cytology. The association of multiple tests (diagnostic imaging and cytology) is crucial to achieve an acceptable false negative rate. In particular, the extensive use of cytology in the presence of an even minimal doubt at palpation and/or imaging is strongly recommendable. Sensitivity must be calculated on the basis of an independent pathology registry, and false negatives must be defined within a given period after the test. Analysis limited to tests performed immediately before diagnosis leads to a biased overestimation of sensitivity.

Adult↗

Conventional versus digital mammography in the analysis of screen-detected lesions with low positive predictive value.

PURPOSE: To compare the performance of screen-film and digital mammography in the assessment of screen-detected breast lesions. MATERIALS AND METHODS: A series of 100 consecutive mammographic screen-detected lesions (65 masses, 6 architectural distortions, 29 microcalcifications) deserving diagnostic assessment and judged to have a low positive predictive value underwent screen-film mammography (SFM) and digital mammography by a Fuji computed radiography system (FCR) (double exposure, same view, without removing compression) of the corresponding breast. Three sets of images (SFM, hard copy and soft copy FCR) were read, blind of assessment outcome, by three experienced radiologists. For the three different imaging modalities a contrast-detail analysis, dose evaluation and diagnostic accuracy by means of ROC analysis were performed. At the end of the diagnostic workup all suspicious cases (20) underwent surgical biopsy and were histologically confirmed as cancers and the cases which were negative or benign at assessment (80) were followed up for a period of 12-20 months. During the follow-up period two more cases proved to be cancers at subsequent examinations. RESULTS: Contrast-detail analysis gives better image quality for FCR compared to SFM at the same delivered dose, whilst in ROC analysis the SFM (AUC 0.7158), hard copy FCR (AUC 0.7404) and soft copy FCR (AUC 0.7501) (chi(2)=1.30, p=0.5220) are equivalent. CONCLUSION: FCR has a diagnostic performance equivalent to SFM in the assessment of screen-detected lesions with a low positive predictive value for cancer and it may be safely included in routine screening practice.

Breast Neoplasms↗

Increasing trends of cervical adenocarcinoma incidence in Central Italy despite Extensive Screening Programme, 1985-2000.

Incidence rates of adenocarcinoma of the uterine cervix have been reported to be increasing in several countries, but not in Italy. The aim of the present study was to analyse trends in cervical cancer incidence by histological type in two districts of Central Italy (Florence and Prato), covered by the Tuscany Cancer Registry (RTT), where cytological screening had been available since the 1970s. Incident cervical cancers during 1985-2000 were 1012. Estimated Annual Percent Change (EAPC) by age-groups and histological type were computed. Incidence increased for adenocarcinoma (EAPC = +5.7%; 95% confidence interval (CI)+2.8; +8.6); whereas, it decreased for squamous cancer (EAPC = -1.9%; 95% CI-3.8; 0) and for other or not specified types (EAPC = -4.4%; 95% CI-10.0; +1.5). Adenocarcinoma increased significantly among younger women (<55 years) but not among older ones, whereas squamous cell cancer decreased among older women only. The burden of cervical cancers might increase in the future if no specific preventive strategies for adenocarcinoma are implemented.

Adenocarcinoma↗

Prognostic impact of the early detection of metachronous contralateral breast cancer.

The study aimed to assess whether the early detection of asymptomatic metachronous contralateral breast cancer (MCBC) improves the prognosis of the patient compared with a diagnosis at symptomatic onset. We reviewed 339 MCBC cases that were consecutively diagnosed from 1970 to 2001, for which reliable information on subjective symptoms was available. The association of early (asymptomatic vs. symptomatic) detection with mortality from breast cancer was studied by univariate and multivariate analyses, adjusting for potential confounders. A more favourable stage at diagnosis was evident for asymptomatic vs. symptomatic MCBC (pT1=84.2% vs. 58.1%, pN0 65.0% vs. 52.4%). The hazard ratio (HR) of breast cancer death was approximately half (0.49%, 95% Confidence Interval (CI) 0.29-0.83, P = 0.008) for asymptomatic vs. symptomatic MCBC. Although length bias may have occurred (symptomatic MCBC had a shorter free interval from the first cancer), the present evidence supports the practice of active follow-up aimed at the early detection of asymptomatic MCBC.

Adult↗

Role of ultrasound-guided fine needle cytology of axillary lymph nodes in breast carcinoma staging.

PURPOSE: To evaluate the efficacy of cytology on axillary lymph node ultrasound-guided aspiration biopsy in the reduction of inappropriate surgery, such as the sentinel node (SN) procedure if positive, or axillary dissection if negative. MATERIALS AND METHODS: Cytology was performed on 159 consecutive cases, on the ultrasonographically most suspicious lymph node. Lymph node histology was used as a reference standard to determine accuracy. Four different scenarios were simulated: routine axillary ultrasonography with cytology of the lymph nodes visible at ultrasonography (A), or of only the lymph nodes suspicious at ultrasonography (B), with ultrasonography limited to clinically negative axillae and cytology of the lymph nodes visible at ultrasonography (C), or only of the lymph nodes suspicious at ultrasonography only (D). RESULTS: Cytologic sensitivity was 58.6%, specificity 100%. Immediate axillary dissection only in the case of positive cytology would have avoided 6/6 inappropriate axillary dissections and 5/34 (14.7%) inappropriate SN, compared to routine practice (immediate dissection for palpable adenopathy, SN in the remaining cases). Each of the simulated scenarios saved inappropriate surgical procedures (A: 6 dissections, 5 SNs; B: 6 dissections, 3 SNs; C: 13 SNs; D: 11 SNs) at no expense (A and B) or limited expense (C: Euro 348, D: Euro 232 for each inappropriate surgical procedure saved). CONCLUSIONS: Axillary lymph node cytology can save axillary dissections or sentinel node procedures and is recommended as routine practice. Routine axillary ultrasonography, with cytology of sonographically visible lymph nodes, followed by immediate axillary dissection only in case of positive cytology proved to be the best approach in terms of cost-benefit ratio.

Adult↗

A feasibility study of the use of the AutoPap screening system as a primary screening and location-guided rescreening device.

BACKGROUND: The AutoPap 300 QC system (Tripath Imaging, Inc., Burlington, NC) is an automated device that was designed to screen conventionally prepared cervical smears and, more recently, thin-layer slide preparations. The system has been tested in large clinical trials. METHODS: A total of 14,145 cervical smears obtained from participants in the Florence screening program were eligible for the study. Smears were processed first with the AutoPap system and were classified into three different categories: 1) no further review (NFR), 2) review, and 3) process review (PR). Conventional manual reading was performed by 10 experienced cytopathologists. RESULTS: After AutoPap processing, 2398 smears were classified as NFR (16.9%), and 1818 smears were classified as PR (12.8%). Overall, there were 188 inadequate smears (1.3%) at conventional review and 125 inadequate smears (0.88%) at AutoPap review. Six-month repeat smears were prompted by 330 conventional reviews (2.3%) and by 222 AutoPap reviews (1.56%). Similarly, referral to colposcopy was prompted by 179 conventional reviews (1.2%) and by 147 AutoPap reviews (1.0%). Overall, 32 patients were diagnosed with high-grade cervical intraepithelial neoplasia as a result of assessment. Conventional reading detected 31 patients (28 patients were referred for colposcopy, and 3 patients were referred for repeat cytology), and the AutoPap system detected 30 patients (27 patients were referred for colposcopy, and 3 patients were referred for repeat cytology). CONCLUSIONS: The current experience suggested that conventional reading and AutoPap reading of cervical smears had essentially the same sensitivity, with slightly greater specificity for the AutoPap system. Thus, comparisons of the AutoPap system and conventional reading should focus mainly on cost analysis.

Automation↗

Comparison of standard reading and computer aided detection (CAD) on a national proficiency test of screening mammography.

OBJECTIVE: To evaluate the role of computer aided detection (CAD) in improving the interpretation of screening mammograms MATERIAL AND METHODS: Ten radiologists underwent a proficiency test of screening mammography first by conventional reading and then with the help of CAD. Radiologists were blinded to test results for the whole study duration. Results of conventional and CAD reading were compared in terms of sensitivity and recall rate. Double reading was simulated combining conventional readings of four expert radiologists and compared with CAD reading. RESULTS: Considering all ten readings, cancer was identified in 146 or 153 of 170 cases (85.8 vs. 90.0%; chi(2)=0.99, df=1, P=0.31) and recalls were 106 or 152 of 1330 cases (7.9 vs. 11.4%; chi(2)=8.69, df=1, P=0.003) at conventional or CAD reading, respectively. CAD reading was essentially the same (sensitivity 97.0 vs. 96.0%; chi(2)=7.1, df=1, P=0.93; recall rate 10.7 vs. 10.6%; chi(2)=1.5, df=1, P=0.96) as compared with simulated conventional double reading. CONCLUSION: CAD reading seems to improve the sensitivity of conventional reading while reducing specificity, both effects being of limited size. CAD reading had almost the same performance of simulated conventional double reading, suggesting a possible use of CAD which needs to be confirmed by further studies inclusive of cost-effective analysis.

Breast Neoplasms↗