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Biomedical subjects

M Confortini

Publications and source records attributed to M Confortini.

At least 19 recordsLinked to original sources

Association of FOBT-assessed faecal Hb content with colonic lesions detected in the Florence screening programme.

We assessed the correlation between quantitative results of immunological faecal occult blood testing (I-FOBT) and colonic lesions (191 colorectal cancers, 890 adenomas) detected at colonoscopy in 2597 FOBT+ (cutoff 100 ng ml(-1) Hb) subjects. At univariate analysis, a higher average faecal Hb content was significantly associated with male gender (P=0.003), age (P=0.02), and colonoscopy findings (P=0.000). Among adenomas, higher faecal Hb content was significantly associated with size (P=0.0000), presence of severe dysplasia (P=0.0001), presence of villous component (P=0.0002), and location in the left colon (P=0.003). At multivariate analysis adjusting for potential confounders, age (P=0.03), size (P=0.0000), and location in the left colon (P=0.0005) were confirmed as having an independent association with higher faecal Hb content. Immunological FOBT is confirmed to be a specific screening test to detect cancer and adenoma, with a low positivity rate (3.7%) and a high positive predictive value (41.5%). Faecal Hb content is significantly higher for those lesions (cancer and high-risk adenomas) screening is aimed at detecting.

Aged↗

Interlaboratory reproducibility of atypical glandular cells of undetermined significance: a national survey.

OBJECTIVE: The aim of this study was to evaluate the inter-laboratory reproducibility for atypical glandular cells (AGC) (The Bethesda System (TBS) 2001) of the laboratories involved in the screening programmes in Italy. METHODS: A set of 35 selected slides were circulated among 167 laboratories involved in local population-based cervical screening programmes. Each laboratory provided one single diagnosis per smear. The smears were read blind to the original diagnosis and to the diagnoses provided by other laboratories. A 'majority' diagnosis was defined for each case and assumed as the reference standard. The diagnosis provided from each laboratory was compared with the majority diagnosis. RESULTS: According to the majority report the 35 slides in the set were classified as negative in nine cases, AGC in eight, adenocarcinoma in eight, and squamous lesion or squamous + glandular lesion in 10. The crude agreement between all pairs of laboratories was 49.43%. K-values were 0.46, 0.21, 0.34, 0.36 and 0.32 for negative, AGC/AIS (adenocarcinoma in situ of endocervix), AdenoCa, Sq/Sq + Gl and all reporting categories respectively. Concordance according to overall K was moderate to substantial in 77% of the participating laboratories. CONCLUSIONS: The present study shows that the AGC category is not easily reproducible. The data confirmed the importance, in a screening scenario, of AGC/AIS diagnoses, but also presented difficulties in differentiating between the two diagnoses. In addition to the results obtained from the circulation of the slides, laboratories which had annually a low number of cervical smears were able to gain experience focused on particular morphological pictures.

Adenocarcinoma↗

Technical evaluation of the new thin layer device CellSlide (Menarini Diagnostics).

The CellSlide Processor (Menarini Diagnostics) is an automatic computer-controlled instrument, designed to prepare standardized, thin-layer cytological preparations using a filtration process. In this report, this new processor has been tested in a multicentric investigation, designed to evaluate cell recovery, cellular morphology and possible time saved in reading the slide. The results of this study show that the CellSlide processing system is suitable for use in the preparation of liquid-based gynaecology samples. Furthermore, the high-quality smear produced by the CellSlide decreases the reading time by approximately 20-25%.

Histocytochemistry↗

Clinical impact (cost-effectiveness) of qualifying atypical squamous cells of undeterminate significance (ASCUS) in cases favoring a reactive or dysplastic process.

The cost-effectiveness of qualifying ASCUS cases into two different subcategories, favoring a reactive (ASCUS-R) or dysplastic process (ASCUS-S), was evaluated at the Centro per lo Studio e la Prevenzione Oncologica of Florence in a prospective study. The study determined the positive predictive value (PPV) for histologically confirmed cervical intraepithelial neoplasia grade 2 (CIN2) or more (CIN>) severe lesion of the two ASCUS subgroups. ASCUS-S had a PPV (10.78%) comparable to low-grade squamous intraepithelial lesions (LSIL) (11.40%). For ASCUS-R cases, the recommendation of 6-mo repeat cytology prompting colposcopy in cases of persistent ASCUS or more severe cytology was also effective, as it selected a subgroup with a relatively high PPV (10.34%). The cost-effectiveness of a protocol based on ASCUS qualification was compared with two other possible options for nonqualified ASCUS cases: immediate colposcopy and colposcopy in persistent ASCUS at 6-mo repeat cytology. The detection rate of CIN2> was substantially higher using ASCUS qualification (35.9 vs 14.8 or 17.1). The cost per ASCUS subject was euro 24.99, 27.11, or 25.14 and that per CIN2> detected was euro 697, 1,831 or 1,470 for the three options, respectively. The evidence that ASCUS detection option implies a higher detection rate of CIN2> and subsequently a lower cost per CIN2> detection must be considered with caution and deserves confirmation by other comparative studies.

Cervix Uteri↗

Effect of circulation and discussion of cervical smears on agreement between laboratories.

The study objective was assessing whether circulation of smears and discussion of those with differing interpretation can increase reproducibility between laboratories. The study included: the blind interpretation of a first set of 194 smears among seven laboratories, the discussion of smears with discrepant diagnoses during the previous phase and the blind interpretation of a second set of smears of same size and characteristics. After discussions, the overall weighted kappa increased in five laboratories (substantially in three : +50%, +27% and +20%). However, no change was observed in one laboratory and a slight decrease (-4%) in another. The latter interpreted the second set of smears at a longer time interval from discussions. Agreement improved for all diagnostic classes except low grade intraepithelial neoplasia (LSIL). Overall, the intervention increased diagnostic agreement, but its effect varied with laboratory and by diagnostic class and could be transient. Continued programmes of smear exchange and discussion appear to be advisable.

Cytodiagnosis↗

Interlaboratory reproducibility of atypical squamous cells of undetermined significance report: a national survey.

The study was aimed at assessing interlaboratory reproducibility in the reporting of cervical smears in the atypical squamous cells of undetermined significance (ASCUS) category. A set of 50 selected slides circulated among 89 laboratories, currently involved in population-based screening programmes for cervical cancer, which provided a diagnostic report according to four main reporting categories based on the 1991 Bethesda system. Interlaboratory agreement was determined according to kappa (K) statistics: overall and weighted K values were determined for each laboratory and for single reporting categories. The results showed a very low reproducibility for the ASCUS category. This finding supports the Bethesda system 1991 recommendation to limit the use of this reporting category and suggests that the clinical response to ASCUS reports should be decided locally, based on the observed positive predictive value for cervical intraepithelial neoplasia 2 or more severe lesions.

Diagnosis, Differential↗

Interlaboratory reproducibility of the immunocytochemical assessment of oestrogen and progesterone receptors and proliferative activity in fine needle aspiration of breast cancer.

The purpose of this study was to establish the interlaboratory reproducibility of immunocytochemical analysis of oestrogen (ER) and progesterone (PR) expression and Mib1 growth fraction on fine needle aspiration (FNA) smears. A set of 44 immunostained slides for ER, PR and Mib1 were randomly selected from the archives of the Center for the Study and Prevention of Cancer (CSPO) of Florence, Italy, and submitted for reading to 6 Italian laboratories. The generalized kappa statistic was used as an indicator of agreement among the six laboratories. A good correlation for ER and PR was evident. For Mib1 the results showed some discrepancies. In addition to adequate standardization of procedures, these data confirm that the reliability of the immunocytochemistry is strictly linked to accurate analysis of the results.

Antigens, Nuclear↗

Prediction of high-grade cervical intraepithelial neoplasia in cytologically normal women by human papillomavirus testing.

Human papillomavirus (HPV) testing has been suggested for primary screening of cervical cancer. Prediction of future high-grade cervical lesions is crucial for effectiveness and cost. We performed a case control study in a retrospective cohort of women with at least two cervical smears, all but the last one being negative, from the organized cervical screening programme in Florence, Italy. We searched for high-risk HPV in all previous, archival, smears from cases (new histologically confirmed cervical intraepithelial neoplasia (CIN) grade II or worse) and in one previous smear from each control (last smear cytologically normal, matched by age and interval (latency) from last smear). We applied polymerase chain reaction (PCR), and the b-globin gene was used as a DNA preservation marker. High-risk HPV was identified in 71/92 (77.17%) previous smears from 79 cases and 17/332 controls (5.12%). The odds ratio (OR) was 63.76 (95% CI 30.57-132.96). Among cases the proportion of HPV-positive smears declined slightly with increasing latency. Among cases, HPV was found in 81.24% (95% CI 69.93-88.96%) of smears with latency < 4 years and in 67.80% (95% CI 47.72-82.93%) of those taken at longer intervals, up to 6 years. These findings suggest that testing for high-risk HPV allows predicting 80% of CINII/III 3 years before the cytological diagnosis and two thirds 6 years before. They also suggest that testing women negative for high-risk HPV at longer interval and strictly following-up women who are HPV positive could be an effective strategy for cervical cancer screening.

Adult↗

Interlaboratory reproducibility in reporting inadequate cervical smears--a multicentre multinational study.

A set of 300 vaginal smears was interpreted by 13 cytologists from six European laboratories, who were requested to report inadequate and suboptimal smears. The set had been appropriately seeded to reach approximately 10% inadequate and 20% suboptimal smear frequency. According to the majority report, 230 smears were classified as adequate (76.7%), 43 as inadequate (14.3%), and 27 as suboptimal (9.0%). Agreement with the majority report ranged from 52% to 91% (average 78%). Kappa statistics for reporting inadequate smears showed a high level of agreement for five cytologists, and fair to good agreement for eight. In contrast, kappa statistics for reporting suboptimal smears showed fair to good agreement with the majority report only in five instances, whereas agreement was poor for eight cytologists. 'Inadequate smear' rates may be used to compare the quality of smears received in different laboratories, as there is a high level of agreement among cytologists as to what constitutes an inadequate smear. However, this is not true for "suboptimal smear" rates, and more precise reporting criteria must be defined and tested if an intermediate category is to be retained to report poor quality smears: more precise reporting criteria must be defined and tested if an intermediate category is to be retained to report poor quality smears.

Europe↗

Tamoxifen as primary treatment of breast cancer in elderly patients.

The authors report on a series of 120 elderly (age over 69) women with primary breast treated with tamoxifen alone. Treatment schedule was 160 mg on day 1 followed by a daily maintenance dose of 20 mg. Compliance to treatment was optimal and side effects were minimal. The best results achieved after at least six months of treatments were complete response in 12, a partial response in 46 and minor response in 10 patients, whereas stable disease or progression was observed in 43 or 9 patients, respectively. Response duration was limited and progression was increasingly observed over time. After 6, 12, 24, 36, 48 and 60 months the proportion of subjects still showing response to treatment was 43%, 57%, 56%, 46%, 32% and 31%, whereas progression rate was 7%, 12%, 25%, 39%, 55% and 60%, respectively, the difference being accounted for by patients with stable disease. As determined in a subset of 27 subjects, treatment response was strongly associated with immunocytochemically assessed tumor estrogen receptor content, progression being 100%, 43% or 6% in subjects with 0%, 30-60% or > 60% immunostained cells, respectively. These results do not support primary hormone therapy as a current alternative to surgery, which should be the standard treatment in otherwise healthy elderly patients with operable breast cancer. When surgery is specifically contraindicated, hormone treatment should be proposed as an alternative only in subjects with high tumor estrogen receptor content.

Aged↗

Analysis of the causes of false negative cytology reports on breast cancer fine needle aspirates.

Forty-six (2.9%) false negative reports were recorded among adequate fine needle aspirates from 1609 consecutive histologically proven carcinomas, observed from 1991 to 1993. False negatives were more frequent among younger women (< 40 years = 7.1; 40-49 years = 4.0; 50-59 years = 3.6; 60-69 years = 1.7; > 69 years = 1.5%), lobular invasive subtypes (5.4%), and smaller tumours (pT1a = 4.2; pT1b = 7.6; pT1c = 1.9; pT2 = 2.1; pT3-4 = 1.5%). The latter findings is probably ascribable to better differentiation and less precise sampling of small non-palpable tumours. No significant association was found between the false negative rate and the sampler's or reader's skill and experience. The former finding may be ascribed to the wide use of sonography guided aspiration, even for palpable masses, and the latter to the fact that readers were highly experienced and undergo periodic quality control of individual performance. False negatives were reclassified at reviews as true false negatives, reading errors or inadequates in 27, 11, and eight cases, respectively. The observed findings suggest that in most cases cytological faults were due to the absence of cytological atypia in cells sampled from well differentiated tumours, rather than to misinterpretation or sampling from adjacent normal tissues.

Adult↗

Prognostic value of breast cancer cytologic grading: a retrospective study of 213 cases.

The authors evaluate 213 consecutive breast cancer cases with positive fine-needle aspiration cytology. Cytologic smears were reviewed and classified according to a grading system. A correlation between cytologic grading and pathological stage (T and N category) was observed. Univariate analysis of 5-yr overall survival rate showed a significant negative association with prognosis only for G3 (90%) compared to G1 (72%) cases. Such prognostic correlation was no longer significant at multivariate (Cox) analysis adjusting for potential confounders such as T or N categories. The prognostic value of cytologic grading is limited and dependent on other classic prognostic indicators that are currently determined in breast cancer patients. Its practical value is negligible, as it does not improve the prognostic judgment.

Adult↗

A quality control system involving peer review of abnormal cervical smears.

An internal quality control system which is used in the centralized cytology laboratory of a population-based cervical cancer screening programme in Florence is described. It includes a peer review procedure. Abnormal cervical smears are circulated among all the cytologists and a consensus on the final diagnosis is reached. This daily procedure is designed to evaluate the performance of each cytologist and of the laboratory as a whole but can also be considered a valuable training opportunity. During an 18-month period 1197 smears were reviewed by 15 readers using a reporting form with six main categories of reporting (from 'negative' to 'invasive carcinoma'), plus an 'unsatisfactory' category. Overall the concordance between the 15 cytologists, assessed using the kappa statistic (range 0.46-0.71; median 0.60), was good. The level of agreement increased when a weighted kappa statistic (range 0.55-0.78; median 0.68) was used. Kappa values were also calculated for specific categories and suggested an increasing concordance with increasing severity of the lesions, the categories of 'severe dysplasia' and 'invasive carcinoma' showing the highest agreement. The poor results for the 'moderate dysplasia' confirmed the need for combining this group with the 'severe dysplasia', as proposed in the Bethesda system.

Female↗

The role of fine needle aspiration cytology in the differential diagnosis of suspected breast cancer local recurrences.

The authors report on 228 cases of suspected breast cancer local recurrences studied by fine needle aspiration cytology (FNAC). The nature (malignant = 133, benign = 95) of suspected lesions was assessed on histology (no. = 46) or according to unequivocal follow-up (no. = 182). Inadequacy rate was 0.20, 0.09 or 0.35 in total, cancer or benign cases, respectively, and was particularly high (0.50) for benign chest wall lesions. Accuracy was determined on adequate smears; dubious reports were assumed as positive. Sensitivity and specificity were 0.96 and 0.97, respectively. The routine use of FNAC is recommended since it helps in the differential diagnosis of suspicious cases and may bypass surgical biopsy of positive cases not eligible for surgical treatment.

Biopsy, Needle↗

Colposcopic survey of Papanicolaou test-negative cases with hyperkeratosis or parakeratosis.

A colposcopic survey was performed in 269 consecutive women with negative cytology showing hyperkeratosis or parakeratosis. A colposcopy-guided biopsy specimen of cervical abnormalities was taken in 88 cases, and human papillomavirus infection (HPV) was detected histologically in 25 cases. No cervical intraepithelial neoplasia (CIN) was detected. The detection rate of HPV was not significantly different from that observed in a consecutive series of 1073 Papanicolaou test-negative subjects self-referred for colposcopy. Colposcopic screening of subjects showing hyperkeratosis or parakeratosis with otherwise negative smears is not recommended because it does not allow detection of cytologically false-negative CIN.

Adult↗

Detection of false-negative Pap smears using the PAPNET system.

AIMS AND BACKGROUND: False-negative cytological diagnoses represent the critical point of a screening program for early detection of cervical cancer. Computer-assisted reading using neural network technology has been suggested as a possible approach to manage the problem. The study assessed the performance and the cost-outcome ratio of computer-assisted versus conventional manual Pap smear reading. METHODS: One thousand routine smears, seeded with 81 false-negative smears, were independently interpreted by two readers by conventional and PAPNET-assisted reading. Results of both readings were compared in terms of: a)sensitivity for false-negative smears, b)specificity, and c) cost-outcome (cost per CIN2+ lesion detected). RESULTS: PAPNET-assisted reading showed a small increase in sensitivity only for one reader. Including the cost of PAPNET, the cost per detected lesion would be $7,543 and the cost per additional detected lesion would be $25,748. CONCLUSIONS: The present study provides further evidence that PAPNET-assisted screening may allow the detection of a few extra cases of CIN2+ lesions with respect to conventional reading, though at a very high cost.

False Negative Reactions↗