Re: Gelig Thurfjell M., et al. Local breast cancer recurrence caused by mammographically guided punctures. Acta Radiol. 41 (2000), 435.
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Biomedical subjects
Publications and source records attributed to S Ciatto.
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OBJECTIVES: The optimal biopsy strategy for the detection of prostate cancer still needs to be established, since a considerable proportion of clinically significant cancers remains undiagnosed on routine sextant transrectal biopsy. To assess the efficacy of transperineal biopsy to detect prostate cancer, we compared this approach to systematic sextant transrectal biopsy in a simulation experiment. METHODS: Ultrasound-guided sextant transverse (transrectal) biopsy and subsequent sextant longitudinal (transperineal) biopsy were performed on 40 radical prostatectomy specimens of patients with (transrectal) biopsy-detected prostate cancer. Conditions were simulative and may not be completely analogous to clinical settings. Ultrasound-determined prostate volume, biopsy tumor involvement, number of cores with cancer, and tumor volume were determined. Detailed mapping of radical prostatectomy specimens provided insight into the representativeness of the biopsy techniques. RESULTS: Of 40 cancers, 33 (82.5%) were redetected by the transperineal approach; 29 (72.5%) were detected by repeated transrectal biopsies. For both approaches, the tumor volume of the undiagnosed cancers was significantly smaller (P <0.01) and the prostate volume was significantly larger (P <0.01) than in the redetected ones. Between the two approaches, no difference was found for either of the variables determined in the redetected cancers. Prostate maps clarified that transperineal undiagnosed tumors were either small (0.2 cm(3) or less) or notably located at the prostatic base. CONCLUSIONS: The biopsy procedure in which the biopsy needles enter the prostate at the apex for a longitudinal direction may efficiently sample the prostatic peripheral zone. Since the experiment was artificial in design, caution should be observed in extrapolating these results to patient settings.
Screening for prostate cancer is a relatively new procedure, still under experimental evaluation within prospective randomised trials. The design of prospective studies has been mainly based on the experience of other cancer screenings, particularly breast cancer, for which data of several controlled studies are available. Unfortunately, breast cancer is very different from prostate cancer, particularly for aspects such as early diagnosis and, thus the screening process, originally modelled on the basis of the lesson taught by breast cancer screening, needs continuous re-evaluation and adjustment, based on data which are now being produced from ongoing screening experiences. In this paper, we will consider the most controversial aspects of prostate cancer screening and compare prostate screening with breast cancer screening in order to promote a better understanding of the current problems and lessons to be learned.
Until recently cervical cancer screening in Italy has been mainly spontaneous, with only a few organised programmes. This resulted in low coverage and high frequency of tests in screened women (mostly every year). The situation is, however, rapidly changing. In 1996 nationwide organised programmes, on a regional basis, were recommended. National guidelines recommend personal invitation of women aged 25-64 years for a Pap-test every third year. At the end of 1999 34% of the Italian population 25-64 years old was included in organised programmes. Most organised programmes have fail-safe systems for women referred for colposcopy, protocols for diagnostic work-up and treatment and reference centres for such phases, according to the recommendations of national and European guidelines. However the size of laboratories is frequently smaller than recommended. Most organised programmes implement quality assurance processes for cytology interpretation, that have been intensive in some centre, but there is no nationwide standardisation. In recent years data for monitoring screening activity have been collected in a standardised way by most organised programmes, in the framework of GISCi (Italian Group for Cervical Cancer Screening) allowing internal and external comparisons. In some cases strong improvements of coverage after the introduction of an organised activity have been documented. Data, however, suggest a relevant heterogeneity of criteria for cytology interpretation, requiring actions to increase consistency. The impact of these transformations on incidence of cervical cancer will be observed in the future: preliminary results suggest a reduction in older programmes.
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.
OBJECTIVE: To compare two immunochemical faecal occult blood tests based on reversed passive haemagglutination (RPHA) or latex agglutination (Hdia) in a population based screening setting. METHOD: Hdia was interpreted according to three positivity thresholds: 100, 150, or 200 ng of haemoglobin/mg of specimen solution. A total of 5844 subjects were recruited into the study, from 17432 invited subjects aged 50-70. RESULTS: Positivity rates were 3.3% for RPHA, Hdia100 3.5%, Hdia150 2.5%, Hdia200 2.0%. Among subjects complying with the diagnostic work up, colorectal cancer (CRC) was detected in 19 subjects (17 RPHA positive, 16 Hdia100 positive, 15 Hdia150 positive, 14 Hdia200 positive) and high risk adenoma/s in 41 subjects (28 RPHA positive, 32 Hdia100 positive, 29 Hdia150 positive, 25 Hdia200 positive). The prevalence of screen positive CRC in the population was for RPHA 2.9 per thousand, Hdia100 2.7 per thousand, Hdia150 2.6 per thousand, Hdia200 2.4 per thousand. The prevalence of screen positive high risk adenomas in the population was for RPHA 4.8 per thousand, Hdia100 5.5 per thousand, Hdia150 5.0 per thousand, Hdia200 4.3 per thousand. CONCLUSION: Hdia100 was as sensitive as RPHA for cancer and high risk adenomas. As Hdia is less technically complex than RPHA, it is a valid alternative to the latter, provided that full automation of the development procedure is available. Increasing the positivity threshold of Hdia up to 150 or 200 ng of haemoglobin/mg of specimen solution is not advisable as the increase in specificity is too small to justify the corresponding decrease in the detection of screen positive cancers in the population.
PURPOSE: The aim of the present study was to provide data on interval cancer incidence after the first round of the screening program in the city of Florence, and to provide and discuss the results of the review of previous screening mammograms. MATERIAL AND METHODS: The screening program "Progetto Firenze Donna" involves all women age 50 to 69 years resident in the city of Florence. In the interval from the end of the first and the start of the second screening round 51 interval cancers were identified, of which 41 were available for radiological review. Films were reviewed by expert screening radiologists, not involved in the program and blinded to the final diagnosis, according to the review criteria recommended by the UK Guidelines for radiologists (blind and informed review). RESULTS: Sensitivity (screening errors/total) was different among blind reviewers (reader A = 7.3%, reader B = 14.6%), as well as specificity which shows an inverse pattern (reader A = 98.4%, reader B = 97.6%). Informed review classified 5 cases as "screening error" (12.2%), 11 as "minimal sign" (26.8%) and 25 as "occult" (61%). Informed review classified a higher proportion of cases as "minimal sign" (minimal abnormalities are better perceived with the knowledge of the site and the pattern of subsequent cancer). DISCUSSION AND CONCLUSIONS: Analysis of interval cancers is fundamental for the quality control of a screening program. According to this experience, informed review tends to overestimate "minimal signs" in the cancer site and should not be used (or "minimal signs" should be anyhow assumed as negative). Identification of interval cases as "minimal signs" may be influenced by individual variability. Standard criteria should be adopted to identify and review/classify interval cancers to allow comparisons between different programs.
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The role of breast scintigraphy in the evaluation of 30 women with an uncertain diagnosis following triple assessment was investigated. Scintigraphy was positive in 7 of 13 cancers and 3 of 17 benign lesions and dubious in 1 of 13 cancers and 2 of 17 benign lesions. Sensitivity ranged from 61.5% to 53.8% depending whether dubious lesions were designated as positive or negative. This study shows that breast scintigraphy is not sufficiently sensitive or specific to use in the evaluation of lesions of uncertain diagnosis following triple assessment.
OBJECTIVE: To analyse the performance of a large sample of Italian radiologists undergoing a proficiency test for screening mammography. DESIGN: Evaluation of performance indicators according to reference standards determined by a panel of experts (sensitivity (reference standard > or = 80%), recall rate (reference standard < or = 15%)). SETTING: 117 Italian radiologists of varying experience (years of practice 0.5-18, average 5.9; mammograms read 500-51,000, average 13,000), all currently reporting clinical mammography and planning to take part in screening in the near future. RESULTS: Eighty four of 117 (72%) radiologists reached the standard for sensitivity, 88 (75%) reached the standard for recall rate, and only 59 (50%) reached both standards and passed the proficiency test. The probability of passing the test was significantly correlated with mammographic practice (p = 0.015), mammograms read (p = 0.024), and mammograms read/year (p = 0.043). DISCUSSION: The performance of a large sample of Italian radiologists currently reporting clinical mammography was disappointing, indicating the need for proper training of at least 50% of the tested subjects. When implementing organised screening the health authority should set up a proper process for training and accrediting radiologists, and a proficiency test should be part of such a process.
PURPOSE: We evaluated the results obtained by 130 Italian radiologists undergoing a proficiency test of clinical mammography. MATERIAL AND METHODS: Radiologists were invited to report a series of 100 mammograms (two views), including 32 cancers and 78 non-cancers, with limited information regarding age, subjective symptoms, and findings at palpation. Sensitivity and specificity were then calculated. The test was validated by a panel of experts, and standards for test sufficiency were established on that basis (sensitivity > 80%, specificity > 85%). The tested radiologists differed by mammographic practice (average = 5.7 years, range 0.5-18), total number of mammograms read (average = 8,784, range 300-50,000) and per year (average = 1,535 range 300-5,000). RESULTS: Sensitivity (standard > 80%, average 81.1%, range 39-100%) and specificity (standard > 85%, average 84.0%, range 38-98%) standards were reached by 79 (60.8%) and 81 (62.3%) radiologists, respectively. Overall, only 37 (28.5%) radiologists passed the test (reached both standards). Mammographic practice (years of experience) (chi 2 for trend 5.26, p = 0.02), total mammograms read (chi 2 5.86, p = 0.05), and mammograms read per year (chi 2 8.07, p = 0.01) significantly correlated with a sufficient test. DISCUSSION: The evaluated sample is rather large but not necessarily representative of Italian radiologists. Had the sample been selected, there is no way to know if the results would have been biased towards a better or worse figure with respect to the national average. A significant correlation was found with reading experience (the best results were obtained by operators with > 10,000 films read and with > 2,000 films read/year), as which is important because most Italian radiologists reporting mammography usually read a limited number of cases. CONCLUSIONS: These results on such a wide sample of radiologists, possibly representative of the national average, are disappointing, and suggest that the average quality of mammography reporting in Italy may not be up to standards. Thus, we suggest that quality control program for clinical mammography not only test the equipment but include training and accreditation of radiologists.
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OBJECTIVES: To estimate overdiagnosis (detection of latent carcinomas) as a consequence of screening for prostate cancer. DESIGN: Based on actual screen (first or repeat) detected and interval prostate cancer rates observed in the Florence screening pilot study, a scenario was simulated where males aged 60 years (or 65) had six biennal screens and were followed up for four years. Overdiagnosis was determined as the proportional excess of cancers detected by screening with respect to that expected in its absence. SETTING: City of Florence, Italy, from 1992 through 1995. POPULATION: 2,740 resident males, aged 60 to 74 years. RESULTS: Overdiagnosis was estimated to be 51% (95% confidence limits: 44%-55%) or 93% (85%-101%) for age 60 or 65 at entry. Comparison with other screening experiences obtaining higher detection rates suggests that a more aggressive screening approach could be associated with overdiagnosis estimates as big as 200%-250%. CONCLUSIONS: Screening for prostate cancer is associated with a relevant risk of overdioagnosis. As latent carcinomas can not be presently identified, this would lead to overtreatment in most overdiagnosed cases. The negative consequences of overdiagnosis (knowledge of having a cancer) and of overtreatment (impotence, incontinence, perioperatory death) may be extremely serious. In absence of any scientific evidence of screening benefits (if any) screening should not be recommended as a current practice, but should be limited to prospective controlled studies designed to assess its cost-effectiveness.
The aim of our case-control study was to estimate the effect on mortality from colorectal cancer (CRC) of a population-based screening with a faecal occult blood test started in 1982 in a rural area of the district of Florence. We examined the relationship between mortality and the interval since the most recent screening. The cases in the study were 206 individuals who had died from CRC after the age of 41 years. Five controls were selected randomly from the list of individuals alive at the time of diagnosis of the corresponding case and were matched by sex, age and place and length of residence. After adjustment for potentially confounding factors, the odds ratio (OR) for death from CRC for screened persons vs. those not screened was 0.60 [95% confidence interval (CI), 0.4-0.9]. The OR was lowest in the first 3 years after the most recent test (OR = 0.54; 95% CI, 0.3-0.9) and increased towards unity subsequently. Our results suggest that screening for CRC by biennial faecal occult blood testing can reduce mortality from the disease.
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BACKGROUND: The widespread belief that fibroadenoma is associated with an increased risk of subsequent breast cancer is based on studies of histologically-confirmed fibroadenomas. In current practice only a minority of fibroadenomas are excised; most of them are diagnosed on the basis of palpation and imaging, and are not surgically removed. The decision for surgical excision may be influenced by the presence of individual risk factors, and this can act as a confounder and bias studies that are based only on surgically excised fibroadenomas. PATIENTS AND METHODS: To investigate this hypothesis we linked data from a consecutive series of 3938 fibroadenomas diagnosed histologically (n = 1335) or clinically (n = 2603) in women aged 30 to 69 years to the Tuscany Cancer Registry database. After exclusion of concurrent breast cancers or cancers occurring within six months after the diagnosis of fibroadenoma, the observed and expected incidence of subsequent breast cancer were compared. RESULTS: The overall Standardized Incidence Ratio (SIR) for excised and non-excised fibroadenomas was 1.38 (95% CI = 1.1-1.7). The SIR for histologically-confirmed fibroadenomas was 2.0 (95% CI 1.4-2.7) whereas there was no apparent risk for non-excised fibroadenomas (SIR = 0.97, 95% CI = 0.7-1.4). CONCLUSION: This study suggests that assessment of breast cancer risk subsequent to a diagnosis of fibroadenoma may be biased if the analysis is limited to surgically-excised fibroadenomas.