Follow-up of colorectal cancer.
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Colorectal Neoplasms↗
Biomedical subjects
S Ciatto
Publications and source records attributed to S Ciatto.
Time trends of benign/malignant breast biopsy ratios a multicenter Italian study.
AIMS AND BACKGROUND: Although they have been decreasing over time due to improved specificity of diagnostic assessment, benign biopsies of the breast are still common. Benign biopsies should be regarded as negative events, due to their economical and psychological cost and their possible negative impact on cosmesis and on further diagnostic evaluation. METHODS: Retrospective data on benign/malignant breast biopsies ratio (B/M) were collected in 9 Italian centers for a period of 10-15 years. The time trend of B/M and its association to age or to single centers was evaluated. RESULTS: Overall 31,001 cases were considered. A strong association of B/M to age was evident (average B/M values were 5.0, 1.3, 0.6, and 0.2 for women aged < 40, 40-49, 50-59, and > 59 years). A significant trend of decreasing B/M over time was observed only for one center. Age standardized B/M was significantly different (P < 0.000001) between centers, ranging between 0.34 and 1.69. Multivariate analysis confirmed an independent significant association of age and center to B/M. CONCLUSIONS: Marked differences in B/M are evident between centers, which cannot be explained by the confounding effect of age or by any apparent difference in the diagnostic protocol. The observed differences are likely ascribed to individual variations in diagnostic aggressivity. A progressive increase of the predictive value of calls for surgical biopsy may be achieved over time and centers with a high B/M should make every effort to optimize their performance. Acceptable (< 40 = 5, 40-49 = 1.5, 50-59 = 0.75, > 59 = 0.3) and desirable (2.5, 0.75, 0.35, 0.15) age specific reference standards for B/M are proposed.
Adult↗
Training in colposcopy: experience with a videocolposcopy test.
The authors evaluate the results of a videocolposcopy test (330 total cases, 12 cases of histologically confirmed CIN2 or more severe lesions) taken by 9 accredited and 17 unaccredited colposcopists during 1995. Seven of 9 accredited and 4 of 13 unaccredited colposcopists reached the requested standard (sensitivity > 90%, biopsy rate < 60%). Performance was definitely better when the test was not blind to the cytologic report (4 of 13 reached the requested standard) with respect to blind reading (none of 17). The study confirmed that colposcopy at unaccredited practices is poorly accurate. Colposcopic assessment of patients with abnormal smears should be centralized in accredited practices, which should undergo periodic quality control to guarantee screening efficacy. Tape-recorded videocolposcopy tests are a good, simple, practical and inexpensive method for interobserver quality control of colposcopic performance.
Clinical Competence↗
Lack of prognostic value of p53 protein expression in node-negative breast cancer.
AIMS AND BACKGROUND: The association of p53 protein accumulation and prognosis in node-negative breast cancer patients has been alternately demonstrated and denied in literature reports, and opinions on the use of p53 expression as an indicator of high risk of recurrence and as a guide for adjuvant therapy are controversial. STUDY DESIGN: The association of p53 protein accumulation with prognosis was retrospectively evaluated in a series of 221 node-negative breast cancer patients treated with surgery alone and followed up for a minimum of 10 years. p53 accumulation was determined by immunohistochemistry on archive material, and classified into four grades of increasing immunostaining. RESULTS: No association was observed between p53 and age or pT category, whereas a significant association with nuclear grade was found (P = 0.0014). Univariate and multivariate analysis of 10-yr disease-free and overall survival showed a significant and independent prognostic association for tumor size (pT category) and nuclear grading but not for p53 expression, whatever grade grouping was used. CONCLUSIONS: We did not find any evidence supporting the use of p53 immunostaining in current practice as an independent prognostic indicator or as a discriminant factor for adjuvant treatment of node-negative breast cancer patients.
Adult↗
Comparing two modalities of management of women with cytologic evidence of squamous or glandular atypia: early repeat cytology or colposcopy.
Early repeat cytology is recommended in most screening programs for cervical cancer in subjects with squamous or glandular abnormalities not amounting to neoplasia (atypical squamous cells of undetermined significance, ASCUS), but immediate colposcopy is also recommended in some countries, especially those where there is easy access to colposcopic facilities. We evaluated the cost-effectiveness of the two procedures in a prospective study of women with cytologic ASCUS, invited to cytocolposcopic assessment after 6 months. Colposcopy-directed biopsy was assumed as the gold standard, and the accuracy of colposcopy at 6 months was assumed to be equal to that of immediate colposcopy. Out of 874 compliers, punch biopsy was performed in 303 cases (34.7%), and 19 CIN2+ lesions were detected (CIN2 = 12, CIN3 = 6, microinvasive carcinoma = 1). Detecting 13 CIN2+ lesions at colposcopy required 874 colposcopies and 303 directed biopsies: the cost per CIN2+ lesion detected with the procedure was 2,749 US$. Detecting 15 CIN2+ lesions at repeat cytology required 874 cytologic examinations, 137 colposcopies, 64 directed biopsies, and 6 diagnostic large-loop resections, the latter being performed in subjects with high-grade squamous intraepithelial lesion and less severe lesions at punch biopsy: the cost per CIN2+ lesion detected with the procedure was 1,961 US$. The policy of repeat smear was more cost-effective than immediate colposcopy. According to such results, the protocol of the Florence screening program has been modified since October 1996.
Adult↗
Colposcopy as a primary screening test for cervical cancer.
AIM AND BACKGROUND: To evaluate the cost effectiveness of screening by colposcopy compared to conventional cytology. METHODS: A prospective study was performed in the Florence District screening center on 3,000 consecutive women, self referring, who were examined by cytology and colposcopy in a blind fashion. Further assessment was based on cytologic report or on colposcopy-directed punch biopsy. Actual costs of the whole screening process were known. The cost effectiveness of different possible simulated screening scenarios was then determined. RESULTS: Overall, 18 high-grade lesions (CIN3 = 9, CIN2 = 9) were detected. Four different screening scenarios were compared, namely a) cytology alone, b) cytology + repeat smear for ASCUS (atypical squamous cells of undeterminate significance) cases, c) colposcopy + cytology for cases of condyloma at punch biopsy, and d) colposcopy alone. Although they had a higher cost per examined woman (a) = 17.98, b) = 19.40, c) = 23.86, d) = 22.10 US$), scenarios c) and d) had a higher relative sensitivity (a = 44.4, b = 61.1, c = 100, d = 88.8%) and a lower cost per high-grade lesion detected (a = 6,743, b = 5,291, c = 3,977, d = 4,144 US$). CONCLUSIONS: Screening by colposcopy is a feasible procedure which is more sensitive and more cost effective than conventional cytology screening. At least in those settings where access to cytopathology may be difficult, screening by colposcopy should be considered as a possible alternative.
Adult↗
Analysis of false-negative and underreported smears in the Florence district screening program for cervical carcinoma.
AIMS AND BACKGROUND: To review false-negative or underreported (reactive changes, squamous or glandular atypia) smears performed in women developing histologically proven CIN2 or more severe lesions within 24 months and evaluate error causes. The study setting was the Florence District cervical cancer population-based screening: about 60,000 women age 25-60 years screened per year. METHODS: 118 false-negative or underreported cases were identified at screening files-cancer Registry matching, and the original smears were reviewed by six independent readers to judge smear adequacy and error type. RESULTS: Sampling errors (reported as inadequate, negative or less severe than CIN1 at review) accounted for 74% and screening/interpretation errors (reported as CIN1 or more severe at review) accounted for 26% of studied cases. Screening/interpretation errors were more likely ascribed to misinterpretation and underreporting than to misperception of cellular abnormalities. CONCLUSIONS: Quality control should above all address the problem of sampling adequacy. Due to the rarity of misperceived abnormalities (true screening errors), manual or automated rescreening of negative smears would not be an effective procedure for quality control.
Adult↗
Risk of endometrial cancer in breast cancer patients under long-term adjuvant treatment with tamoxifen.
AIMS: To evaluate the relative risk of endometrial cancer with respect to the expected underlying incidence in breast cancer patients undergoing long-term adjuvant tamoxifen therapy. METHODS: A total of 1010 postmenopausal breast cancer patients receiving adjuvant tamoxifen and with a first negative endometrial ultrasonography (cutoff for abnormal endometrial thickness >5 mm) were followed by annual transvaginal ultrasonography. Abnormal endometrial thickness prompted an outpatient endometrial biopsy or curettage under anesthesia in the case of cervical stenosis and increasing endometrial thickness. The standardized incidence ratio (SIR) with respect to underlying incidence was determined. RESULTS: A total of 1,010 eligible subjects who had been receiving tamoxifen for an average of 51 months were enrolled and followed for a total of 2,361 patient-years between January 1993 and December 1996. Five cases of endometrial cancer were observed in the study period: 1 was detected at screening, and 4 were diagnosed for vaginal bleeding in the interval between screening examinations. SIR was 4.0 (95% confidence interval, 1.3-9.4) and increased to 4.8 (CI, 1.6-10.5) when the single cancer detected at first screening was considered as incident. CONCLUSIONS: This study adds evidence to the hypothesis that long-term tamoxifen treatment may be responsible for a relevant increase in the risk of developing endometrial cancer. Surveillance based on endometrial ultrasonography was poorly sensitive, but the favorable stage at diagnosis of screen-detected or interval endometrial cancers does not support a more aggressive screening approach.
Aged↗
Benign breast surgical biopsies: are they always justified?
AIM OF THE STUDY: To evaluate the indications for open surgical biopsy of breast lesions resulting in a benign histologic report. METHODS: A consecutive series of 754 benign breast biopsies was collected from six Italian centers previously participating in a multicenter study on the benign/malignant biopsy ratio. Histologic diagnosis, diagnostic tests performed, final clinical diagnosis and the indication for surgical biopsy were compared. RESULTS: Fibrocystic alterations represented the most frequent histologic type (43.2%), followed by fibroadenomas (34.5%). Atypical hyperplasia, phyllode tumors and cancer-like lesions (radial scar, sclerosing adenosis) accounted for a minority of cases. The diagnostic approach was different among centers, with mammography, ultrasonography or cytology being underused in some of them. Suspicion of cancer was an indication for surgical biopsy in 66.7% of cases. In the remaining cases the final report was negative or benign, but biopsy was advised for growing lesions (11.3%) or for cosmetic (3%) or psychological reasons (8.2%). In 4% of cases surgical biopsy was presumably advised for the concurrent influence of high-risk conditions such as previous breast cancer (0.7%), family history of breast cancer (2%) or contralateral synchronous breast cancer (1.3%). In 6.8% of the cases biopsy was advised elsewhere for unknown reasons. The indications for biopsy differed among centers, with one center having a low rate of suspicious cases (37%) and a high rate of reported "cosmetic" or "psychological" reasons (47%). CONCLUSIONS: Leaving aside differences in diagnostic approach and aggressiveness, two thirds of all lesions were biopsied in order to exclude cancer. The routine use of a more complete diagnostic protocol and/or alternative methods to obtain a histologic diagnosis (e.g. core biopsy) might substantially reduce the need for open surgical biopsy.
Adolescent↗
A first survey of organized cervical cancer screening programs in Italy. GISCi working group on organization and evaluation. Gruppo Italiano Screening Citologico.
In Italy, where no national screening program for cervical cancer exists, organized programs have developed on a local basis. We performed the first survey of existing organized programs by mailing a standard questionnaire to a large network of possibly involved services. For the present survey, a program was defined as organized if personal invitations were sent. We identified 29 already active organized programs and 4 others in a starting phase. The target population of active programs included 2,074,820 women in the age range 25-64 years, corresponding to 13.5% of the Italian female population of the same age. The situation is rapidly evolving since many regional programs are being implemented. Most programs followed Italian and European recommendations as regards the age limits, interval between screening rounds, presence of a fail-safe system for women referred for colposcopy, presence of protocols for diagnostic workup and treatment, and presence of referral centers for such phases. However, many programs did not meet national guidelines as regards the size of laboratories interpreting smears, which were frequently small. Second-level referral centers also frequently had a very small activity. The average (weighted for size of the invited population) compliance to invitation and coverage (proportion of women with at least one test in the last 3 years) was 32.6% and 66.0%, respectively, therefore needing to be improved. Compliance to colposcopy (weighted for number of referred women) was 81.4%. We found a very high variability in the proportion of women referred for colposcopy that could only be partly explained by different referral protocols and could depend on different criteria of smear interpretation: the average (weighted for number of tested women) was 2.01%. A need for improvement in the process of evaluation and for homogenization of criteria of cytology interpretation was identified: work in this regard is on-going.
Adult↗
Measurement of the cost of screening for cervical cancer in the district of Florence, Italy.
AIMS AND BACKGROUND: To estimate the cost per woman examined and per CIN II or more severe lesion detected in a population-based cytologic screening program for cervical cancer prevention. An organized cytologic screening program has been ongoing in the Florence District since 1973, and a call-recall system using mail invitation has been ongoing since 1980. Smear reading and assessment of screening positives is centralized at the screening unit. METHODS AND STUDY DESIGN: All relevant resources (costs) consumed by the program were listed and measured. The unit cost per examined woman and per each CIN II or more severe lesion detected was estimated for each screening phase (recruitment, screening, assessment). RESULTS: The cost per examined woman was $24.60, whereas that per CIN II or more severe lesion detected was $13,600. Staff accounted for 80% of total amount. CONCLUSIONS: Although the cost for a single procedure is low, the cost per detected lesion is quite remarkable due to the low detection rate in a population screened for a long time. Different approaches and longer interval screening tests are discussed.
Adult↗
Screening for prostate cancer by PSA determination: a time for caution.
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Aged↗
Predicting prostate biopsy outcome by findings at digital rectal examination, transrectal ultrasonography, PSA, PSA density and free-to-total PSA ratio in a population-based screening setting.
The study offers a retrospective analysis of the positive predictive value (PPV) of several variables, i.e. digital rectal examination (DRE), transrectal ultrasonography (TRUS), PSA value, PSA density (PSAD), and free/total PSA ratio (F/T), for the histologic outcome of 179 prostate biopsies performed within a population-based screening trial. The ratio of spared benign biopsies to missed cancers (SBB/MC) if biopsy results had been decided on the basis of single variables was also evaluated. PPV was 82.9% for DRE, 56.3% for TRUS, 26.6% for PSA (cutoff > or =4 ng/mL), 47.4% for PSA (cutoff > or =10 ng/mL), 42.0% for PSAD (cutoff 0.15), 59.2% for PSAD (cutoff 0.20), 34.9% for F/T (cutoff 0.20) and 40.0% for F/T (cutoff 0.15). SBB/MC was 121/23 for DRE, 96/12 for TRUS, 11/10 for PSA (cutoff > or =4 ng/mL), 107/34 for PSA (cutoff > or =10 ng/mL), 87/23 for PSAD (cutoff 0.15), 109/26 for PSAD (cutoff 0.20), 45/8 for F/T (cutoff 0.20) and 70/14 for F/T (cutoff 0.15). Multivariate analysis of the association with biopsy outcome showed the highest odds ratio for TRUS (13.24, 95% CI=4.4-30.7), and considerably lower values for DRE (4.17, 95% CI=2.0-8-9), PSAD (cutoff 0.20: 3.24, 95% CI=-1.8-5.7) and F/T (cutoff <0.15: 3.16, 95% CI=1.7-1.8). None of the possible variable combinations was clinically useful: the highest PPV (83.3%) was obtained with a combination of suspicious DRE/TRUS, PSAD >0.20 and F/T <0.15, which nevertheless missed 20 of 52 cancers.
Biopsy↗
Analysis of PSA velocity in 1666 healthy subjects undergoing total PSA determination at two consecutive screening rounds.
The study purpose was to assess PSA velocity (PSAV) in healthy subjects in order to establish a reliable cutoff for the differential diagnosis of prostate cancer in a screening setting. We studied a series of 1666 healthy men aged 55 to 74 years undergoing two total PSA determinations at a four-year interval within a population-based randomized screening trial at the Centro per lo Studio e la Prevenzione Oncologica of Florence. First and second screening round PSA assays (PSA1 and PSA2) were carried out with the same method and by the same laboratory. PSAV (PSA1-PSA2/year) was determined in non-cancer subjects in the overall series or in specific age and PSA subgroups, and in subjects with cancer detected at the second screening round. Average PSAV in 1648 non-cancer subjects was 0.07 ng/mL/year (range -2.18+5.99, 95% CI 0.05-0.09); at least one third of subjects showed a decrease in PSA (negative PSAV), mostly of limited magnitude and in the low PSA range. Average PSAV in the 18 cancer patients was 1.16 ng/mL/year (range 0.10-5.6, 95% CI 0.56-1.77), which is significantly higher (p<0.01) than in non-cancer subjects. None of the cancer patients showed a PSA decrease over time. Whatever cutoff was taken for PSAV, its power to discriminate cancer was limited: in particular the previously used PSAV cutoff of 0.75 ng/mL/year would have included only 42 of the 1648 non-cancer subjects (specificity 97.5%) but excluded eight of the 18 cancer patients (sensitivity 55.5%). At best, with the adopted screening protocol PSAV (cutoff 0.10 ng/mL/year) could have spared 27.9% of non-cancer subjects with PSA > or =2.5 ng/mL further diagnostic assessment and 22.7% of non-cancer subjects with PSA > or =4 ng/mL random sextant biopsy, while missing no cancers. This study provides a reliable estimate of PSAV based on a large unbiased population sample. PSAV is widely variable over time, particularly at low PSA values. PSAV might be of value as an indicator for diagnostic assessment and random sextant biopsy in a screening setting.
Aged↗
Italian national consensus conference on prostate cancer screening (Florence, May 17, 2003)--final consensus document.
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Biomarkers↗
Predictors of random sextant biopsy outcome in screened men with PSA > 4 ng/mL and a negative sextant biopsy at previous screening. Experience in a population-based screening program in Florence.
The aim of this study was to evaluate possible pedictors of the outcome of repeat random sextant biopsy of the prostate prompted by a rise in prostate-specific antigen (PSA). Random biopsies performed for PSA elevation (>4 ng/mL) in the course of a randomized study of screening efficacy were reviewed, and 87 consecutive biopsies (carcinoma = 13, high-grade prostatic intraepithelial neoplasia = 6, negative = 68) performed in subjects with a negative random biopsy at the previous screening round were considered. Findings at digital rectal examination or transrectal ultrasonography and total PSA value were not useful predictors of repeat biopsy outcome, whereas PSA velocity was significantly associated with biopsy outcome. The positive predictive value for a cancer biopsy was 2.7% (1/36), 28.5% (2/7), and 22.7% (10/44) for PSA velocity values of <0.1, 0.1-0.19, and >0.19 ng/mL/yr, respectively. A cutoff of 0.1 ng/mL/yr for PSA velocity would have allowed to avoid approximately half (35/74 = 47.2%) of the benign biopsies while decreasing the sensitivity by 7.6% (1/13), and is thus suggested as a possible criterion for the indication of repeat random biopsy for persistent PSA elevation.
Aged↗
Association of human papillomavirus with prostate cancer: analysis of a consecutive series of prostate biopsies.
The study purpose was to investigate the association of human papillomavirus (HPV) infection with prostate cancer. The presence and type of HPV DNA were investigated by polymerase chain reaction in the preservation fluid of 60 consecutive prostate core biopsies (29 benign, 31 malignant). The material was inadequate (no DNA found at beta-globin testing) in four benign and five cancer biopsies. HPV DNA was found in 17 of 26 (65.3%) cancer and 12 of 25 (48.0%) benign biopsies (chi2 = 0.94, p = 0.33). High-risk HPV type positivity was observed in 14 of 26 (53.8%) cancer and in five of 25 (20.0%) benign biopsies (chi2 = 4.38, p = 0.03). Twenty-three of 29 cases were positive at L1 region testing with MY09/11 primers; testing with primers directed to the E6/E7 region revealed six further HPV-positive cases (four cancer, two benign). The presence of HPV in prostate tissue suggests a possible reservoir for sexual transmission of types with oncogenic potential. Our findings also suggest a possible role of high-risk HPV infection in the etiology of prostate cancer and encourage further research into this issue.
Aged↗
Evaluation of diagnostic accuracy of screening by fecal occult blood testing (FOBT). Comparison of FOB Gold and OC Sensor assays in a consecutive prospective screening series.
We evaluated a new immunological fecal occult blood testing assay (FOB Gold, Sentinel = SENT) compared to the assay currently employed in the Florence screening program (OC-Hemodia, Eiken = OC). A total of 4,133 subjects were screened with both tests and underwent colonoscopy if positive (100 ng/mL Hb cutoff) to either test: 190 (4.59%) were positive (OC =140 (3.4%); SENT = 131 (3.2%)). The relative sensitivity for 7 cancers was 100% with OC and 67.9% with SENT, and for 48 high-risk adenomas (HRAs) it was 77.0% with OC and 66.6% with SENT. The positive predictive value (PPV) for cancer+HRA was 31.4% for OC and 28.2% for SENT and the specificity was 97.7 for both. The differences were not statistically significant. Adding SENT to OC increased the positivity rate by 32% and the cancer+HRA detection rate by 25%, and decreased the PPV by 10%. Both tests were performed on the same tubes in 1,601 cases, and in 18 of 47 cases they differed on different tubes but not on the same tube, suggesting inhomogeneous Hb content or varying fecal matrix influence in different samples. SENT has practical advantages for screening [corrected] (fully automated, high output, requires no dedicated instrument), a comparable specificity and a lower sensitivity, though the latter difference may be partially ascribed to differences in sampling and not to the assay itself [corrected] Because of the statistical insignificance of the differences, further studies are needed for confirmation.
Adenoma↗