Search PubMed⌕ Search

Biomedical subjects

R Bonardi

Publications and source records attributed to R Bonardi.

86 records · Page 5Linked to original sources
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗
PubMedDate not supplied

Reliability of volume or age-adjusted prostate specific antigen to improve diagnostic accuracy.

Prostate Specific Antigen (PSA), PSA density, PSA excess, and PSA age-specific range have been compared in 331 subjects (35 cancers, 296 benign) with equivocal findings at screening by PSA or palpation+transrectal ultrasonography. The specificity of PSA using a cut-off of 4 ng/ml was only 0.49. A cutoff of 10 ng/ml improved the specificity to 0.88 but the sensitivity decreased from 0.97 to 0.63. The sensitivity and specificity for PSA density (cutoff 0.15), PSA excess (cutoff -5), and age-specific range were 0.86 and 0.80, 0.80 and 0.82, and 0.91 and 0.67, respectively. Avoided benign biopsies vs missed cancers on the basis of PSA density, PSA excess and PSA age-specific range would have been 19 and 5, 26 and 7, and 16 and 3, respectively. Methods adjusting for prostate volume allow a better interpretation of PSA values and may reduce the benign biopsy rate, but the consequent cost of delayed cancer diagnoses when the choice of biopsy is based only on these methods seems unacceptable.

Age Factors↗
PubMedDate not supplied

[The assessment of the impact of a double reading by expert readers in a mass mammographic study].

PURPOSE: To evaluate the role of double reading of screening mammograms by expert radiologists. MATERIAL AND METHODS: We analyzed the results of independent readings of a proficiency test of screening mammography (140 cases, 32 cancers) performed by four expert radiologists. Double reading was simulated by matching the four original readings in 6 possible combinations. The impact of double reading over single reading was evaluated in terms of increased sensitivity and increased recall rate. RESULTS: Of 32 carcinomas 22, 6, or 4 were identified by 4, 3, or 2 readers, respectively. Of 108 cases negative for cancer a recall for further investigations was suggested by 4, 3, 2, 1 or no reader(s) in 3, 3, 9, 14, or 79 cases, respectively. Inter-reader diagnostic repeatability was good (k = 0.65). Single readers achieved an average sensitivity of 89% (range 87.5-90.6%) and an average recall rate of 12.2% (range 7.4-16.6%). Simulated double reading achieved an average increase in sensitivity of 8.8% (range 6.2-10.95%) and an average increase of recall rate of 6.2% (range 3.8-8.3%). CONCLUSIONS: Even though the relative increase of recall rate is relevant (+53.2%), the corresponding gain in sensitivity justifies the use of double reading, which was confirmed to be worthwhile also when expert radiologists are involved. This study confirms the opportunity of adopting double reading as a routine procedure in mammographic screening.

Aged↗
PubMedDate not supplied

[Impact of replacement hormone therapy in menopause on breast radiologic density and possible complications of mammography in the assessment of breast masses].

PURPOSE: To analyse the association of hormone replacement therapy (HRT) and radiological density, defined as the fraction of breast volume occupied by fibroglandular opacity. MATERIAL AND METHODS: We considered 678 postmenopausal women, consecutively undergoing mammography within an organized screening program, 188 (27.7%) of whom were receiving HRT. Attribution of radiological density was performed prospectively and blind as to HRT status. RESULTS: Both radiological density (p = 0.12) and exposure to HRT (p < 0.001) were found to correlate with age (younger women are more likely to use HRT and to have denser breasts, even without HRT) so the analysis of the correlation between HRT and radiological density was adjusted for the possible confounding effect of age. After stratification by age group, univariate analysis showed a significant correlation between HRT and radiological density (density = > 50%: HRT+ = 34.0%, HRT- = 17.6%: F-value 18.86, df = 1, p < 0.001). Also the duration of HRT was significantly associated to radiological density (Pearson coeff. = 0.12: p = 0.0011). Multivariate analysis adjusting for the confounding effect of age showed an increased risk of dense breast (17% or 7% for a radiological density > 25% or > 50%, respectively) in HRT users with respect to non users. DISCUSSION: The study design, the adoption of a classification of breast density less exposed to intraobserver variability and multivariate analysis of a large series, allows a reliable evaluation of the association of HRT to breast density. As no threshold value is known for the masking effect of density on breast cancer, the negative effect of HRT on screening sensitivity cannot be accurately quantified. CONCLUSIONS: This study confirms the effect of HRT on radiological density in postmenopausal women, suggesting a possible reduction of screening sensitivity and efficacy. Such a hypothesis still needs validation by means of a prospective analysis of the correlation between HRT and the frequency of interval cancer occurrence (the best indicator of sensitivity).

Aged↗
PubMedDate not supplied

Laboratory evaluation of the patient with liver disease.

Because the liver performs multiple functions, no single laboratory test or battery of tests is sufficient to provide a complete estimate of the function of the liver in every clinical situation. A broad array of biochemical tests are used to assess the many functions of the liver and to evaluate patients with suspected or established liver disease. These tests are referred to collectively as "liver function tests" (LFTs). LFTs are used to screen people for the presence of liver disease, suggest the underlying cause, estimate the severity, assess prognosis, and monitor the efficacy of therapy. Abnormal LFTs may be the first indication of sub clinical liver disease and may thereby guide further diagnostic evaluation. After the existence of hepatic dysfunction is recognized, the specific pattern of liver test abnormalities may suggest the category of the underlying liver disease, such hepatitis, biliary obstructions, or infiltrative liver disease. The value of screening healthy, asymptomatic persons for liver disease with the use of LFTs is controversial and may not be cost-effective. If screening is performed a panel of tests (e.g., AST, alkaline phosphatase, bilirubin, albumin) is preferable to using a single test because of superior sensitivity and specificity for liver disease and lower cost than the sum of individually performed tests.

Humans↗
PubMedDate not supplied

[Bone metastasis of hepatocarcinoma. Review of the literature, radiologic pictures and personal caseload].

Prognosis of patients affected with hepatocellular carcinoma (HCC) has been improved by the modern imaging techniques allowing an early diagnosis and by the value of the therapeutic protocols employed. Staging has also become more and more important. Bone metastases from HCC are reportedly rare. The authors observed a 5.5% incidence in 90 cases of hepatocarcinoma. The metastases were demonstrated by radiography, CT, and nuclear scintigraphy, in patients with skeletal pain. The plain film appearance of skeletal metastases from HCC was osteolytic in all cases; no surrounding sclerosis was seen. CT scans demonstrated the destructive nature of these lesions, which were associated with bulky soft-tissue masses. Metastases exhibited increased radiotracer (99mTc-MDP) uptake at bone scintigraphy. The authors believe that bone scintigraphy should be included in the staging protocols of the HCCs which need a potentially curative therapy.

Aged↗