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R Bonardi

Publications and source records attributed to R Bonardi.

At least 19 recordsLinked to original sources

Minority report - false negative breast assessment in women recalled for suspicious screening mammography: imaging and pathological features, and associated delay in diagnosis.

AIM: We studied imaging, pathology and diagnostic aspects of false negative assessment (FNA) in women recalled for suspicious screening mammography. METHOD: Subjects were women aged 50-69 years undergoing biennial screening mammography within the Florence District screening programme from January 1992-December 2001 (339,953 consecutive screens). We identified all cancers occurring in women recalled to assessment and ascertained, and reviewed, all cases considered as negative on assessment and subsequently diagnosed with breast cancer. We compared imaging features, tumour histology and stage, and diagnostic testing on assessment for all women with cancer, and presentation and length of delay in women falsely negative on assessment. RESULTS: Eleven thousand six hundred and twenty four women were recalled to diagnostic assessment (recall rate = 3.4%) predominantly for suspicious mammography (9,216 positive screens). Breast cancer was missed in 57 cases: a FNA rate of 0.50% (0.37-0.62%) and comprising 4.1% (3.0-5.1%) of cancers occurring in women recalled after a positive screen. Two types of abnormalities were significantly more frequent in FNA cases than cancers detected at assessment: mass with regular borders (21.1 vs. 5.6%, p = 10(-5)), and asymmetrical density (22.8 vs. 5.4%, p = 10(-5)). On review 56% of FNAs were benign or probably benign BI-RADS categories. FNA occurred in 1.4% of early recalls and in 0.4% of initial assessment (p=0.0001). Significantly fewer tests were performed when assessing missed cancers than detected cancers with the most significant difference noted for FNAC (29.8 vs. 96.0%, p=10(-6)); mammography as the only evaluation on assessment was more frequent in missed cancers (31.5% vs 0.2%, p = 10(-6)). The 57 missed cases were subsequently diagnosed at early recall (2 cases), next biennial screen (11 cases), or as interval breast cancers (44 cases) with a mean delay in diagnosis of 628 days. Tumour histology, size and nodal status did not significantly differ between cancers missed and cancers diagnosed on assessment. CONCLUSION: False negatives on assessment represent a minority group in whom screening has failed. They might be reduced by adopting a more intensive diagnostic approach to assessment. Although there was no evidence of a worse prognosis in cancers missed at assessment, the delay in diagnosis is substantial and may impact long-term outcomes.

Aged↗

[Non-invasive diagnosis of Helicobacter pylori infection in the 2006 clinical practice].

At present, 2 approaches are used to detect Helicobacter pylori (H. pylori): invasive, if based on biopsies taken during endoscopy, and non-invasive, if they do not rely on endoscopic approach. A 3rd option is offered by the string test, that employs an invasive non-endoscopic strategy. The present review attempts to update on the diagnostic non-invasive approaches to patients in the clinical setting. Non-invasive tests include urea breath test (UBT), antigen stool assay, serology, and ''doctor's tests''. The choice of the methods depends on the situation, for example, the clinical circumstances, the diagnostic accuracy, the costs of the testing strategy, and the availability of the tests in the respective area. According to European guidelines, UBT and antigen stool assay are recommended in patients without alarm symptoms or under 45 years of age, at low risk of malignancy in the test and treat strategy. Confirmation of H. pylori eradication following treatment should be tested by UBT; the stool antigen assay is the alternative if the former is not available.

Antigens, Bacterial↗

Florence-Sydney Breast Biopsy Study: sensitivity of ultrasound-guided versus freehand fine needle biopsy of palpable breast cancer.

BACKGROUND: Fine needle aspiration biopsy (FNAB) is widely used in the diagnosis of breast cancer. It is unknown whether, for palpable cancers, ultrasound-guided FNAB is more accurate than freehand FNAB, and practice varies between physicians, services and countries. METHODS: From consecutive women attending a major cancer centre in Florence, we prospectively recruited subjects who had a definitely palpable lump which was solid on ultrasound and suspicious of malignancy (n = 102). All subjects were investigated using both ultrasound-guided and freehand FNAB (one aspirate with each method). Radiologists skilled in both sampling techniques performed all clinical examinations and aspirations, and for each subject the same radiologist obtained both FNAB samples. Sequence of aspiration method was randomised. Cytological interpretation was blinded to method of sampling. Comparative sensitivity (and insufficiency) for FNAB using the two methods was calculated in all cancers (n = 97). RESULTS: Ultrasound-guided FNAB resulted in 13.6% (5-22%) less insufficient aspirates than freehand FNAB (chi2 = 7.58; p = 0.006). When insufficient aspirates are included and considered as negative, ultrasound-guided FNAB has a 14.6% (5.8-23%) or a 16.5% (7.6-25.4%) significantly better sensitivity than freehand FNAB (for cytology 3-5 positive or cytology 4-5 positive respectively). When insufficient aspirates are excluded from the analysis, ultrasound-guided FNAB has a 1.4% (-1.2 to 3.9%) or a 2.6% (-2.5 to 7.8%) higher sensitivity than freehand FNAB (for cytology 3-5 positive or cytology 4-5 positive respectively) but this difference in the sensitivity of the two methods is not statistically significant. CONCLUSION: Our data suggest that ultrasound-guided FNAB has better sensitivity than freehand FNAB in palpable breast cancer, which is predominantly an effect of a significant reduction in insufficient aspirates, but in part an effect of 'upgrading' cytological classification of cancers.

Adult↗

Second reading of screening mammograms increases cancer detection and recall rates. Results in the Florence screening programme.

OBJECTIVE: To assess double reading effectiveness in mammography screening. DESIGN: Retrospective study of 177,631 consecutive mammograms double read during 1998-2003. SETTING: The Florence screening programme, involving 11 trained radiologists. Abnormalities reported by at least one reader prompted assessment. RESULTS: The referral rate was 2.89% for the first reader, 3.15% for the second reader, and 3.59% for either reader. Of 713 total cancers detected, 43 were suspected only by the second reader (6.4% relative, 0.024% increase in absolute detection rate) and had a lower stage compared to the first reader (pTis-pT1b = 65.7 versus 52.0%): 41 were reviewed and classified (error type) as "minimal sign" in six, and "screening error" in 35 cases, or as BI-RADS 3 in one, 4a in 20, 4b in 13, and 4c in three cases. The second reading cost was 2.70 per woman examined, or 11,168 per additional cancer detected (versus 11,585 at a single reading). DISCUSSION: Second reading is effective in detecting a limited number of additional cancer cases. Tumour stage (one-third over 1 cm in diameter) and review findings (high rate of "screening errors" and BI-RADS R4b-c categories) suggest that second reading detects small "difficult cases" as well as larger cancers missed due to fatigue or loss of attention. Second reading reduces screening specificity to a minor extent, and since cancer detection at second reading seems cost-effective the procedure is recommendable in routine practice.

Aged↗

Autoimmune manifestations during interferon therapy in patients with chronic hepatitis C: the hepatologist's view.

In face of numerous benefits induced by therapy based on interferon (IFN) associated with ribavirin for the treatment of chronic hepatitis C, there is an increasing concern regarding its tolerance, which can, in some cases, reduce the quality of life as well as compliance of patients. Among the less common side effects, there are the autoimmune ones which can be globally divided into appearance or increase in titres of auto-antibodies and/or manifestation of overt autoimmune pathologies. Whereas the former may concern more than 50% of treated subjects, the latter is reported in only 1-2% of patients under therapy. Thyroid dysfunction represents the well-studied autoimmune disorder. The presence of pre-existing anti-thyroid antibodies and being of female sex, constitute relevant risk factors for the development of a disease involving this gland. Often the treatment of thyropathy must be continuous in spite of IFN discontinuation because the disturbance usually does not abate with stopping antiviral therapy. Some observations have pointed out to the fact that IFN can lead to the development of insulin-dependent diabetes mellitus. Sometimes, during, as well as after IFN treatment, the appearance of anti-islet cell antibodies has been shown, but its interrelationship with the development of disease is uncertain. While being treated with IFN for chronic hepatitis C, the finding of non-organ specific antibodies at baseline can increase the likelihood of the development of autoimmune hepatitis. However, their presence does not constitute an absolute contraindication to the treatment, except in case of high titre. Other disorders, such as a lupus erythematosus-like syndrome, haemolytic anaemia, and immune-mediated thrombocytopenia have been reported. In conclusion, although the presence of auto-antibodies is considered to be an epiphenomenon without pathogenic significance in most patients suffering from chronic hepatitis C, it poses a problem when they need to be treated with IFN. This antiviral drug can induce or exacerbate a multitude of autoimmune-related disorders, however, clinically overt immune-mediated diseases are rare and affect a subset of subjects who have an underlying autoimmune diathesis.

Antiviral Agents↗

Monitoring interval cancers in mammographic screening: the Florence District programme experience.

The aim of the present study was to monitor the occurrence of interval (breast) cancers (IC) as an interim outcome measure of quality assurance in the mammographic screening programme of the District of Florence. IC were identified by linking breast screening data with registrations of breast cancers from the Tuscany Tumour Registry. The main outcome measures were the numbers, rates, and the proportionate incidence of IC. Overall, 90 invasive IC were observed among women who attended the breast screening programme in the District of Florence from 1 January 1985 to 31 December 1993, respectively, 23, 50, on 17 cases, at 1, 2, and 3 years after the last negative screening test. Expressed as a proportion of underlying incidence, the figures are 16, 44, and 46%. As to risk factors for IC, mammographic density was the most important one in the present survey, whereas no effect of age emerges from the present study.

Journal Article↗

Transperineal sonography guided biopsy of the prostate: critical review of 1107 cases.

PURPOSE: To assess the predictive value for a positive biopsy of different indicators (rectal examination, transrectal ultrasonography, total PSA, PSA density). MATERIAL AND METHODS: Positive predictive value was assessed on 1107 consecutive US-guided transperineal biopsies performed from 1991 to 2001 (cancer=344, dysplasia (PIN)=64, atypical hyperplasia=4, benign hyperplasia=686, inadequate=9) with univariate and multivariate analysis. RESULTS: Increasing age (chi square for trend 52.2, p <0.001), positive rectal examination (chi square 233, df=1, p<0.001) or ultrasonography (chi square 191, df=1, p<0.001), total PSA (chi square for trend 68.9, p<0.001) and PSA density (cutoff 0.15, chi square 104, df=1, p<0.001; cutoff 0.20, chi square 104, df=1, p<0,001) were all significantly associated to the likelihood of a positive biopsy outcome. Multivariate analysis stresses the independent role of Psa density over total PSA. If the parameters studied had determined the biopsy, spared benign biopsies [positive rectal examination=505 (66%), positive ultrasonography=467 (61%), PSA>4=124 (16%), PSA>10=159 (74%), PSA density >0,15=426 (62%), PSA density >0.20=517 (75%)] would not have justified the amount of delayed cancer biopsies [positive rectal examination=103 (29%), positive ultrasonography=55 (15%), PSA>4=42 (12%), PSA>10=569 (46%), PSA density >0,15=73 (25%), PSA density >0,20=107 (37%)]. CONCLUSIONS: The parameters currently available prior to biopsy, if used alone, allow no reliable prediction of biopsy outcome. Positive predictive value, particularly for PSA density, allows a better evaluation of biopsy indication, particularly for random sextant biopsies in the 4-10 ng/ml PSA range, which are frequently negative.

Adult↗

Decreasing eradicaton rate of Helicobacter pylori infection with metronidazole-based triple therapy. A randomised study.

BACKGROUND: Helicobacter pylori (H. pylori) infection plays an important role in the pathogenesis of duodenal ulcer (DU) disease. Low DU recurrences and reinfection rates were universally described, when treatment was effective. It has been suggested that short-term triple therapy, comprising a proton pump inhibitor plus two antibiotics (clarithromycin, amoxicillin or a nitroimidazole), should be used as first choice in treating H. pylori infection. Nevertheless, conflicting results have been reported on using these treatment regimens in different countries, due to the resistance of H. pylori against one or more antibiotics. Our aim was to compare the efficacy, for H. pylori eradication, of 1-week triple therapy versus 10 and 14-day triple schedules, in patients with a history of recurrent DU. METHODS: A total of 159 patients (85 males, mean age 59.2+/-3.2 years) was randomly treated with a triple therapy including a standard dose of omeprazole twice daily, amoxicillin 1 g twice daily and metronidazole 500 mg twice daily. Fifty-three patients received 1-week triple therapy (Group I), 53 subjects were treated with 10-day triple therapy (Group II) and 53 others with 14-day triple therapy (Group III). H. pylori infection at entry and eradication, at least 4 weeks after therapy had ended, was assessed by 13C urea breath test and histology on biopsies from the antrum and the corpus. RESULTS: Of the 159 subjects randomised into the study, 6 (3 in group II and 3 in group III) were excluded from the per protocol (PP) analysis because of discontinuations. At the end of the course of treatment, the overall H. pylori eradication rate in the intention-to-treat analysis, was 73.5% (39/53) in group I, 71.6% (38/53) in group II and 73.5% (39/53) in group III, without any statistically significant difference. Moreover, the PP analysis also showed no statistical differences, with an eradication rate of 73.5% (39/53) in group I, 76% (38/50) in group II and 78% (39/50) in group III. The reported frequency of side-effects was evenly distributed between the groups, but 6 patients (3.7%) stopped because of adverse events only in groups II and III. CONCLUSIONS: The present study shows that there is no significant difference between the three regimens although the 14-day triple therapy shows a slightly higher H. pylori eradication rate. There is a strong need, in our region, to put forward surveillance programmes to monitor the prevalence of local resistant strains and to guide treatment on the basis of resistance patterns.

Journal Article↗

Interferon and amantadine in combination as initial treatment for chronic hepatitis C patients.

BACKGROUND/AIMS: To evaluate the efficacy and tolerance of amantadine in combination with interferon in the treatment of chronic hepatitis C. METHODS: Multi-centre trial including 180 chronic hepatitis C patients without cirrhosis, randomly enrolled to receive interferon 6 MU every other day for 6 months followed by 3 MU for further 6 months (group A, 90 patients), or the same schedule plus amantadine 200 mg/day (group B, 90 patients). Primary end-point was a sustained virological and biochemical response, secondary end-points were on-treatment (third month) and end-of-treatment response rates. RESULTS: The two groups had similar demographic, biochemical and virological characteristics. A sustained response after 6 months follow-up was observed in 17% of group A and 24% of group B patients (P not significant), an end-of-treatment response was observed in 37% in group A and 47% in group B (P not significant), an on-treatment response was observed in 46% in group A and 61% in group B patients (P < 0.05). No major side effects due to amantadine administration were observed. CONCLUSIONS: Adding amantadine to interferon did not improve the sustained treatment efficacy. However, the rate of early response at the third month of therapy was significantly higher in the combination therapy group.

Adult↗

Prostate cancer screening: the problem of overdiagnosis and lessons to be learned from breast cancer screening.

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.

Aged↗

Felbamate in refractory partial epilepsy.

This open-label study was performed to evaluate efficacy and safety of Felbamate (FBM) add-on therapy in drug-refractory partial epilepsy. We evaluated 36 patients (12 males) aged 11-68 years (mean 29.8) in which FBM was titrated gradually from 300 mg/day to a mean total maintenance daily dose of 1936 mg. Patients were monitored according to clinical practice and performed regularly laboratory tests. Mean follow-up of FBM therapy was 10 months (range 2-27). In this study, 5% of patients resulted to be seizure-free, 11% showed a seizure reduction more than 75%, 23% decreased their seizure frequency between 50% and 75% (P = 0.0001). The adverse events which were reported more frequently were: nausea, vomiting, anorexia and weight loss. Even if the patients sample is small FBM proves its efficacy in partial epilepsy, showing a relatively well tolerated profile.

Adolescent↗

Overdiagnosis of prostate carcinoma by screening: an estimate based on the results of the Florence Screening Pilot Study.

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.

Aged↗

Risk of breast cancer subsequent to histological or clinical diagnosis of fibroadenoma--retrospective longitudinal study of 3938 cases.

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.

Adult↗

Pre-treatment levels of anti-HCV core IgM antibodies are closely associated with response to alpha interferon therapy in chronic hepatitis C patients.

OBJECTIVES: To investigate the relationship between pre-treatment levels of anti-hepatitis C virus (HCV) immunoglobulin M (IgM) antibodies and the outcome of interferon therapy, and also the relationship with genotypes and quantitative viraemia. PATIENTS: One hundred and four patients with biopsy-proven chronic hepatitis C without cirrhosis, consecutively enrolled in three general hospitals in Turin, Italy, and treated according to the same interferon schedule (3 MU of recombinant alpha-2b interferon three times a week for 6 months). Anti-HCV IgM were measured by a second-generation enzyme-linked immunoassay and results expressed as sample-cutoff ratio. In 30 patients, determination of viraemia by branched DNA (bDNA) and genotyping were performed and the correlation with anti-HCV IgM ratios was assessed. RESULTS: According to univariate analysis, anti-HCV IgM ratios, age, serum gamma-glutamyltranspeptidase (gamma-GT) and ferritin levels were significantly associated with sustained response to therapy. A log-linear model, testing the effect of these variables on response to therapy, showed that anti-HCV IgM ratio was the only independently associated variable (P=0.00057). Anti-HCV IgM were associated with viraemia levels (r=0.57), but not with genotype distribution. Patients with anti-HCV IgM ratio less than 1 were sustained responders to the 'standard therapy' in 65% of cases. By contrast, among patients with a ratio greater than 3, sustained response was achieved in only one patient (3%), while 73% were non-responders; the majority of relapsers were found among patients with a ratio between 1 and 3. CONCLUSION: Anti-HCV IgM antibodies provide an easily accessible and cheap serological marker of active viral replication, and are significantly related to the outcome of interferon therapy in patients with chronic hepatitis C.

Adult↗

[The hepatitis C virus].

Since 1989, when Choo and coworkers identified a new virus, i.e. virus C, as the responsible for most cases of hepatitis non-A, non-B, an impressive number of articles upon the biology, epidemiology and physiopathology of this virus has been published. The aim of this review is to summarize the most important and recent progress on C hepatitis virus such as the genotype heterogeneity, phenotype-genotype correlations, infection diffusion and pathology. Moreover, the clinical history of the illness, diagnostic methods, correlation between different clinical syndromes, such as autoimmune disorders, porphyria, cryoglobulinemia and finally the therapeutic strategies based on interferon supply, are pointed out.

Hepacivirus↗

Screening by ultrasonography for endometrial carcinoma in postmenopausal breast cancer patients under adjuvant tamoxifen.

Seven-hundred thirty-seven asymptomatic postmenopausal breast cancer patients under long-term adjuvant tamoxifen therapy (average, 50 months) were screened by endometrial ultrasonography. Abnormal endometrial thickness (6 mm or larger) was observed in 209 subjects and was significantly associated with patients' age and duration of tamoxifen therapy. Outpatient endometrial biopsy was recommended in presence of abnormal endometrial thickness: 25 subjects refused biopsy, whereas 76 were not biopsied because of cervical stenosis and were followed-up by repeat sonography. Of 108 biopsied subjects, one case of endometrial carcinoma (as expected in the screened cohort according to age-specific incidence rates provided by the regional cancer registry) and one case of endometrial hyperplasia were histologically confirmed, whereas endometrial atrophy was evident in the remaining cases. No other case of endometrial carcinoma has been recorded so far in the studied cohort according to the local cancer registry and no further change of the endometrium has been observed at sonographic follow-up. The cohort will be followed-up by repeat annual endometrial sonography. Thus far, we did not find evidence of increased prevalence of endometrial pathology (carcinoma or hyperplasia) which may be ascribed to tamoxifen therapy. The apparent increase in endometrial thickness observed at sonography might be explained by tamoxifen-induced changes of endometrial stroma and myometrium, misinterpreted as hyperplasia, while causing no real epithelial disease.

Aging↗

Trends in cervical cancer incidence in the district of Florence.

The trend in cervical cancer incidence in the District of Florence from 1975 to 1989 was investigated. Tuscany Cancer Registry data were available since 1985. Incidence data from 1975 to 1985 were obtained through a retrospective survey of all the Departments of Pathology and Gynaecology in the district. Cytological screening for cervical cancer has been available in the district since 1973, and since 1980 active invitation of residents aged 25 to 59 years has been in use. A significant trend in decreasing incidence was evident for the overall population (P = 0.003) and for 40-49 (P = 0.028), 50-59 (P < 0.001) and 60-69 (P = 0.002) year age groups, whereas no significant trend was observed for the age group 30-39 years. An association between attendance to screening and reduced incidence was evident, in that a greater reduction was evident for those cohorts (ages 50-59 and 60-69) who had a higher compliance to screening 10-15 years before. If the decrease in cervical cancer incidence was spontaneous, a parallel decrease of CIN3, which is commonly assumed to be the precursor of invasive carcinoma, would be expected. On the contrary, the detection rate of CIN3 at first Pap test showed a significant increase in the study period. All these findings suggest that the observed reduction in cervical cancer incidence was mostly due to the effect of screening, and stress the need for optimising the coverage of the invited population.

Adult↗