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Biomedical subjects

S Cecchini

Publications and source records attributed to S Cecchini.

At least 19 recordsLinked to original sources

MRI roadmap-guided transendocardial delivery of exon-skipping recombinant adeno-associated virus restores dystrophin expression in a canine model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) cardiomyopathy patients currently have no therapeutic options. We evaluated catheter-based transendocardial delivery of a recombinant adeno-associated virus (rAAV) expressing a small nuclear U7 RNA (U7smOPT) complementary to specific cis-acting splicing signals. Eliminating specific exons restores the open reading frame resulting in translation of truncated dystrophin protein. To test this approach in a clinically relevant DMD model, golden retriever muscular dystrophy (GRMD) dogs received serotype 6 rAAV-U7smOPT via the intracoronary or transendocardial route. Transendocardial injections were administered with an injection-tipped catheter and fluoroscopic guidance using X-ray fused with magnetic resonance imaging (XFM) roadmaps. Three months after treatment, tissues were analyzed for DNA, RNA, dystrophin protein, and histology. Whereas intracoronary delivery did not result in effective transduction, transendocardial injections, XFM guidance, enabled 30&#xb1;10 non-overlapping injections per animal. Vector DNA was detectable in all samples tested and ranged from <1 to >3000 vector genome copies per cell. RNA analysis, western blot analysis, and immunohistology demonstrated extensive expression of skipped RNA and dystrophin protein in the treated myocardium. Left ventricular function remained unchanged over a 3-month follow-up. These results demonstrated that effective transendocardial delivery of rAAV-U7smOPT was achieved using XFM. This approach restores an open reading frame for dystrophin in affected dogs and has potential clinical utility.

Animals

Quality control for colposcopy in the Florence screening program for cervical cancer.

The authors report on the quality control for colposcopy adopted in the Florence District screening program. The sensitivity of colposcopy was determined on all cases of CIN III recorded in the local cancer registry in a four-year period. However although this showed that a centralized colposcopic clinic employing a limited number of expert operators is superior to the performance of colposcopy in private practice, such a parameter was impractical for further routine quality control since differences among operators were too small and statistically insignificant. Other parameters for quality control were chosen, namely a) the rate of colposcopically directed biopsies performed, b) the detection rate of CIN II or more severe lesions, and c) the positive predictive value of a directed biopsy for CIN II or more severe lesions. Analysis of these indicators after stratification by cytologic report allows the identification of those operators who need additional training and provides useful information for colposcopists to optimize their diagnostic and operative criteria.

Adult

Evaluation of the sensitivity of cervicography in a consecutive colposcopic series.

Cervicography was performed in 606 women referred for colposcopy. Cervigrams were blindly reviewed by two independent readers. The positivity rate at cervicography was high (operator A = 50%, B = 58.8%). The sensitivity for papillomavirus infection (HPV)/cervical intraepithelial neoplasia I (CIN I) (n = 141) was 79.4% for operator A and 80.8% for operator B. The sensitivity for CIN II or more severe lesions (n = 22) was 95.2% and 90.5% for operators A and B, respectively. The positive predictive value for HPV/CIN I or CIN II, or more severe lesions was 36.9% and 6.9% for operator A and 32.1% and 5.3% for operator B, respectively. Interobserver variability was acceptable (kappa = 0.62). Cervicography suspected 27 HPV/CIN I, 1 CIN II and 1 CIN III which showed no cytologic abnormalities. This study confirms that cervicography has a good sensitivity for cervical lesions, but it is based on a selected series, not representative of a screening condition. The combination of cervicography and cytology in screening is presently under evaluation in a prospective study of screened women.

Adult

Determinants of non-attendance to mammographic screening. Analysis of a population sample of the screening program in the District of Florence.

The characteristics associated with non-attendance to mammographic breast cancer screening were studied by interviewing a random sample (213 attenders, 121 non-attenders in the 1989 screening) of residents in one of the municipalities of the Florence District Program, where screening has been ongoing since 1970. The overall attendance rate was 60%, and it was dependent on age (40-49 years, 66.5%; 50-59 years, 62.5%; 60-70 years, 55.5%), whereas a significant association with socio-economic status, educational level and health-behavior reported in other programs was not confirmed in the study. This finding suggests that determinants of non-attendance may vary and should be evaluated in each local setting. The belief that screening is useless, fear of cancer being detected, postponement and laziness were the most common motivations of refusal stated by non-attenders, and such a negative attitude towards screening was rather strong since most non-attenders stated they would not like to be informed or stimulated to attend future screenings. Rapid improvement of attendance rates in such a context might be achieved only by putting special pressure on women aimed to change their negative attitude towards screening and their opinion about the benefits of early breast cancer detection. This might be regarded as unacceptable and however would involve high costs and a major organization effort.

Age Factors

Loop electrosurgical excision procedure of the transformation zone and colposcopically directed punch biopsy in the diagnosis of cervical lesions.

OBJECTIVE: To estimate the disagreement between the histologic reports at colposcopically directed punch biopsy of the cervix and subsequent loop excision of the transformation zone, and to assess the indications for loop excision in current practice. METHODS: The histologic diagnoses from loop electrosurgical excision procedures and concurrent colposcopically directed punch biopsies were compared in 337 consecutive women undergoing loop excision in a 5-year period. RESULTS: Disagreement between punch biopsy and loop excision was recorded in 190 cases (56.4%). The undercall and overcall rates for punch biopsy were 14 and 42.4%, respectively. Undercall at punch biopsy occurred in 24 of 46 cases of cervical intraepithelial neoplasia (CIN) III and in one microinvasive cancer diagnosed at loop excision, and disagreement was within one grade of CIN in 16 cases. CONCLUSIONS: Loop electrosurgical excision allows further and more accurate histologic examination of the transformation zone and should be the standard assessment procedure in all cases of CIN II detected at punch biopsy and whenever cytology or colposcopy suggests the risk of punch biopsy undercall. Immediate treatment by local destruction should not be performed, to avoid underestimation of the severity of the lesion.

Biopsy

Hysteroscopy and endometrial cancer diagnosis: a review of 2007 consecutive examinations in self-referred patients.

The authors reviewed 2007 consecutive outpatient hysteroscopies performed in self-referred women to assess the detection rate of uterine cancer and the validity of different selection criteria for hysteroscopy. Thirty cases of uterine cancer (29 endometrial, 1 carcinosarcoma) were detected. Abnormal uterine bleeding was the indication most commonly associated with cancer (26 of 30 cases, cancer detection rate = 2.1%), whereas the presence of cervical polyps had no predictive value. Patients age was correlated to cancer detection rate, and the investigation of uterine cancer under the age of 45 was poorly cost effective. Hysteroscopy and endometrial biopsy, performed by Permacurette or Novak curette immediately after hysteroscopy, missed respectively 8 and 2 of 30 cancers. Hysteroscopy should be employed in combination with endometrial biopsy as a standard outpatient investigation whenever endometrial cancer is suspected. These procedures are safe and accurate and rule out more aggressive and costly procedures, such as dilatation and curettage, in most cases.

Adolescent

Attendance to a screening program for cervical cancer in the city of Florence.

The study was aimed to assess: a) the proportion of true refusers among non-attenders resulting from residents and screening database matching, b) the typology of refusers compared to attenders, and c) the reasons for non-attendance as stated by refusers. Three hundred and forty-one non-attenders according to computer-produced lists were interviewed: 29 were not evaluable, 148 had had a Pap test, 18 had not attended for valid reasons, and 146 were true refusers; 94 refusers accepted the interview as far a points b) and c) were concerned. Ninety-four attenders, matched by age and residence, were interviewed for comparison. Attendance at private laboratories or incorrect identification of subjects on the screening record accounted for 45% or 55% of misclassified cases, respectively. The adjusted true refusal rate in the last 10 years was 18.1% compared to a computer-assessed non-attendance rate of 40.7%. Refusal was significantly associated to socioeconomic status (geographic origin, working activity and educational level of both women and husbands), whereas no significant association was observed for sexual history (deliveries, age at first sexual relation, number of partners) or health-related behavior. Attendance and counseling at the gynecologist's office were strongly associated to attendance, and gynecologists should be stimulated to promote opportunistic screening. The belief that screening is useless in the absence of symptoms, the fear of cancer being detected, postponement or laziness were the reasons for non-attendance stated by 80% of refusers. Improving knowledge about the purpose of the Pap test should be the main goal of any action aimed to improve screening attendance.

Adult

Subclinical vulvar papillomavirus infection.

Eighty-eight cases of subclinical human papillomavirus (HPV) vulvar infection were detected in a consecutive colposcopic series of 968 women. Three patterns of acetowhite lesions had a 72% predictive value (88/122) for histologically assessed HPV. The prevalence of subclinical vulvar HPV in self-referred patients was 7.9% (73/918); it was 9% (88/968) in the overall series and significantly higher in younger patients (age less than 25 years: 21/106, or 19.8%) or in those with cervical HPV or cervical intraepithelial neoplasia (CIN) (40/100, or 40%). Routine inspection of the vulva after acetic acid lavage in association with a Papanicolaou test might help identify Papanicolaou-test-negative patients at high risk of developing cervical HPV or CIN. Treatment with beta-interferon (2,000,000 IU daily intramuscularly for 10 days) was given to 30 consecutive patients, but the results were poor: regression was observed in only 2 cases.

Adolescent

Early indicators of efficacy of breast cancer screening programmes. Results of the Florence District Programme.

A mammographic breast cancer screening programme has been ongoing in the Florence District (Italy) since 1970 and a favourable impact of screening on breast cancer mortality of women aged 50-70 has been shown by means of a case-control study. Two hundred and eleven screen- and 116 interval-detected cancers in the period 1975-1986 have been identified, and detection rates calculated, for first and repeated screening test (2nd to 7th). Overall, 22,980 subjects were screened and 44,988 repeated tests performed. The observed number of interval cancers has been compared with the expected incident cancers and their ratio (O/E) studied at different time intervals since last test. The O/E ratio at the third year since the last test was 0.98 for the age-group 40-49 0.50 (95% CI: 0.23-0.95) and 0.39 (95% CI: 0.26-0.94) for the 50-59 and 60-69 groups, respectively. The prevalence/incidence ratio (P/I) was then calculated as an early indicator of efficacy. For the 40-49 age-group the P/I ratio at first test was 1.09, suggesting poor anticipation of diagnosis. In contrast, for women 50-59 and 60-69 results suggest quite a good diagnosis anticipation (P/I: 3.14; 4.82), confirming the result of the previous case-control study on mortality reduction. The proportion of advanced carcinomas (stage II or worse) and 5-year survival have been analysed and discussed. The study confirms the opportunity of using early indicators of screening efficacy for monitoring of screening services.

Age Factors

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

Referral policy and positive predictive value of call for surgical biopsy in the Florence Breast Cancer Screening Program.

The authors evaluate the referral rates and the predictive value (PV) of call for diagnostic work up or biopsy in a population based breast cancer screening program in the 1979-1986 period. The presence of mammographic abnormalities either benign or suspicious proved to be the only reliable referral criterion (recall rate = 7.9%, recall PV = 3.8%, biopsy call PV = 39%). When mammography was normal the presence of breast complaints other than pain or of a radiologically dense breast were aspecific referral criteria, and since the latter was abandoned, (a) referral rates dropped especially in younger women, (b) referral or biopsy PV improved, whereas (c) cancer detection rate was almost unaffected. Younger age was associated with higher referral rates and with lower PV of both referral or biopsy. Whenever comparison with previous examination was possible, mammography accuracy was higher; this explains the decrease in referral rates and the increased predictivity observed at further rounds with respect to first screening round.

Adult

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

A centralised cytology screening programme for cervical cancer in Florence.

STUDY OBJECTIVE: The aim of the study was to evaluate the effectiveness of a centralised population based cervical cytology screening programme. DESIGN: The study was a case-control investigation. SETTING: Cases and controls were confined to the province of Florence. PARTICIPANTS: 191 out of 208 cases of cervical cancer in women less than 75 years old at diagnosis in the period 1982-85 were interviewed. For each case three living controls were selected, strictly matched by year of birth and district of residence; in all 573 controls were eventually identified. Of these, 15 had had a hysterectomy (2.6%) and were excluded, and a further 18 (3.2%) did not take part for other reasons, leaving a total of 540 controls. MEASUREMENT AND RESULTS: Screening history was taken from a computerised archive for both cases and controls. A mail questionnaire was used to collect information on several potential confounding variables. For women screened only once in comparison with those never screened, the reduction in risk was about 70% (odds ratio 0.29. 95% confidence limits 0.15-0.55), while the reduction was even greater for those screened twice or more. No trend of increasing risk with increasing interval since last test was shown: considering separately women who had only had one test and those who had had two or more tests, the risk estimates were stable across different time intervals since the last test. CONCLUSIONS: There is a strong protective effect against developing invasive cervical cancer through participation in the screening programme.

Adult

Prognosis of nonpalpable infiltrating carcinoma of the breast.

A consecutive series of 185 instances of histologically confirmed nonpalpable infiltrating carcinoma of the breast is presented. Histologic nodal involvement was found in 12 per cent and was dependent on the size of the tumor. Conservative surgical treatment was the predominant method used during the study period. The ten year over-all survival was studied and compared with that of 4,217 instances of palpable carcinoma of the breast observed during the same period. The ten year survival rates were, by far, better for nonpalpable (94 per cent) than for palpable carcinomas (65 per cent). A better prognosis for nonpalpable carcinomas was confirmed also by multivariate analysis (Cox) with adjustment for potential confounders, such as age, stage or nodal involvement. The possible confounding effect of over diagnosis and length or lead time bias is discussed. Although this difference in survival might be partially explained by the aforementioned confounders, the chance of increasing life expectancy and conservative surgical treatment encourages preclinical detection of carcinoma of the breast.

Adult

Tumor size and prognosis of breast cancer with negative axillary nodes.

A report on 1877 consecutive node negative (N-) breast cancer cases is presented in which the prognostic value of the main clinico-pathologic features is evaluated. Tumor size (and UICC-TNM T category) and lobular infiltrating histologic type were significantly associated with a more favorable prognosis whereas no association was found for patient age, tumor site and number of examined axillary nodes. However tumor size (and T category) is not a very accurate prognostic predictor (71% of all recurrences observed occurred in cases with tumor diameter of more than 20 mm, which represented 58% of the total series), although its efficiency seems almost as good as that of other more recent prognostic predictors such as estrogen receptor content or labeling index. None of the prognostic predictors currently available, including tumor size, seems sufficiently specific and they do not allow for a reliable selection of high risk N-patients for adjuvant treatment.

Adult

Mammographic parenchymal patterns and breast cancer risk. A case control study of a population-based screening experience.

The authors investigated the association between mammographic parenchymal patterns and breast cancer risk by a case control study. Three-hundred and thirty-four cancers, either screen or interval detected in the course of a screening program, were assumed as cases and compared to 668 non-cancer controls matched by age, residence and date of screening examination. Parenchymal patterns were classified by retrospective blind review of randomly mixed films by two independent readers. A high agreement was achieved on a two-group scale (N1-P1 vs P2-DY) inter and intraobserver consistency being 0.94 and 0.95, respectively. The relative risk of breast cancer exposure (RR) with respect to N1 pattern was 1.99 for P1, 3.59 for P2 and 4.18 for DY patterns. The RR of P2-DY with respect to N1-P1 patterns was 2.62. The results did not change after stratification by age group. Parenchymal patterns do not seem to be a reliable criterion for selecting high risk women for screening as in this series only 57% of all cancers occurred in high risk (P2-DY) subjects.

Age Factors

An attempt to increase compliance to cervical cancer screening through general practitioners.

The authors report the results of a campaign aimed at increasing compliance to cervical cancer screening by promoting general practitioners' (GPs) cooperation. Different types of intervention were tested, namely mailing lists of non responders to the GP, visiting the GP at the office, or both. No active intervention was made in a sample of GPs who served as a control group. Overall 288 GPs assisting 75,853 women aged 25 to 59 were enrolled in the study. Compliance before and after the campaign was studied and the association between compliance and different variables such as age, residence and type of intervention was tested by univariate and multivariate analysis. The proportion of previous non responders who performed a Pap test after the campaign was 6.7%, the response being dependent on age (25-29 = 11.5%, 30-39 = 8.8%, 40-49 = 6.5%, 50-59 = 4.2%) and place of residence (urban = 7.2%, suburban = 5.9%, rural = 4.0%). Compliance was better in the case of the active campaign (list mailing = 8.3%, visit = 7.0%, list + visit = 7.2%) with respect to controls (2.9%) although no significant differences were detected between different types of active intervention. Compliance to cervical cancer screening may be increased by promoting GPs cooperation but the benefit is limited. Mailing lists of non responders was found the most cost effective policy in this study.

Adult