Achieving the learning curve in total thyroidectomy: a prospective evaluation on resident's training by CUSUM and KPSS analysis.

INTRODUCTION: Total thyroidectomy (TT) is one of the most common procedures among general and endocrine surgeons worldwide. The conventional approach by neck incision is still the most frequently used, despite the growth of mini-invasive approaches. Controversies exist about the optimal learning curve for resident surgeons approaching this procedure. The aim of this study was to compare TT performed by experienced surgeons and residents in two academic hospitals, to define the correct shape of the specific learning curve. METHODS: Between January 2016 and December 2018 patients undergoing TT in two academic departments were prospectively enrolled. In each department patients were divided into four groups: a reference group (A), consisting of 50 consecutive patients operated on by a senior surgeon, and three other groups (B, C, D) of 50 patients each where thyroidectomy was carried out by three different general surgery residents in their last 3 years of residency, respectively. Data were analysed by CUSUM and KPSS tests in order to compare operative time (OT) and its stabilisation during the learning curve. RESULTS: Data from CUSUM test reported that residents could perform TT with OT similar to the senior surgeon after approximately 25-30 procedures, while the KPSS test showed that residents became more stable after 30 procedures, with no increase in perioperative complications. CONCLUSIONS: This prospective study shows how a specific training in thyroid surgery can be reliable thanks to experienced tutors, and confirmed that the effect of dedicated and programmed training may result in positive outcomes for patients requiring thyroidectomy.

Effectiveness of HPV vaccination in women reaching screening age in Italy.

BACKGROUND AND OBJECTIVES: A randomized trial was conducted in Tuscany, Italy, to evaluate the effectiveness of HPV vaccination for 25year old (yo) women who attend at the first time cervical cancer screening. The trial also evaluated immune response after vaccination, reductions of cytological abnormalities and the impact of vaccination on screening activity. STUDY DESIGN: During 2010-2011, all 25 yo women who were invited to the Florence cervical cancer screening programme were also asked to participate in the trial. Enrolled women were randomized into study and control groups. Those in the study group were offered HPV vaccination after the usual Pap test. The cytology distribution and prevalence for any high risk (hr) HPV type were compared at the subsequent screening round in an intention-to-treat analysis. The impact of HPV vaccination was evaluated per protocol comparing vaccinated women with the control group. RESULTS: Our results showed a reduction in HPV prevalence at recall for any hr-HPV type but it was not statistically significant, being 17.1% vs 21.4%, p=0.20 in the study and control groups, respectively. If we restricted the analysis to vaccinated women, strong reductions of the HPV 16,18,31,33,45 and HPV 31,33,45 infections were observed, being 5.3% vs 12.8%, p<0.01 and 2.1% vs 6.5%, p=0.02, respectively. Significant reductions for any hr-HPV infection and for HPV 16 infection were also observed in women HPV 16/18 negative at enrolment, being 12% vs 21.4%, p<0.01 and 0.6% vs 6.7%, p-value<0.01, respectively. In women hr-HPV negative at enrolment no infections due to HPV 16 or HPV 18 were observed and there was a big reduction for any hr-HPV infection (7.1% vs 21.4% p<0.01). A strong antibody response was observed not only for HPV 16 & 18 but also for their related types. CONCLUSIONS: Our findings suggest that HPV vaccination at the age 25 is beneficial if it is offered to hr-HPV negative women. Our data will assist in developing a cost effectiveness model for choosing the best strategy to integrate screening and vaccination for the coming years. Clinical trial registration number is NCT02296255.

hr-HPV testing in the follow-up of women with cytological abnormalities and negative colposcopy.

BACKGROUND: The follow-up after abnormal Pap smear and negative colposcopy is not clearly defined. This study aimed at investigating the role of hr-HPV testing in the management of abnormal Pap test and negative colposcopy for Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2+). methods: The study enrolled 1029 women with abnormal screening cytology (years 2006-2010) and negative colposcopy for CIN2+, which subsequently performed a hr-HPV test. Incident CIN2+ lesions were identified through linkage with cancer registry, hospital discharge records, neoplastic pathology reports and the archive of screening programme (2006-2011). RESULTS: During the follow-up, the cohort developed 133 CIN2+ lesions; only one among hr-HPV-negative women. The probability of developing CIN2+ on follow-up time was 0.44% (95% confidence interval (CI) 0.1-3.1) and 41.8% (95% CI 31.8-53.5) for hr-HPV-negative women and hr-HPV-positive women, respectively. A woman with a positive hr-HPV test had about 105 times higher probability of developing a CIN2+ lesion than a woman with a negative hr-HPV test (hazard ratio (HR)=104.5, 95% CI 14.5-755.1), adjusted for index Pap test result, age and cervix squamocolumnar junction visualisation. CONCLUSION: Our results confirm that hr-HPV testing is able to select the real group of women at risk of developing CIN2+ lesions in the follow-up of abnormal cytology and first negative colposcopy.

The effect of self-sampled HPV testing on participation to cervical cancer screening in Italy: a randomised controlled trial (ISRCTN96071600).

BACKGROUND: In Italy, cervical cancer screening programmes actively invite women aged 25-64 years. Programmes are hindered by low participation. METHODS: A sample of non-responder women aged 35-64 years, belonging to three different programmes (in Rome, Florence and Teramo), was randomly split into four arms: two control groups received standard recall letters to perform either Pap-test (first group) or human papillomavirus (HPV) test (second group) at the clinic. A third arm was sent letters offering a self-sampler for HPV testing, to be requested by phone, whereas a fourth group was directly sent the self-samplers home. RESULTS: Compliance with standard recall was 13.9% (N619). Offering HPV test at the clinic had a nonsignificant effect on compliance (N616, relative risk (RR)=1.08; 95% CI=0.82-1.41). Self-sampler at request had the poorest performance, 8.7% (N622, RR=0.62; 95% CI=0.45-0.86), whereas direct mailing of the self-sampler registered the highest compliance: 19.6% (N616, RR=1.41; 95% CI=1.10-1.82). This effect on compliance was observed only in urban areas, Florence and Rome (N438, RR=1.69; 95% CI=1.24-2.30), but not in Abruzzo (N178, RR=0.95; 95% CI=0.61-1.50), a prevalently rural area. CONCLUSIONS: Mailing self-samplers to non-responders may increase compliance as compared with delivering standard recall letters. Nevertheless, effectiveness is context specific and the strategy costs should be carefully considered.

Do women >or=50 years of age need as much screening as women <50 years after they have had negative screening results?

To assess the adequacy of a routine screening to identify cervical intraepithelial neoplasia 2 or worse (CIN2+) in women over 50 years of age, a retrospective cohort was set in six Italian organised population-based screening programmes. In all, 287 330 women (1 714 550 person-years of observation, 1110 cases) screened at age 25-64, with at least two cytological screening tests, the first negative, were followed from their first negative smear until a biopsy proven CIN2+ lesion or their last negative smear. For women aged 25-49 and 50-64 years, crude and age-standardised detection rate (DR), cumulative risk (CR), adjusted hazard risk for number of previous negative screens, probability of false-positive CIN2+ after two or more smear tests were calculated. Detection rate is significantly lower over 50 years of age. Multivariable analysis shows a significant protective effect from four screening episodes (DR=0.70, 95% CI: 0.51-0.97); the effect of age >or=50 is 0.29 (95% CI: 0.24-0.35). The CR of CIN2+ is at least eightfold higher in women <50 (CR=2.06, 95% CI: 1.88-2.23) after one previous negative test than in women >or=50 years with four screens (CR=0.23, 95% CI: 0.00-0.46). Over 50 years of age, after four tests at least three false-positive cases are diagnosed for every true positive. Benefits arising from cytological screening is uncertain in well-screened older women.

Lower protection of cytological screening for adenocarcinomas and shorter protection for younger women: the results of a case-control study in Florence.

The efficacy of cytological screening in preventing adenocarcinoma of cervix uteri as compared to squamous cell cancer has been evaluated by means of a case-control study in the province of Florence. The odds ratios of women who had a Pap test within the 3 years before the index date was 0.65 (95% confidence interval (CI) 0.26-1.64) and 0.15 (95% CI 0.07-0.31), for adenocarcinoma and squamous cancer, respectively. The duration of the protective effect was shorter in women below the age of 40 years than in older women.

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.

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.

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.

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.

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.

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.

Screening history of incident cases of invasive carcinoma of the cervix. Florence district 1988-1989.

BACKGROUND: Incidence cases of carcinoma of the cervix may be assumed as failures of a population-based cytologic screening program. Monitoring such cases would provide an estimate of screening effectiveness, and evaluating the causes of the failures would improve screening performance. STUDY DESIGN: All incident cases of cervicocarcinoma registered in 1988 and 1989 in the Tuscany Tumor Registry were eligible for the study and were reviewed. RESULTS: Sixty-nine eligible cases were considered. Non- or irregular attendance (negative smear-to-diagnosis interval > 5 years) for the Pap smear was recorded in 53 subjects. A false-negative smear (smear-to-diagnosis interval < 5 years) and refused or inadequate assessment/treatment at private practices or local hospitals were recorded in 12 cases. False-negative smears by the local screening program were recorded in 4 cases only. CONCLUSIONS: Non- or irregular attendance was the major cause of screening failures. Since cytologic screening or diagnostic assessment outside the screening program may be inadequate, central screening and follow-up is recommended. Non-attenders showed a strong negative attitude towards screening, and general practitioners and gynecologists need to be further stimulated for systematic screening promotion. Immediate evaluation of the screening history of incident cases of cervicocarcinoma should be mandatory in any screening program.

Testing cervicography and cervicoscopy as screening tests for cervical cancer.

AIMS AND BACKGROUND: Suboptimal sensitivity is currently reported for Pap test in screening for cervical cancer. Colposcopy is known to be more sensitive than cytology but its use as a screening test is not possible due to costs and complexity. Screening by cervicography has been suggested as a compromise being less costly and feasible. The present study evaluates the feasibility of screening by cervicography and cervicoscopy (naked eye examination of the cervix after acetic acid lavage) on a consecutive screening series. METHODS: Cervicography and cervicoscopy were performed by the smear taker in subjects consecutively attending a screening clinic. Women with abnormal cytology (atypia or more severe lesion) and/or abnormal cervicography or cervicoscopy (acetowhite lesion) underwent colposcopic assessment. The three screening methods were compared according to positivity rate, CIN 2-3 detection rate and positive predictive value. RESULTS: 2105 consecutive subjects were screened. Positivity rate was 3.8%, 15.3% or 25.4% for cytology, cervicography or cervicoscopy, respectively, 486 of 555 women attended the assessment phase, 281 directed biopsies were performed and 8 CIN 2-3 lesions were detected. Cytology, cervicography and cervicoscopy, detected 5.5, or 7 of 8 CIN 2-3 lesions, respectively. The positive predictive value was 0% for cytologic atypia, 25% for cytologic SIL, 1.75% for cervicography and 2.05% for cervicoscopy. Detecting one CIN 2-3 lesion at cytology cost $5,543. The cost per each additional cytologically negative CIN 2-3 lesion detected at cervicography or cervicoscopy was $12,947 or $3,916, respectively. CONCLUSIONS: The study confirms the limited sensitivity of cytology for CIN 2-3. The association of cervicography was not cost effective. Cervicoscopy was poorly specific but increased the detection rate of CIN 2-3 at relatively low costs. Cervicoscopy is worth further evaluation as a screening test.

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.