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This article discusses the role of national competition authorities in the digital sector in the lights of new legislative initiatives in Europe. It argues that the availability of multiple tools offers new opportunities to balance objectives such as flexibility, harmonization, timeliness and legal certainty, helping to enhance effectiveness. Further, it discusses the recent enforcement experience of the Autorità Garante della Concorrenza e del Mercato (AGCM), which has the dual mandate to enforce competition and consumer protection rules in Italy. The AGCM has used antitrust tools to empower consumers with choice, through a number of landmark digital cases on issues related to access and visibility in online marketplaces, refusal to deal and interoperability, data value and portability, privacy and advertising, and unfair negotiations. The AGCM has used consumer protection tools to guide consumers in the selection process, concluding numerous digital investigations on online architecture, misleading information, dark patterns and choice pressure. [ABSTRACT FROM AUTHOR]

Objectives: (a) To estimate the risk of recurrent cervical intraepithelial neoplasia, grade 2/3 or worse (CIN2+/CIN3+), lesions within 5 years of follow-up in human papillomavirus-negative/human papillomavirus-positive cohorts; (b) to assess whether certain risk factors can predict the recurrence of CIN2+/CIN3+ lesions; and (c) to provide recommendations for follow-up after treatment of cervical intraepithelial neoplasia, grade 2/3 to prevent cervical cancer. Setting: Organized cervical cancer screening programme in Central Italy. Methods: We included 1063 consecutive first excisional treatments performed between 2006 and 2014 for screening-detected cervical intraepithelial neoplasia, grade 2/3 lesions among women aged 25–65. The study population was divided into two groups according to the human papillomavirus test results performed 6 months after treatment: Human papillomavirus-negative and human papillomavirus-positive cohorts. The 5-year risk of developing cervical intraepithelial neoplasia, grade 2/3 or worse (CIN2+/CIN3+) was estimated using the Kaplan-Meier method and the Cox regression model. Results: Among 829 human papillomavirus-negative and 234 human papillomavirus-positive women, six (0.72%; three cervical intraepithelial neoplasia, grade 2, three cervical intraepithelial neoplasia, grade 3) and 45 (19.2%; 15 cervical intraepithelial neoplasia, grade 2, 30 cervical intraepithelial neoplasia, grade 3), respectively, developed CIN2+ recurrence within 5 years of follow-up. The cumulative risks for CIN2+ and CIN3+ were 0.9% (95% confidence interval: 0.4%–2.0%) and 0.5% (95% confidence interval: 0.1%–1.4%), respectively, for the human papillomavirus-negative cohort, and 24.8% (95% confidence interval: 18.5%–32.7%) and 16.9% (95% confidence interval: 11.4%–24.5%), respectively, for the human papillomavirus-positive cohort. Risk factors associated with increased risk of recurrence were both margins positive for the human papillomavirus-negative cohort, and positive margins, cervical intraepithelial neoplasia, grade 3 lesions, high-grade cytology and high viral load for the human papillomavirus-positive cohort. Conclusions: Human papillomavirus testing can identify women at increased risk of recurrence and this supports a recommendation for its use in the post-treatment follow-up of cervical intraepithelial neoplasia, grade 2/3 lesions. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between human papillomavirus vaccination status and participation in cervical cancer screening (at age 25) by the first cohorts of girls who were offered vaccination at the age of 15 to 16 years in Italy. Methods: Women born in 1993, 1994 and 1995 were invited to participate in cervical cancer screening between 2018 and 2020. We report participation in screening by vaccination status in three large areas, Florence province, Piedmont region and Savona province, where the Consensus Project was carried out. The relative risk of participation among vaccinated (≥2 doses) and unvaccinated women was estimated. Odds ratios (OR) of participation by vaccination status were estimated by logistic regression, adjusted by birthplace and birth cohort. Results: Overall, 34,993 women were invited for screening: 13,006 (37.2%) participated and 10,062 of these agreed to participate in the Consensus intervention study. Among the invited women and screening participants, vaccinated women were 51.0% and 60.6%, respectively. Comparing vaccinated and unvaccinated women, the adjusted OR of screening participation was 1.80 (95% confidence interval (CI): 1.72–1.89), 2.17 (95% CI: 1.94–2.42), 1.59 (95% CI: 1.50–1.68) and 1.15 (95% CI: 0.86–1.54) for overall, Florence, Piedmont and Savona, respectively. About 33% of the invited women were unvaccinated and did not participate in screening: 25.8%, 59.5% and 64.2% of women born in Italy, in high migration pressure countries and in advanced development countries, respectively. Conclusions: Screening participation was higher among vaccinated than unvaccinated women. Active policies are needed to reduce inequalities, targeting the unscreened and unvaccinated population, particularly non-native women, to accelerate cervical cancer elimination in Italy. [ABSTRACT FROM AUTHOR]

Purpose: This retrospective multicenter cohort study aimed to evaluate the clinical outcomes (mortality rate, operative time, complications) of elective laparoscopic cholecystectomy (LC) when performed by a surgical resident in comparison to experienced consultant in the backdrop of Italian academic centers. Methods: Retrospective review of all patients undergoing elective LC between January 2016 and January 2022 at six teaching hospitals across Italy was performed. Cases were identified using the Current Procedural Terminology (CPT) code 5123 (LC without cholangiogram). All cases of emergency surgery, ASA score > 3, or when cholecystectomy was performed with another surgical procedure, were excluded. All suitable cases were divided into 2 groups based on primary surgeon: consultant or senior resident. Main outcome was complication rates (intraoperative and peri/postoperative); secondary outcomes included operative time, the length of stay, and the rate of conversion to open. Results: A total of 2331 cases (1425 females) were included, of which, consultants performed 1683 LCs (72%), while the residents performed 648 (28%) surgeries. The groups were statistically comparable regarding demographics, history of previous abdominal surgery, operative time, or intraoperative complications. The rate of conversion to open cholecystectomy was 1.42% for consultant and none for resident (p = 0.02). A statistically significant difference was observed between groups regarding the average length of stay (2.2 ± 3 vs 1.6 ± 1.3 days p = 0.03). Similarly, postoperative complications (1.7% vs 0.5%) resulted in statistically significant (p = 0.02) favoring resident group. Conclusions: Our study demonstrates that in selected patients, senior residents can safely perform LC when supervised by senior staff surgeons. [ABSTRACT FROM AUTHOR]

Objective: To evaluate performance of the first round of HPV-based screening in Tuscany region and compare it with the prior round of Pap-based screening Setting: Tuscany region of Italy, where HPV-based cervical cancer screening started in 2013, with a strong level of centralization screening tests at the Regional Laboratory for Cancer Prevention (ISPRO). Methods: The transition from Pap- to HPV-based screening was initiated for older women and at 3 out of 12 Tuscany Local Health Units (LHUs). Data from the Florence and Grosseto LHUs (about 300,000 women) were analysed and performance screening indicators estimated. Results: HPV-based indicators recorded good performance, with increased compliance vs. the Pap-based programme. We registered a substantial decrease in waiting times from sampling to test reporting, probably related to the centralization strategy. Since the screening protocol was the same and conducted at a single laboratory, we could hypothesize that the difference in HPV positivity (6.8% in Florence vs. 8.4% in Grosseto) was due to a real difference in HPV prevalence among women of the two LHUs. The transition to HPV-based screening led to a significant increase both in colposcopy referral rate (4.3% vs. 1.2%) and CIN2+ detection rate (8.3‰ vs. 3.4‰). Conclusions: HPV-based is more effective in detecting high-grade precancerous and cancerous lesions than Pap-based screening and is characterized by an "anticipatory effect" in the detection of CIN2+ lesions. The transition from Pap-based to HPV-based screening programme should include increased resources dedicated to colposcopy services. Centralization in a laboratory with long experience in this field promotes efficiency of the screening process. [ABSTRACT FROM AUTHOR]

The article discusses the analysis of the SLC26A4 gene of 30 Italian children with severe-to-profound congenital sensorineural hearing loss (SNHL). It states the identification of 10 independent mutated alleles and another variant p.I655V that is indicated as pathogenic only in gene-specific mutation/SNP databases. It mentions that mutation of SLC26A4 is relevant cause of deafness.

Background: Mitochondria are the main cellular sites devoted to ATP production and lipid oxidation. Therefore, the mitochondrial dysfunction could be an important determinant of cellular fate of circulating lipids, that accumulate in the cytoplasm, if they are not oxidized. The ectopic fat accumulation is associated with the development of insulin resistance, and a link between mitochondrial dysfunction and insulin resistance has been proposed. Methods: Recent data on the possible link existing between mitochondrial dysfunction in the liver and diet-induced obesity will be summarized, focusing on the three factors that affect the mitochondrial oxidation of metabolic fuels, i.e. organelle number, organelle activity, and energetic efficiency of the mitochondrial machinery in synthesizing ATP. Search in PubMed relevant articles from 2003 to 2014 was conducted, by using query 'liver mitochondria and obesity' 'hepatic mitochondria and obesity' 'liver mitochondria and high fat diet' and 'hepatic mitochondria and high fat diet' and including related articles by the same groups. Results: Several works, by using different physiological approaches, have dealt with alteration in mitochondrial function in obesity and diabetes. Most results show that hepatic mitochondrial function is impaired in models of obesity and insulin resistance induced by high-fat or high-fructose feeding. Conclusions: Since mitochondria are the main producers of both cellular energy and free radicals, dysfunctional mitochondria could play an important role in the development of insulin resistance and ectopic fat storage in the liver, thus supporting the emerging idea that mitochondrial dysfunction is closely related to the development of obesity, type 2 diabetes mellitus and non-alcoholic steatohepatitis. [ABSTRACT FROM AUTHOR]

Few studies analyzed the risk for high-grade squamous intraepithelial lesions or worse (HSIL+) among immigrants and natives attending organized cervical cancer (CC) screening programs (SP). We evaluated participation and diagnosis of HSIL+ by country of birth with logistic models. Overall 540,779 invitation letters were delivered to target women of Florence SP in three screening rounds (years 2000-2002, 2003-2005, 2006-2008). The probability of attending screening was lower for immigrants than natives, but the difference decreased from 35 % (1st round) to 20 % (2nd-3rd round) for women born in high migration pressure (HMP) countries. The risk of HSIL+ was double than natives for HMP-born women from countries with high prevalence of human papillomavirus, even adjusting for age and previous history of Pap test. This is an important public health problem due to an increasing proportion over time of immigrant women with a lower attendance and greater risk for CC. [ABSTRACT FROM AUTHOR]

Purpose: To study the effect of isoenergetic administration to adult rats of high-fat or high-fat-high-fructose diet for 2 weeks on skeletal muscle mitochondrial energetic. Methods: Body and skeletal muscle composition, energy balance, plasma lipid profile and glucose tolerance were measured, together with mitochondrial functionality, oxidative stress and antioxidant defense. Results: Rats fed high-fat-high-fructose diet exhibited significantly higher plasma triglycerides and non-esterified fatty acids, together with significantly higher plasma glucose and insulin response to glucose load. Skeletal muscle triglycerides and ceramide were significantly higher in rats fed high-fat-high-fructose diet. Skeletal muscle mitochondrial energetic efficiency and uncoupling protein 3 content were significantly higher, while adenine nucleotide translocase content was significantly lower, in rats fed high-fat or high-fat-high-fructose diet. Conclusions: The results suggest that a high-fat-high-fructose diet even without hyperphagia is able to increase lipid flow to skeletal muscle and mitochondrial energetic efficiency, with two detrimental effects: (a) energy sparing that contributes to the early onset of obesity and (b) reduced oxidation of fatty acids and lipid accumulation in skeletal muscle, which could generate insulin resistance. [ABSTRACT FROM AUTHOR]

Purpose: To explore the effect of a fructose-rich diet on morphological and functional changes in white adipose tissue (WAT) that could contribute to the development of insulin resistance. Methods: Adult sedentary rats were fed a fructose-rich diet for 8 weeks. Glucose tolerance test was carried out together with measurement of plasma triglycerides, non-esterified fatty acids and lipid peroxidation. In subcutaneous abdominal and intra-abdominal WAT, number and size of adipocytes together with cellular insulin sensitivity and lipolytic activity were assessed. Results: Rats fed a fructose-rich diet exhibited a significant increase in plasma insulin, triglycerides, non-esterified fatty acids and lipid peroxidation, together with significantly increased body lipids and epididymal and mesenteric WAT, compared to controls. Mean adipocyte volume in subcutaneous abdominal WAT was significantly lower, while mean adipocyte volume in intra-abdominal WAT was significantly higher, in rats fed a fructose-rich diet compared to controls. A significant increase in larger adipocytes and a significant decrease in smaller adipocytes were found in intra-abdominal WAT in rats fed a fructose-rich diet compared to controls. Insulin's ability to inhibit lipolysis was blunted in subcutaneous abdominal and intra-abdominal adipocytes from fructose-fed rats. Accordingly, lower p-Akt/Akt ratio was found in WAT in rats fed a fructose-rich diet compared to controls. Conclusions: Long-term consumption of high levels of fructose elicits remarkable morphological and functional modifications, particularly in intra-abdominal WAT, that are highly predictive of obesity and insulin resistance and that contribute to the worsening of metabolic alterations peculiar in a fructose-rich, hypolipidic diet. [ABSTRACT FROM AUTHOR]

Abstract Objective: To determine the incidence of GJB2 and GJB3 mutations and of two deletions upstream of the GJB6 gene in infants of the Campania region of southern Italy. Design : DNA samples from non-syndromic hearing-impaired infants enrolled in a neonatal screening programme for sensorineural hearing loss were analysed by PCR and by direct sequencing. The audiological features of infants with biallelic GJB2 mutations were also examined to identify genotype-phenotype correlations. Study sample : Molecular analyses were carried out in 129 affected and five unaffected infants. Results: A genetic etiology of hearing loss was identified in 28% of infants, including several at environmental risk of hearing loss. Neither GJB6 nor GJB3 (a gene not previously investigated in the Campania population) mutations were found. Conclusions: This study confirms the importance of universal neonatal hearing screening. The identification of a genetic cause in infants at environmental risk indicates that such infants should be included when investigating etiology. We confirm that also in our geographical area, c.35delG homozygotes tend to have severe symmetrical hearing loss, whereas hearing impairment is milder in compound heterozygotes. Sumario Objetivo: Determinar la incidencia de mutaciones GJB2 y GJB3 y de dos deleciones corriente arriba en el gen GJB6 en niñosde la región de Campania en el sur de Italia. Diseño: Se analizaron por PCR y por secuenciación directa muestras de ADN de niños con trastornos auditivos no sindrómicos incluidos en el programa de tamiz neonatal para hipoacusias sensorineurales. Los rasgos audiológicos de niños con mutaciones bi-alélicas del GJB2 también se examinaron para identificar correlaciones genotípicas y fenotípicas. Muestra del Estudio: Se realizó un análisis molecular en 129 niños afectados y en 5 no afectados. Resultados: Se identificó una etiología genética de la sordera en 28% de los infantes, incluyendo varios con riesgo ambiental de hipoacusia. No se encontraron mutaciones en el gen GJB6 o en el GJB3 (un gene no investigado previamente en la población de Campania). Conclusiones: Este estudio confirma la importancia del tamiz auditivo neonatal universal. La identificación de una causa genética en niños con un riesgo ambiental indica que tales infantes deberían incluirse cuando se investiga la etiología. Confirmamos que también en nuestra área geográfica, los homocigotos c.35delG tienden a tener hipoacusias simétricas severas, mientras que el trastorno auditivo es más leve en heterocigotos compuestos. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract The aim of this study was to screen 349 patients affected by sensorineural hearing loss (SNHL), mostly from the Campania region (southern Italy), for GJB2 gene mutations and for two deletions of the GJB6 gene (del GJB6 -D13S1830 and del GJB6 -D13S1854). We identified pathogenetic GJB2 mutations in 51 cases (15% of patients). No GJB6 mutation was found. We also examined the audiologic features of the patients for whom we had an etiologic diagnosis, in order to identify correlations between the severity of hearing loss and the type of mutation. Sumario El objetivo de este estudio fue evaluar 349 pacientes afecta-dos de una hipoacusia sensorineural (SNHL), sobre todo de la región de Campania (Italia del sur), buscando muta-ciones en el gen GJB2 y dos deleciones en el gen GJB6 (del GJB6-D13S1830 y del GJB6-13S1854). Identifica-mos mutaciones patogénicas en 51 pacientes (15% de los pacientes). No se encontraron mutaciones del gen GJB6. También examinamos los rasgos audiológicos de aquellos pacientes de quienes teníamos diagnóstico etiológico, para identificar correlaciones entre la severidad de la pérdida audi-tiva y el tipo de mutación. [ABSTRACT FROM AUTHOR]

Background: There is conclusive evidence that human papillomavirus (HPV) infections of the cervix are a necessary cause of cervical cancer. In Italy there are consistent data of HPV prevalence in women aged 25 - 64 years, but there is limited data for younger women. The objective of this on-going 3-year prospective cohort study is to investigate the prevalence, acquisition, clearance and persistence of HPV infections in young Tuscan women and the risk factors correlated with such events. Methods: One thousand and sixty-six women aged between 18 and 24 years were enrolled and received an initial HPV test. They were asked to return to the clinic over the study period for further tests every 12 months, if their HPV HR result was negative, or every 6 months, if positive. Additionally, women with an HPV positive result were given a cytological examination and if the cytological diagnosis was ASC-US or more severe, only women with HPV HR, were referred for colposcopy. Results: We present here data for the enrolment phase of the study. At baseline, within the study sample, just under 30% of women were infected by HPV and 19.3% of women were infected with oncogenic types. A relationship was highlighted between HPV infection, number of sexual partners (in particularly in the last 3 years) and the lifetime number of partner's partners. Condom use showed a slight protective effect in univariate analysis but these data were not statistically significant in multivariate analysis. The association between HPV infection and demographic and behavioural variables were tested by crude odds ratio (OR). Multivariate logistic regression was applied to compute the adjusted odds ratios. Conclusions: The prevalence of oncogenic HPV types was high in young Tuscan women. The 3-year follow-up of this cohort may provide a better understanding of the processes of acquisition, clearance and persistence of infection and the correlated risk factors. [ABSTRACT FROM AUTHOR]

Background and objectives A randomized trial was conducted in Tuscany, Italy, to evaluate the effectiveness of HPV vaccination for 25 year 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. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to analyze short-term outcomes focusing on readmissions after laparoscopic bariatric metabolic surgery (BMS) in an Italian academic Bariatric Center of Excellence IFSO-European Chapter (EC)., Methods: This is a retrospective study based on the analysis of a prospectively maintained institutional database. Patients aged between 18 and 65 years who underwent primary BMS and/or revisional BMS (RBMS) between 2012 and 2021 were included. Primary endpoint was to analyze the readmission rate at 30 postoperative days. The secondary endpoint involved assessing the causes of readmission within 30 days of discharge, the rates, and types of reoperations and/or additional procedures related to the first surgery, and the outcomes of readmitted patients., Results: A total of 2297 patients were included in the study. Among them, 2143 underwent primary surgery and 154 patients underwent RBMS. Eighty-two percent of the Enhanced Recovery after Surgery (ERAS) protocol items were applied starting from 2016. Within 30 days after discharge, 48 patients (2.09%) were readmitted. Overall readmission rate following primary and revisional BMS was 2.15%, respectively 1.30%. Ten readmitted patients (20.8%) had complications graded IIIb or more (Clavien-Dindo classification) and needed additional procedures. Mortality rate was 4.17% among readmitted patients., Conclusions: Only 2.09% of patients undergoing laparoscopic bariatric surgery were readmitted. Of these, 20.8% required additional procedures. Standardization of surgical techniques and perioperative protocols in a bariatric center of excellence resulted in a low readmission rate even in RBMS.

Background: Each high-risk HPV genotype has different oncogenic potential, and the risk of CIN3+ varies according to genotype. We evaluated the performance of different strategies of HPV-positivity triage combining cytology, p16/ki67 dual staining (DS), and extended genotyping., Methods: Samples from 3180 consecutive women from the NTCC2 study (NCT01837693) positive for HPV DNA at primary screening, were retrospectively analyzed by the BD Onclarity HPV Assay, which allows extended genotyping. Genotypes were divided into three groups based on the risk of CIN3+. HPV DNA-positive women were followed up for 24 months or to clearance., Findings: Combining the three groups of genotypes with cytology or DS results we identify a group of women who need immediate colposcopy (PPV for CIN3+ from 7.8 to 20.1%), a group that can be referred to 1-year HPV retesting (PPV in those HPV-positive at retesting from 2.2 to 3.8), and a group with a very low 24-month CIN3+ risk, i.e. 0.4%, composed by women cytology or DS negative and positive for HPV 56/59/66 or 35/39/68 or negative with the Onclarity test, who can be referred to 3-year retesting., Interpretation: Among the baseline HPV DNA positive/cytology or DS negative women, the extended genotyping allows to stratify for risk of CIN3+, and to identify a group of women with a risk of CIN3+ so low in the next 24 months that they could be referred to a new screening round after 3 years., Funding: Italian Ministry of Health (grant number RF-2009-1536040). Hologic-Genprobe, Roche Diagnostics, and Becton & Dickinson provided financial and non-financial support., Competing Interests: Declaration of interests Maria Benevolo and Paolo Giorgi Rossi as principal investigator and former PI of the NTCC2 study reports nonfinancial support from Roche Diagnostics and Hologic S. r.l., which provided part of the reagents for free or at reduced price. Moreover, Maria Benevolo, Paolo Giorgi Rossi, Simonetta Bisanzi, and Laura De Marco obtained financial and nonfinancial support from Becton & Dickinson. Maria Benevolo also reports financial and nonfinancial support from Arrow S. r.l. for works outside this project. All other authors declare no conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The present paper aims at evaluating the potential benefits of high-energy devices (HEDs) in the Italian surgical practice, defining the comparative efficacy and safety profiles, as well as the potential economic and organizational advantages for hospitals and patients, with respect to standard monopolar or bipolar devices., Methods: A Health Technology Assessment was conducted in 2021 assuming the hospital perspective, comparing HEDs and standard monopolar/bipolar devices, within eleven surgical settings: appendectomy, hepatic resections, colorectal resections, cholecystectomy, splenectomy, hemorrhoidectomy, thyroidectomy, esophago-gastrectomy, breast surgery, adrenalectomy, and pancreatectomy. The nine EUnetHTA Core Model dimensions were deployed considering a multi-methods approach. Both qualitative and quantitative methods were used: (1) a systematic literature review for the definition of the comparative efficacy and safety data; (2) administration of qualitative questionnaires, completed by 23 healthcare professionals (according to 7-item Likert scale, ranging from - 3 to + 3); and (3) health-economics tools, useful for the economic evaluation of the clinical pathway and budget impact analysis, and for the definition of the organizational and accessibility advantages, in terms of time or procedures' savings., Results: The literature declared a decrease in operating time and length of stay in using HEDs in most surgical settings. While HEDs would lead to a marginal investment for the conduction of 178,619 surgeries on annual basis, their routinely implementation would generate significant organizational savings. A decrease equal to - 5.25/-9.02% of operating room time and to - 5.03/-30.73% of length of stay emerged. An advantage in accessibility to surgery could be hypothesized in a 9% of increase, due to the gaining in operatory slots. Professionals' perceptions crystallized and confirmed literature evidence, declaring a better safety and effectiveness profile. An improvement in both patients and caregivers' quality-of-life emerged., Conclusions: The results have demonstrated the strategic relevance related to HEDs introduction, their economic sustainability, and feasibility, as well as the potentialities in process improvement., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The published colorectal cancer (CRC) outcomes after bariatric surgery (BS) are conflicting, with some anecdotal studies reporting increased risks. The present nationwide survey CRIC-ABS 2020 (Colo-Rectal Cancer Incidence-After Bariatric Surgery-2020), endorsed by the Italian Society of Obesity Surgery (SICOB), aims to report its incidence in Italy after BS, comparing the two commonest laparoscopic procedures-Sleeve Gastrectomy (SG) and Roux-en-Y gastric bypass (GBP)., Methods: Two online questionnaires-first having 11 questions on SG/GBP frequency with a follow-up of 5-10 years, and the second containing 15 questions on CRC incidence and management, were administered to 53 referral bariatric, high volume centers. A standardized incidence ratio (SIR-a ratio of the observed number of cases to the expected number) with 95% confidence intervals (CI) was calculated along with CRC incidence risk computation for baseline characteristics., Results: Data for 20,571 patients from 34 (63%) centers between 2010 and 2015 were collected, of which 14,431 had SG (70%) and 6140 GBP (30%). 22 patients (0.10%, mean age = 53 ± 12 years, 13 males), SG: 12 and GBP: 10, developed CRC after 4.3 ± 2.3 years. Overall incidence was higher among males for both groups (SG: 0.15% vs 0.05%; GBP: 0.35% vs 0.09%) and the GBP cohort having slightly older patients. The right colon was most affected (n = 13) and SIR categorized/sex had fewer values < 1, except for GBP males (SIR = 1.07)., Conclusion: Low CRC incidence after BS at 10 years (0.10%), and no difference between procedures was seen, suggesting that BS does not trigger the neoplasm development., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

As the world population is aging rapidly, emergency abdominal surgery for acute abdomen in the elderly represents a global issue, both in developed and developing countries. Data regarding all the elderly patients who underwent emergency abdominal surgery from January 2017 to December 2017 at 36 Italian surgical departments were analyzed with the aim to appraise the contemporary reality regarding the use of emergency laparoscopy for acute abdomen in the elderly. 1993 patients were enrolled. 1369 (68.7%) patients were operated with an open technique; whereas, 624 (31.3%) underwent a laparoscopic operation. The postoperative morbidity rate was 32.6%, with a statically significant difference between the open and the laparoscopic groups (36.2% versus 22.1%, p < 0.001). The reported mortality rate was 8.8%, with a statistically significant difference between the open and the laparoscopic groups (11.2% versus 2.2%, p < 0.001). Our results demonstrated that patients in the ASA II (58.1%), ASA III (68.7%) and ASA IV (88.5%) groups were operated with the traditional open technique in most of the cases. Only a small percentage of patients underwent laparoscopy for perforated gastro-duodenal ulcer repair (18.9%), adhesiolyses with/without small bowel resection (12.2%), and large bowel resection (10.7%). Conversion to open technique was associated with a higher mortality rate (11.1% versus 2.2%, p < 0.001) and overall morbidity (38.9% versus 22.1%, p = 0.001) compared with patients who did not undergo conversion. High creatinine (p < 0.001) and glycaemia (p = 0.006) levels, low hemoglobin levels (p < 0.001), oral anticoagulation therapy (p = 0.001), acute respiratory failure (p < 0.001), presence of malignancy (p = 0.001), SIRS (p < 0.001) and open surgical approach (p < 0.001) were associated with an increased risk of postoperative morbidity. Regardless of technical progress, elderly patients undergoing emergency surgery are at very high risk for in-hospital complications. A detailed analysis of complications and mortality in the present study showed that almost 9% of elderly patients died after surgery for acute abdomen, and over 32% developed complications.

Cervical cancer screening by human papillomavirus (HPV) DNA testing with cytology triage is more effective than cytology testing. Compared to cytology, the HPV DNA test's higher sensitivity, which allows better protection with longer intervals, makes it necessary to triage the women with a positive result to compensate its lower specificity. We are conducting a large randomized clinical trial (New Technologies for Cervical Cancer 2 [NTCC2]) within organized population-based screening programs in Italy using HPV DNA as the primary screening test to evaluate, by the Aptima HPV assay (Hologic), the use of HPV E6-E7 mRNA in a triage test in comparison to cytology. By the end of June 2016, data were available for 35,877 of 38,535 enrolled women, 2,651 (7.4%) of whom were HPV DNA positive. Among the samples obtained, 2,453 samples were tested also by Aptima, and 1,649 (67.2%) gave a positive result. The proportion of mRNA positivity was slightly higher among samples tested for HPV DNA by the Cobas 4800 HPV assay (Roche) than by the Hybrid Capture 2 (HC2) assay (Qiagen). In our setting, the observed E6-E7 mRNA positivity rate, if used as a triage test, would bring a rate of immediate referral to colposcopy of about 4 to 5%. This value is higher than that observed with cytology triage for both immediate and delayed referrals to colposcopy. By showing only a very high sensitivity and thus allowing a longer interval for HPV DNA-positive/HPV mRNA-negative women, a triage by this test might be more efficient than by cytology., (Copyright © 2017 American Society for Microbiology.)

With the introduction of Human papillomavirus (HPV) vaccination in young girls in 2007, it is important to monitor HPV infections and epidemiological changes in this target population. The present study has evaluated the detection of human papillomavirus DNA in paired cervical and urine samples to understand if HPV testing in urine could be used as non-invasive method to monitor HPV status in young women. The study enrolled 216 twenty five-year-old women, resident in Florence and invited for the first time to the cervical cancer Screening Program within a project evaluating the impact of HPV vaccination. HPV genotyping was performed on 216 paired urine and cervical samples. The overall concordance between cervix and urine samples, investigated by HPV genotyping (INNO-LiPA HPV Genotyping Extra), was: 85.6% (184/215), 84.6% (182/215), 80% (172/215) when the same HPV, at least the same HR HPV and all HR HPV, respectively, were detected. HPV type specific concordance in paired urine and cervical samples was observed in 85.8% (175/204) of women with normal cytology and in seven out of nine women with abnormal cytology. Urine seems to be a suitable and reliable biological material for HPV DNA detection as evidenced by the high concordance with HPV detected in cervical samples. These results suggest that urine could be a good noninvasive tool to monitor HPV infection in vaccinated women., (© 2014 Wiley Periodicals, Inc.)

Italian national guidelines recommend to regions the implementation of organised screening programmes for cervical cancer. As in previous years since 1998 we collected aggregated tables of data from Italian organised cervical screening programmes in order to centrally compute process indicators. Data on women invited during 2010 and screened up to April 2011 were considered. In 2010, the target population of Italian organised screening programmes included 13,538,080 women, corresponding to 80.1% of Italian women aged 25-64 years. Compliance to invitation was 39.8%, with a strong North-South decreasing trend. However, it should be considered that many women are screened outside organised programmes. Among screened women, 4.7% were referred for repeat cytology and 62.7% of them complied; 2.5% of screened women were referred to colposcopy. Compliance with colposcopy referral was 85.9% among women referred because of ASC-US or more severe cytology and 88.7% among those referred because of HSIL or more severe cytology. The positive predictive value (PPV) of referral because of ASC-US or more severe cytology for CIN2 or more severe histology was 16.0%. The unadjusted detection rate of CIN2 or more severe histology was 3.2 per 1,000 screened women (3.5 standardised on the Italian population, truncated 25-64).

Background: The organized Cervical Cancer Screening Programme (CCSP) in Italy might represent an occasion to deliver smoking cessation (SC) counselling to women attending the Pap test examination. Evidence of effectiveness of physical activity (PA) promotion and intervention in adjunct to SC counselling is not strong.Objective of the SPRINT trial was to evaluate the effectiveness of a standard SC counselling intervention delivered by trained midwives in the CCSP, and whether the adjunct of a PA counselling to the SC counselling might increase quit rates., Methods/design: We undertook a randomized controlled trial of 1,100 women undergoing the Pap examination in the three study centres Florence, Turin, and Mantua: 363 were randomly assigned to the SC counselling arm, 366 to the SC + PA counselling arm, and 371 to the control group. The intervention was a standard brief SC counselling combined with a brief counselling on increasing PA, and was tailored according to the Di Clemente-Prochaska motivational stages of change for SC and/or PA. Primary outcomes were quit rates, improvement in the motivational stages of change for SC, and reduced daily cigarette consumption. Analysis was by intention to treat., Results: Participants randomized in both intervention arms and in the preparation stage of change for SC doubled their likelihood of quitting at 6-month follow-up in comparison to controls (odds ratio [OR]=2.1, 95% confidence interval [95% CI]:1.0-4.6). Moreover, participants in the intervention arms and in the contemplation stage were more likely to reduce their daily cigarette consumption after the intervention (OR=1.8, 95% CI:1.1-3.0). Our study did not show any effect of PA counselling on various outcomes., Conclusions: Smoking cessation counselling delivered by midwives to smokers in preparation and contemplation stages of change during the Pap-smear screening was effective and should be recommended, given the high number of women attending the cervical cancer screening programme in Italy. Moreover, the daily number of women invited for the Pap-smear examination should be slightly lowered, in order to let midwives deliver SC counselling to smokers., Trial Registration: Current Controlled Trials ISRCTN52660565.

Aims and Background: In the last decades in Italy, a smaller decrease in smoking among women than in men has been observed and a younger age at start in young women. Nevertheless, gender-specific strategies for smoking cessation have rarely been developed, except those for pregnant women. A study was conducted to evaluate the feasibility of carrying out an intervention of primary prevention by counseling for smoking cessation the female smokers attending cervical cancer screening programs in Florence, Italy., Methods: All female smokers attending the services for cervical cancer prevention at the Cancer Prevention and Research Institute in Florence, Italy, between March 2004 and January 2005, who volunteered to participate in the study, received a brief motivational stage-matched counseling for smoking cessation and a face to face interview at enrollment and after 6 and 12 months. The counseling was evaluated by comparing quit rates, changes in smoking intensity, and motivation to quit at the first and second follow-up periods to the same data collected at enrollment. Multivariate logistic regression analysis was performed to estimate the influence on smoking cessation of demographic characteristics, smoking habit and attitude to quit., Results: 177 women participated in the study. After 1 year, a quit rate of 12.4% (95% CI, 7.5-17.3) was observed. Among those who never quit, there was a 39.3% reduction in the average daily cigarette consumption and a 51.9% reduction in smoking the first cigarette of the day immediately on awaking or just after breakfast., Conclusions: The results and the opportunity to contact a large number of female smokers on the occasion of cervical cancer screening suggest the importance to evaluate the efficacy of the intervention of primary prevention in this health setting.

Italian national guidelines recommend to regions the implementation of organised screening programmes for cervical cancer. As in previous years since 1998, we collected from Italian organised cervical screening programmes aggregated tables of data in order to centrally compute process indicators. Data on women invited during 2009 and screened up to April 2010 were considered. In 2009, the target population of Italian organised screening programmes included 13,120,269 women, corresponding to 78.0%of Italian women aged 25-64 years. Compliance to invitation was 39.3%, with a strong North-South decreasing trend. However, it should be considered that many women are screened outside the organised programmes. Of the women screened, 4.7%were referred for repeat cytology and 60.8% of them complied; 2.4% of screened women were referred to colposcopy. Compliance with colposcopy referral was 85.1% among women referred because of ASC-US or more severe cytology and 89.3% among those referred because of HSIL or more severe cytology. The positive predictive value (PPV) of referral because of ASC-US or more severe cytology for CIN2 or more severe histology was 16.2%. The unadjusted detection rate of CIN2 or more severe histology was 3.2 per 1,000 screened women (3.2 standardised on the Italian population, truncated 25-64).

Italian national guidelines recommend to Regions the implementation of organised screening programmes for cervical cancer. As in previous years since 1998, we collected from Italian organised cervical screening programmes aggregated tables of data in order to centrally compute process indicators. Data on women invited during 2008 and screened up to April 2009 were considered. In 2008, the target population of Italian organised screening programmes included 13,094,025 women, corresponding to 78.4% of Italian women aged 25-64 years. Compliance to invitation was 39.7%, with a strong North-South decreasing trend. However, it should be considered that many women are screened outside the organised programmes. Of the women screened, 5.2%were referred for repeat cytology and 63.0% of them complied; 2.4% of screened women were referred to colposcopy. Compliance with colposcopy referral was 85.1%among women referred because of ASCUS or more severe cytology and 89.3%among those referred because of HSIL or more severe cytology.The positive predictive value (PPV) of referral because of ASCUS or more severe cytology for CIN2 or more severe histology was 16.0%. The unadjusted detection rate of CIN2 or more severe histology was 3.1 per 1,000 screened women (3.0 standardised on the Italian population, truncated 25-64).

Italian national guidelines recommend to Regions the implementation of organised screening programmes for cervical cancer. As in previous years since 1998, we collected from Italian organised cervical screening programmes aggregated tables of data in order to centrally compute process indicators. Data on women invited during 2007 and screened up to April 2008 were considered. In 2007, the target population of Italian organised screening programmes included 11,872,810 women, corresponding to 71.8% of Italian women aged 25-64 years. Uptake of invitation was 39.8%, with a clear North-South decreasing trend. It should, however, be considered that many women are screened outside the organised programmes. Of the women screened, 5.0% were referred for repeat cytology and 60.4 % of them complied; 2.4% of screened women were referred to colposcopy. Compliance with colposcopy referral was 82.3% among women referred because of ASCUS or more severe cytology and 89.5% among those referred because of HSIL or more severe cytology. The positive predictive value (PPV) of referral because of ASCUS or more severe cytology for CIN2 or more severe histology was 16.0%. The unadjusted detection rate of CIN2 or more severe histology was 2.9 per 1,000 screened women (3.1 standardised on the Italian population, truncated 25-64).

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.

Since 1996, Italian national guidelines recommend that Regions implement organised screening programmes for cervical cancer. As in previous years since 1998, we have collected from Italian organised cervical screening programmes aggregated tables of data in order to centrally compute process indicators. In 2006, the target population of Italian organised screening programmes included 11,362,580 women, corresponding to 69% of Italian women aged 25-64 years. However, taking into account the proportion of women invited, the actual extension was 52.9%. Compliance to invitation was 38.5%, with a clear North-South decreasing trend. It should, however, be considered that many women are screened outside the organised programmes. The remaining process indicators deal with women invited during 2005 and screened up to April 2006 Of these, 6.1% were recommended to repeat cytology and 57% of them complied; 2.3% of screened women were referred to colposcopy. Compliance to colposcopy was 84.7% among women referred because of ASCUS or more severe cytology and 90% among those referred because of HSIL or more severe cytology. The positive predictive value (PPV) of referral because of ASCUS or more severe cytology for CIN2 or more severe histology was 16.8%. There was a relevant variability of both referral rate and PPV that were inversely related. The unadjusted detection rate of histologically confirmed CIN2 or more severe was 2.7 per 1,000 screened women (2.6 standardised on the Italian population, truncated 25-64).

Since 1996, Italian national guidelines have recommended to regions the implementation of organised screening programmes for cervical cancer. As in the previous years, starting from 1998, we collected aggregated tables of data from Italian organised cervical screening programmes in order to centrally compute process indicators. In 2005, the target population of Italian organised screening programmes included 10,969,571 women, corresponding to 66.7% of Italian women aged 25-64 years. However, these programmes invited only 24.8% of their target population in 2005, vs. 33.3% expected in order to invite the entire target population in the 3-year recommended interval. Compliance to invitation was 36.7%, with a clear North-South decreasing trend. It must however be considered that many women are screened outside the organised programmes. The remaining process indicators deal with women invited during 2004 and screened up to April 2005. Unsatisfactory smears were 3.1%. It was recommended to 6.1% of women to repeat cytology, and 61% of them complied. Some (2.5%) of screened women were referred to colposcopy. Compliance to colposcopy was 84.7% among women referred because of ASCUS or more severe cytology and 88.2% among those referred because of HSIL or more severe cytology. The Positive Predictive Value (PPV) of referral because of ASCUS or more severe cytology for CIN2 or more severe histology was 15.5%. There was a relevant variability of both referral rate and PPV, that were inversely related, and 10 % ofprogrammes referred > 5% of women, suggesting too broad criteria of interpretation of cytology. The unadjusted detection rate ofhistologically confirmed CIN2 or more severe was 2.7 per 1000 screened women (3.0 per 1000, standardised on the Italian population, truncated 25-64).

The target population of Italian organised cervical screening programmes that were active (that invited at least 1000 women) in 2004 was 10,206,741 women, corresponding to 64% of the Italian female population in the 25-64 year age range. This proportion was 66%, 83% and 49% in Northern, Central, and Southern Italy respectively. Some 27% of this target population was invited during 2004. Among women invited in 2004, 37.7% had cytology within organised programmes up to April 2005 (46.2%, 36.0% and 26.2% in Northern, Central, and Southern Italy respectively). It must be kept in mind that many women have spontaneous tests that are not registered in organised programmes. Further data on women invited in 2003 were collected as aggregated tables, provided by the local screening registration systems. We obtained data from 99 programmes with an overall target population of 8,698,480 women. At least 70% of programmes could provide data for most indicators. Overall, 3.2% of smears were classified as unsatisfactory. At a national level 6.6% of women was advised to repeat cytology and 62.2% of them actually did. However 13/71 programmes recommended repeat cytology to > 10% of screened women. Nationwide, 2.6% of screened women were referred to colposcopy. The Positive Predictive Value (PPV) of detecting a biopsy-proven Cervical Intraepithelial Neoplasia grade 2 (CIN2) or more severe among women referred because of cytology "Atypical Squamous Cells of Undetermined Significance" or more severe was 15.0%. There was however a relevant variability: 9/90 programmes had a referral rate >5%. There was an inverse correlation between referral rate and PPV. Compliance with recommended colposcopy was 86% (91% among women with high-grade cytology). The raw detection rate of biopsy-proven CIN2+ was 2.7 per 1000 screened women (2.8 per 1000 when standardised on the Italian population). In conclusion, during 2004 there was a further increase of active organised programmes, especially in Southern Italy. This is important, as spontaneous activity is known to be low there. Despite this rise, quality indicators were stable. However, in a few programmes, the use of excessively broad criteria in the interpretation of cytology decides an excessively high rate of referrals to colposcopy.

Incidence rates of adenocarcinoma of the uterine cervix have been reported to be increasing in several countries, but not in Italy. The aim of the present study was to analyse trends in cervical cancer incidence by histological type in two districts of Central Italy (Florence and Prato), covered by the Tuscany Cancer Registry (RTT), where cytological screening had been available since the 1970s. Incident cervical cancers during 1985-2000 were 1012. Estimated Annual Percent Change (EAPC) by age-groups and histological type were computed. Incidence increased for adenocarcinoma (EAPC = +5.7%; 95% confidence interval (CI)+2.8; +8.6); whereas, it decreased for squamous cancer (EAPC = -1.9%; 95% CI-3.8; 0) and for other or not specified types (EAPC = -4.4%; 95% CI-10.0; +1.5). Adenocarcinoma increased significantly among younger women (<55 years) but not among older ones, whereas squamous cell cancer decreased among older women only. The burden of cervical cancers might increase in the future if no specific preventive strategies for adenocarcinoma are implemented.

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.

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.

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.

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.

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.

The authors report on a consecutive retrospective series of 150 male breast cancers. Clinical, diagnostic and therapeutic features are compared over time and with respect to a large consecutive series of female breast cancers. Both age at diagnosis and tumor stage were more advanced in males than in females. Poor alertness of both men and doctors for this infrequent disease may account for such a delay in diagnosis. The use of mammography increased over time and sonography or cytology were frequently and successfully employed in the last decade. Unfortunately no improvement of tumor stage at diagnosis was observed over time in the present series. A time trend was also evident for the type of surgical and postoperative treatment. Modified radical mastectomy and adjuvant chemo- or hormone therapy were increasingly adopted, although Halsted operation and postoperative radiotherapy were still common in the last decade due to the relatively high proportion of locally advanced T3-4 cancers. Both disease-free and overall survival were worse in men than in women, even after adjustment by stage at diagnosis. This study suggests that male breast cancer has a worse prognosis with respect to female breast cancer and provides no complete explanation of this finding, except for an intrinsic higher aggressivity. No evidence was found which may justify a different diagnostic or therapeutic approach with respect to female breast cancer.

The association between "nonclassic" cytologic signs of condyloma and human papillomavirus (HPV) infection in women with negative Papanicolaou smears was analyzed via a case-control study. The cytologic signs considered were mild koilocytosis, mild dyskeratosis, binucleation or multinucleation, cleared cytoplasm and nuclear hyperchromatism. The Papanicolaou smears of 166 cases that showed colposcopic and histologic evidence of HPV infection (but whose smears lacked the classic cytologic signs of condyloma) and 166 controls that were negative colposcopically were randomly admixed and blindly reviewed by a panel of cytologists. A significant association to HPV infection was observed for all of the nonclassic signs studied, but multivariate analysis showed a weakly independent association only for mild koilocytosis. The sensitivity (0.46) and the specificity (0.87) of these nonclassic signs were not satisfactory. The utility of selecting women with negative Papanicolaou smears for colposcopy on the basis of these signs is discussed.