rubrica

Screening

  • Paolo Giorgi Rossi1

  1. Laziosanità, Agenzia di sanità pubblica, Roma
Paolo Giorgi Rossi -

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Ricerca del 15 ottobre 2010

Per leggere (e utilizzare in proprio) questa ROUTINE di ricerca clicca qui

Database: Ovid MEDLINE(R) <1996 to June Week 5 2010> Strategie di ricerca: (exp Mass Screening [MeSH Terms] AND ( Italy [termine libero] OR Italy [MeSH Terms])
Database: Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations Strategia di ricerca: (cancer AND screening) nel campo “title” AND italy nel campo “ Institution”
Limiti: pubblicati da 1gennaio 2010 al 26 ottobre 2010
Esclusi: commentari, editoriali e review narrative; studi multicentrici con PI/primo nome non affiliato in Italia.
Definizione di screening adottata: screening di popolazione a finalità preventive

Di ogni articolo è disponibile l'abstract. Per visualizzarlo basta cliccare sul titolo.

1. Acta Cytologica. 54(3):265-71, 2010 Risk of CIN2 in women with a pap test without endocervical cells vs. those with a negative pap test with endocervical cells: a cohort study with 4.5 years of follow-up. Giorgi Rossi P. Baiocchi D. Ciatto S. Endocervical Cell Italian Working Group of Cervical Cancer Screening Group.
Abstract
OBJECTIVE: To measure the risk of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) in the 4.5 years following a negative Pap smear with adequate endocervical cells (ECC) (+) or absent/scarce ECC (-).
STUDY DESIGN: A prospective, nonconcurrent study of the archives of 11 Italian population-based screening programs was conducted. Only 25-50-year-old women with a first negative Pap test were included. RESULTS: Women were classified as ECC+ or ECC- and followed for 4.5 years. The endpoint was the occurrence of a CIN2+ histologic diagnosis. Eligible subjects with negative Pap tests ECC+ and ECC- numbered 469,694 and 20,596, respectively. At least 1 subsequent test was available during follow-up for 335,763 and 11,972 subjects, and 691 and 13 CIN2+ lesions were observed, respectively. The risk of CIN2+ was 2.06 and 1.09 per 1,000 women over 4.5 years, and age-adjusted relative risk associated with ECC--was 0.55 (95% CI 0.28-1.06).
CONCLUSION: Women with a negative Pap ECC--have a lower risk of CIN2+ than women with a negative Pap ECC+ and should repeat screening with frequency (3-5 years in Europe), independent of age.

Breve commento a cura di Paolo Giorgi Rossi
Quando uno studio cambia le linee guida.

Questo studio multicentrico Italiano promosso dal GISCi chiude una questione aperta ormai da anni: il sistema di refertazione Bethesda 2001 prevede che il Pap test negativo in cui non siano presenti cellule endocervicali sia considerato adeguato. Quando nel 2005 si è adottato il systema Bethesda 2001 In Italia questa indicazione però non è stata accettata dalla comunità dei patologi e citologi italiani che hanno chiesto di fare uno studio locale per verificare se anche qui in Italia il rischio di lesioni Neoplastiche intraepiteliali di alto grado della cervice (CIN2+) dopo Pap test negative mancante di cellule endocervicali fosse molto basso, sebbene la frequenza di questi vetrini sia sostanzialmente più bass ache in Australia dove sono stati fatti la maggior parte degli studi internazionali sui cui si basa la decisione del sistema Bethesda 2001. Lo studio ha raccolto archive da 11 programmi di screening cotenenti 10 milioni di Pap test e seguito per almeno 4.5 anni quasi 500.000 donne di cui 20.000 con vetrini negative mancanti di cellule endocervicali e ha dimostrato che il rischio di CIN2+ dopo queste diagnosi è più basso che nel resto delle donne con Pap test negativo in cui siano visibili cellle endocervicali. Ciò rispecchia probabilmente un minore rischio di infezione da HPV per quelle donne che hanno una zona di transizione fra epitelio squamoso e colonnare più arretrata, donne per le quail il prelievo delle cellule endocervicali è più difficile. La conclusione dello studio ha portato alla modifica delle raccomandazioni italiane: ora dopo un Pap negate mancante di cellule endocervicali la donna deve ripetere il Pap test a scadenza standard, cioè dopo 3 anni.

2. BMC Medicine. 8:11, 2010 Incidence, detection, and tumour stage of breast cancer in a cohort of Italian women with negative screening mammography report recommending early (short-interval) rescreen. Ravaioli A. Foca F. Colamartini A. Falcini F. Naldoni C. Finarelli AC. de Bianchi PS. Bucchi L.
Abstract
BACKGROUND: Although poorly described in the literature, the practice of early (short-interval) rescreen after a negative screening mammogram is controversial due to its financial and psychological burden and because it is of no proven benefit.
METHODS
: The present study targeted an Italian 2-yearly screening programme (Emilia-Romagna Region, 1997-2002). An electronic dataset of 647,876 eligible negative mammography records from 376,257 women aged 50-69 years was record-linked with the regional breast cancer registry. The statistical analysis addressed the following research questions: (1) the prevalence of recommendation for early (< 24 months) rescreen (RES) among negative mammography reports; (2) factors associated with the likelihood of a women receiving RES; and (3) whether women receiving RES and women receiving standard negative reports differed in terms of proportional incidence of interval breast cancer, recall rate at the next rescreen, detection rate of breast cancer at the next rescreen and the odds of having late-stage breast cancer during the interscreening interval and at the next rescreen.
RESULTS
: RES was used in eight out of 13 screening centres, where it was found in 4171 out of 313,320 negative reports (average rate 1.33%; range 0.05%-4.33%). Reports with RES were more likely for women aged 50-59 years versus older women (odds ratio (OR) 1.33; 95% CI 1.25-1.42), for the first versus subsequent screening rounds (OR 1.91; 95% CI 1.79-2.04) and with a centre-specific recall rate below the average of 6.2% (OR 1.41; 95% CI 1.32-1.50). RES predicted a 3.51-fold (95% CI 0.94-9.29) greater proportional incidence of first-year interval cancers, a 1.90-fold (95% CI 1.62-2.22) greater recall rate at the next screen, a 1.72-fold (95% CI 1.01-2.74) greater detection rate of cancer at the next screen and a non-significantly decreased risk of late disease stage (OR 0.59; 95% CI 0.23-1.53).
CONCLUSION: The prevalence of RES was in line with the maximum standard level established by the Italian national guidelines. RES identified a subset of women with greater incidence of interval cancers and greater prevalence of cancers detected at the next screen.

Breve commento a cura di Paolo Giorgi Rossi
Dati routinari + registri tumori = buona ricerca

Dopo le molte pubblicazioni dello studio IMPATTO, ancora i dati routinari di attività degli screening oncologici, insieme ai dati registri tumori forniscono importanti risultati per la letteratura internazionale. Questo lavoro uscito su BMC medicine affronta un problema difficile come I richiami ravvicinati nello screening mammografico, quelle donne cioè che pura avendo una mammografia giudicata negative per lesioni maligne, vengono però reinvitate a fare un successivo esame dopo un anno anzichè dopo 2 anni. L’obiettivo dei programmi di screening è da sempre quello di contenere la quota di richiami ravvicinati sia per il carico di lavoro aggiuntivo che determinano sia per il carico di ansia che generano nella donna. Questo studio dimostra che, in programmi che mantengono questa indicazione a livelli piuttosto bassi (1.3%), effettivamente questa raccomandazione individua un gruppo di donne che ha un rischio maggiore di cancri intervallo e una prevalenza maggiore di cancri invasivi al test successivo.

3. Radiologia Medica. 115(2):238-45, 2010 Advantages of a two-step procedure for school-based scoliosis screening. Leone A. Aulisa A. Perisano C. Re T. Galli M.
Abstract
PURPOSE: To verify if a "two step" school-based scoliosis screening procedure could reduce childhood radiation exposure and, if so, to estimate the subsequent reduction in radiogenic cancer fatalities and in socio-economic burden.
MATERIAL AND METHODS: Data from two different scoliosis screening programs (A and B) performed on a total of 8,995 children (age range 9-14) were examined. Children in program A (5,731 children) were screened using a "two-step" procedure in which school physicians performed the first clinical examination and uncertain cases were referred to an orthopaedist. The school physicians were previously instructed by orthopaedists in the recognition of a number of simple clinical signs. Children in program B (3,264 children) were screened using a "one-step" procedure in which the initial clinical examination was performed directly by an orthopedist. In both programs, suspected cases of scoliosis were then ascertained by the orthopaedist with Radiography. To evaluate the lifetime attributable risk of cancer mortality the guidelines of the International Commission on Radiological Protection Publication 60 were followed. The economic cost of the performed X-ray examination was calculated assuming the current National Health Service's reimbursement to hospitals of euro 35 per X-Ray exam. The statistic significance of the difference in these estimates between the two programs was assessed using the proportions z-test. The issues of the relative sensitivity and specificity of the two programs were also examined.
RESULTS
: In programs A and B, 86 (1.5 %) and 95 (2.91 %) X-ray examinations were performed respectively (z=4.452, p < 0.001). Based on these observations, a screening of 10,000 children directly performed by orthopaedists would result in 291 X-ray exams (2.91 %). A screening of the same number of children using a two-step procedure would result in 150 X-ray exams (1.5 %), with a savings of euro 4,935 for the National Health Care System, a reduction of 0.283 Sv of collective dose, and an estimated 50% reduction in the number of radiogenic malignant tumours.
CONCLUSIONS
: Using a two-step scoliosis screening procedure provides reasonable sensitivity and specificity while reducing costs and radiation exposure to children.
4. Pediatric Infectious Disease Journal. 29(2):115-21, 2010. Group B Streptococcus early-onset disease in Emilia-romagna: review after introduction of a screening-based approach. Berardi A. Lugli L. Baronciani D. Rossi C. Ciccia M. Creti R. Gambini L. Mariani S. Papa I. Tridapalli E. Vagnarelli F. Ferrari F. GBS Prevention Working Group of Emilia-Romagna.
Abstract
BACKGROUND: Group B Streptococcus (GBS) is a leading cause of neonatal bacterial infections. Early-onset infections have decreased in recent years but, despite considerable efforts poured into prevention, cases continue to occur.
OBJECTIVES
: To analyze trends and identify determining factors for the persistence of the GBS infections. To evaluate the impact of antenatal screening and intrapartum chemoprophylaxis on the clinical presentation of the infection. METHODS: A prospective cohort, population-based study has been ongoing in Emilia-Romagna (Italy) since 2003. Invasive GBS infections, observed between 2003 and 2008 in infants aged < 7 days were analyzed.
RESULTS
: Among 214,120 live births, 61 early-infections were observed. Fourteen infants (23.0%) were born preterm. Among 47 infants who were delivered at term, 28 were born to mothers who had no risk factors and 7 were born to mothers who had none other than GBS colonization. Forty-one women at term had been screened prenatally; among them, only 10 were documented as GBS culture-positive.Disease severity was highest in infants at lower gestational ages, but most meningitis cases were observed in term infants born to mothers who were GBS culture-negative at screening.Nine newborns had culture-proven infection despite having received intrapartum antibiotics. They were born to mothers with > or =1 obstetrical risk factors and 5 mothers had been treated during labor with macrolides.
CONCLUSION: Most infections presented in infants whose mothers had been screened as GBS culture-negative. Missed opportunities for prevention contributed more than prophylaxis failures to the early-onset disease burden.
5. Endoscopy. 42(1):15-21, 2010 High uptake of colonoscopy in first-degree relatives of patients with colorectal cancer in a healthcare region: a population-based, prospective study. Armelao F. Orlandi PG. Tasini E. Franceschini G. Franch R. Paternolli C. de Pretis G.
Abstract
BACKGROUND AND STUDY AIMS: A screening program in first-degree relatives (FDRs) of colorectal cancer (CRC) patients (index patients) was started in Trentino, Italy, to analyze factors that influence uptake of CRC screening among invited FDRs (first objective) and to describe colorectal findings among those undergoing colonoscopy (secondary objective).
PATIENTS AND METHODS
: FDRs aged between 45 and 75 years were invited; exclusion criteria were: colonoscopy or barium enema in the preceding 5 years, a history of familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, inflammatory bowel diseases, and severe comorbidities. FDRs who were eligible but were not invited for screening because consent was not obtained from the index patients were considered as the control group. FDRs were invited by the education campaign targeted at the population at risk (both study and control groups); in the study group, interventions targeting individuals at risk (letters, phone calls, face-to-face counseling) were implemented.
RESULTS
: Starting from 626 new index cases of diagnosed CRC, 725 FDRs were invited to counseling; 77.6 % of these attended for colonoscopy in the study group vs. 8 % in the control group ( P < 0.0001). Predictors of colonoscopy uptake were FDR age above 60 years [odds ratio (OR) 2.50, 95 %CI 1.72 - 3.62], complex family history (simple family history: one CRC at age above 60 years; complex family history: one CRC at age below 60 or two or more CRC; OR 1.54; 95 %CI 1.04 - 2.33) and living in a rural area (OR 1.64, 95 %CI 1.12 - 2.44). Of the 560 FDRs in the study group, 186 (33.8 %) had adenomas, and 48 (8.8 %) had advanced adenomas or cancer.
CONCLUSIONS
: Interventions that target FDRs of patients with CRC, especially those younger than 60 years, with a complex family history of CRC and who live in a rural area, may improve uptake of CRC screening via colonoscopy.
6. International Psychogeriatrics. 22(1):82-90, 2010 The validation of the Italian version of the GPCOG (GPCOG-It): a contribution to cross-national implementation of a screening test for dementia in general practice. Pirani A. Brodaty H. Martini E. Zaccherini D. Neviani F. Neri M.
Abstract
BACKGROUND: The General Practitioner Cognitive Assessment of Cognition (GPCOG), a brief, efficient dementia-screening instrument for use by general practitioners (GPs), consists of cognitive test items and historical questions asked of an informant. The validity of instruments across different cultures and languages requires confirmation and so the aim of this study was to validate the Italian version of GPCOG (GPCOG-It).
METHODS
: The validity of the GPCOG-It was assessed against standard criteria for diagnosis of dementia (Diagnostic and Statistical Manual of Mental Disorders - 4th edition) as well as the Clinical Dementia Rating scale. The participants comprised 200 community-dwelling patients aged at least 55 years with (patient group) or without memory complaints (control group). Seven general practitioners were involved. Measurements used were the Cambridge Cognitive Assessment, Mini-mental State Examination with standard (24/25) and Italian cut-off (26/27), Alzheimer's Disease Assessment Scale-Cognitive scale and Geriatric Depression Scale.
RESULTS: The GPCOG-It, total score and two-stage method, were at least equivalent in detecting dementia to the MMSE using the standard 24/25 or the Italian 26/27 cut-offs. The two-stage method of administering the GPCOG-It (cognitive testing followed by informant questions if necessary) had a sensitivity of 82%, a specificity of 92%, a misclassification rate of 17.4% and positive predictive value of 95%. Patient interviews took less than 4 minutes to administer and informant interviews less than 2 minutes, half the time needed for MMSE administration.
CONCLUSIONS: GPCOG-It maintains the same psychometric features and time efficiency as the original English version. Despite methodological limitations (i.e. use of defined samples), the GPCOG-It performed well in detecting clear cut and borderline cognitively impaired patients and can be introduced in the daily practice of Italian GPs.
7. Archives of Gerontology & Geriatrics. 50(1):105-9, 2010 A combination of glycosylated hemoglobin, impaired fasting glucose and waist circumference is effective in screening for individuals at risk for future type 2 diabetes. Motta M. Bennati E. Cardillo E. Ferlito L. Passamonte M. Vacante M. Malaguarnera M.
Abstract
The diabetes mellitus of type 2 (DMT2) is a disease of the elderly with multifactorial pathogenesis, characterized by interactions of genetic variations suspect for diabetes, as well as of the longevity and aging genes. Since today it is still not possible to obtain the diagnosis with laboratory methods of clinical genetics, we tried to identify the subjects of risk of future diabetes on the basis of a combined measurement of glycemia, the glycosylated hemoglobin (HbA1c) and the waist circumference (WC). The studied population consisted of 2603 elderly subjects of 65-84 years of age, involved in the epidemiological study called ILSA (Italian Longitudinal Study on Aging). The subjects who displayed at the baseline an impaired fasting glucose (IFG) accompanied by HbA1c and WC values above the normal cut-points proved to be diabetic after a 3-year follow-up in 18.96%, while the subjects with normal fasting glucose (NFG) accompanied by normal HbA1c and WC values were found to be diabetic only in 1.34%. It means that the presence of abnormal values of these 3 parameters in the elderly does not allow the identification of the risks for future diabetes in the great majority of subjects. We conclude that the results of prospective studies may gain particular significance not only regarding the glycemia, but also the other 2 risk factors, if we wish to reach not only a predictive diagnosis of risk for diabetes, but also to prevent the chronic degenerative complications of it.
8. Hypertension. 55(1):83-9, 2010 Within-patient reproducibility of the aldosterone: renin ratio in primary aldosteronism. Rossi GP. Seccia TM. Palumbo G. Belfiore A. Bernini G. Caridi G. Desideri G. Fabris B. Ferri C. Giacchetti G. Letizia C. Maccario M. Mallamaci F. Mannelli M. Patalano A. Rizzoni D. Rossi E. Pessina AC. Mantero F. Primary Aldosteronism in the Prevalence in hYpertension (PAPY) Study Investigators.
Abstract
The plasma aldosterone concentration:renin ratio (ARR) is widely used for the screening of primary aldosteronism, but its reproducibility is unknown. We, therefore, investigated the within-patient reproducibility of the ARR in a prospective multicenter study of consecutive hypertensive patients referred to specialized centers for hypertension in Italy. After the patients were carefully prepared from the pharmacological standpoint, the ARR was determined at baseline in 1136 patients and repeated after, on average, 4 weeks in the patients who had initially an ARR > or =40 and in 1 of every 4 of those with an ARR < 40. The reproducibility of the ARR was assessed with Passing and Bablok and Deming regression, coefficient of reproducibility, and Bland-Altman and Mountain plots. Within-patient ARR comparison was available in 268 patients, of whom 49 had an aldosterone-producing adenoma, on the basis of the "4-corner criteria." The ARR showed a highly significant within-patient correlation (r=0.69; P < 0.0001) and reproducibility. Bland-Altman plot showed no proportional, magnitude-related, or absolute systematic error between the ARR; moreover, only 7% of the values, for example, slightly more than what could be expected by chance, fell out of the 95% CI for the between-test difference. The accuracy of each ARR for pinpointing aldosterone-producing adenoma patients was approximately 80%. Thus, although it was performed under different conditions in a multicenter study, the ARR showed a good within-patient reproducibility. Hence, contrary to previously claimed poor reproducibility of the ARR, these data support its use for the screening of primary aldosteronism.

Breve commento a cura di Paolo Giorgi Rossi.
Dati routinari + registri tumori = buona ricerca valutativa

Nella produzione scientifica italiana riguardante gli screening di popolazione nel corso del 2010 gli screening oncologici sono decisamente più studiati (17/22) quelli neonatali o scolastici (un solo studio sulla prevenzione della meningite da streptococco post partum e uno sulla scoliosi) o di altre malattie croniche nell’adulto (uno studio sulle demenze, uno sul diabete e uno sull’ipertensione). Fra gli oncologici, oltre ai tre screening già implementati (mammella 4 studi, cervice uterina 3 studi, e colonretto 7 studi), tre studi riguardano sperimentazioni e validazione di test per lo screening del polmone. Abbiamo trovato quattro studi basati su dati trial, mentre il resto sono tutti studi osservazionali ad eccezione di un modello di costo efficacia. Sorprendentemente gli studi sugli screening oncologici vedono una scarsa produzione da parte di IRCCS e Università (4/22), mentre molti studi sono prodotti direttamente da chi gestisce ed eroga I programmi di screening, spesso in strutture territoriali la cui mission principale non è certo la ricerca. Dopo le molte pubblicazioni dello studio IMPATTO, ancora i dati routinari di attività degli screening oncologici, insieme ai dati registri tumori forniscono importanti risultati per la letteratura internazionale con sei studi basati su queste banche dati. In particolare il lavoro uscito su BMC medicine ad opera del gruppo dell’Emilia Romagna (Ravaioli et al) affronta un problema difficile come I richiami ravvicinati nello screening mammografico, quelle donne cioè che pura avendo una mammografia giudicata negativa per lesioni maligne, vengono però re-invitate a fare un successivo esame dopo un anno anziché dopo 2 anni. Un obiettivo dei programmi di screening è da sempre quello di contenere la quota di richiami ravvicinati sia per il carico di lavoro aggiuntivo che determinano sia per il carico di ansia che generano nella donna. Questo studio dimostra che, in programmi che mantengono un tasso di richiami ravvicinati molto basso (1.3%), effettivamente le donne richiamate hanno un rischio maggiore di cancri intervallo e una prevalenza maggiore di cancri invasivi al test successivo. Segnaliamo un secondo studio basato sui dati routinari degli screening linkati con i dati delle anatomie patologiche, per il percorso di produzione delle evidenze e modifica delle linee guida che lo ha caratterizzato. Lo studio sull’assenza di cellule endocervicali, voluto e promosso dal GISCi (Gruppo Italiano Screening Citologico) (Giorgi Rossi et al.) chiude una questione aperta ormai da anni: il sistema di refertazione Bethesda 2001 prevede che il Pap test negativo in cui non siano presenti cellule endocervicali sia considerato adeguato. Quando nel 2005 si è adottato il sistema Bethesda 2001 In Italia, la comunità dei patologi e citologi non ha accettato questa indicazione, chiedendo e promuovendo uno studio che producesse evidenze per la realtà dei programmi di screening italiani. Lo studio ha dimostrato che il rischio di lesioni precancerose di alto grado della cervice uterina in donne con una diagnosi di Pap test negativo in assenza di cellule endocervicali è più basso che nel resto delle donne con Pap test negativo. La conclusione dello studio ha portato alla modifica delle raccomandazioni italiane: ora dopo un Pap negate mancante di cellule endocervicali la donna deve ripetere il Pap test a scadenza standard, cioè dopo 3 anni.

9. Eur J Cancer. 2010 Oct 11. [Epub ahead of print] Up-to-date estimates of breast cancer survival for the years 2000-2004 in 11 European countries: The role of screening and a comparison with data from the United States. Rosso S, Gondos A, Zanetti R, Bray F, Zakelj M, Zagar T, Smailyte G, Ponti A, Brewster DH, Voogd AC, Crocetti E, Brenner H; the EUNICE Survival Working Group.
Abstract
INTRODUCTION: We investigated survival in breast cancer patients by age group, focussing on those covered by screening programmes, using data from 12 European population-based cancer registries participating in the European Network for Indicators on Cancer Survival Working Group.
METHODS: We calculated period estimates of 5-year relative survival for 2000-2004 and examined the change in survival estimates for four age groups between 1990-1994 and 2000-2004. Trends in age specific incidence, survival and mortality were additionally compared to those in the United States based on results from the Surveillance Epidemiology and End Results (SEER) programme.
RESULTS: Breast cancer survival uniformly increased particularly in areas with lower breast cancer survival for patients diagnosed in 1990-1994. With the exception of Geneva, Scotland and Estonia, the rise in survival was always larger among the younger age groups than in the 70+ age group and the age-gradient widened over time. The 5-year relative survival of patients aged 70 and above in the European registries was at least 7 percentage points lower than the 5-year relative survival of patients in the same age group in the US in 2000-2004. During the study period, incidence increased in all age groups and populations with a few exceptions, an observation paralleled by declining mortality.
CONCLUSIONS: Results showed that some of the geographical differences in overall survival are even larger when considering age groups, in particular between Western and Eastern European countries. Furthermore, some of the differences in survival within the Northern and Western European areas could be due to variations in the implementation of screening programmes rather than economic inequalities.
10. Cancer Cytopathol. 2010 Aug 25;118(4):203-8. Accuracy of liquid-based cytology: comparison of the results obtained within a randomized controlled trial (the New Technologies for Cervical Cancer Screening Study) and an external group of experts. Confortini M, Bergeron C, Desai M, Negri G, Dalla Palma P, Montanari G, Pellegrini A, Ronco G; New Technologies for Cervical Cancer Screening Study Cytology Group.
Collaborators: Parisio F, Ghiringhello B, MinuccI D, Onnis GL, Matteucci M, Lestani M, Vignato A, Pojer A, Pierotti P, Bondi A, Sintoni C, Cariaggi P, Raggi P, Schiboni ML.
Abstract
BACKGROUND: In the New Technologies for Cervical Cancer Screening (NTCC) randomized controlled trial, no significant increase in the sensitivity of liquid-based cytology (LBC) was observed compared with conventional cytology.Both were interpreted by cytologists who had limited previous LBC experience. The objective of the current study was to assess whether different results could be expected with experienced LBC interpreters.
METHODS: A stratified, random sample of 818 LBC slides from the NTCC study was obtained. These slides were reviewed blindly and independently by 3 international experts who did not participate in the NTCC. The sensitivity and specificity of external experts were estimated for cervical intraepithelial neoplasia grade 2 or greater (CIN2+) and for CIN3+ histology, and the differences were compared with the sensitivity and specificity of the original cytologic interpretation using cutoffs of atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL).
RESULTS: With the endpoint of CIN2+ histology, the difference in sensitivity between external experts and the original interpretation was -5.3 (95% confidence interval [CI], -16.0 to 5.4) with ASCUS as the cutoff and 3.8 (95% CI, -8.2 to 15.8) with LSIL as the cutoff. External experts had slightly lower specificity using ASCUS as the cutoff (-3.4; 95% CI, -3.9 to -2.9) and LSIL as the cutoff (-0.7; 95% CI, -1.0 to -0.4).
CONCLUSIONS: The accuracy of the external experts' interpretation was similar to that of the original interpretation. Therefore, the current results indicated that LBC is not expected to increase sensitivity even if it is used by interpreters who have extensive experience with this technique.
11. Eur J Obstet Gynecol Reprod Biol. 2010 Oct;152(2):200-4. Epub 2010 Jul 27. Screening history of women with invasive cervical cancer in north-east Italy. Zucchetto A, Franceschi S, Clagnan E, Serraino D, Zanier L, Franzo A; Friuli Venezia Giulia Cancer Registry Working Group. Collaborators: de Dottori M, De Paoli A, Lise M, Forgiarini O, Angelin T, De Santis E.
Abstract
OBJECTIVES: To describe screening histories of women with invasive cervical cancer (ICC) in Friuli Venezia Giulia, after the introduction of organized screening, in order to identify possible reasons undermining prevention of ICC. To investigate associations between screening histories in relation to women's survival and tumor characteristics, with a focus on organized and opportunistic screenings.
STUDY DESIGN: 438 women, diagnosed with ICC between 1999 and 2005,were identified using the regional Cancer Registry. Cytological and histopathological information were obtained through regional health databases. Associations between different screening histories and characteristics of women and their tumors were evaluated by means of odds ratios (OR) and corresponding 95% confidence intervals (CI), through multinomial logistic regression models adjusted for age; death risks were estimated by computing hazard ratios (HR) with 95% CI, using Cox models adjusted for age, tumor stage, and histology.
RESULTS: 165 (38%) women with ICC had no Pap smears: 71 (16%) never attended the organized screening despite invitation; 69 (16%) were never invited because they were above 64 years of age; and 25 (6%) were yet to be invited. Conversely, 273 (62%) women underwent screening: 141 women (32%) had opportunistic screening; 132 (30%) women attended the organized program. A total of 193 (44%) women had ICC detected at screening. Compared to women with ICC who had never been screened, those screened within the organized program were more often at stage IA (46%), were seldom at stage II or higher (OR=0.3, 95% CI: 0.1-0.6, vs. IB), and showed a lower risk of death (HR=0.6, 95% CI: 0.3-1.0).
CONCLUSIONS: In Friuli Venezia Giulia, the lack of screening among older women and of compliance with organized programs among women in the target population are the main limitations in cervical cancer secondary prevention. Our findings indicate that participation in organized screening has a beneficial effect in terms of down-staging and improved survival as compared to both absence of screening and opportunistic screening.
12. Clin Gastroenterol Hepatol. 2010 Oct;8(10):865-9, 869.e1-3. Epub 2010 Jun 1. A resect and discard strategy would improve cost-effectiveness of colorectal cancer screening. Hassan C, Pickhardt PJ, Rex DK.
Abstract
BACKGROUND & AIMS: A "resect and discard" policy has been proposed for diminutive polyps detected by screening colonoscopy, because hyperplastic and adenomatous polyps can be distinguished, in vivo, by using narrow-band imaging (NBI). We modeled the cost-effectiveness of this policy.
METHODS: Markov modeling was used to compare the cost-effectiveness of universal pathology evaluations with a resect and discard policy for colonoscopy screening. In a resect and discard approach, diminutive lesions (≤5 mm), classified by endoscopy with high confidence, were not analyzed by a pathologist. Base case assumptions of an 84% rate of high-confidence classification, with a sensitivity and specificity for adenomas of 94% and 89%, respectively, were used. Census data were used to project outputs of the model onto the US population, assuming 23% as the current rate of adherence to a colonoscopy screening.
RESULTS: With universal referral of resected polyps to pathology, colonoscopy screening costs an estimated $3222/person, with a gain of 51 days/person. Endoscopic polypectomy accounted for $179/person, of which $46/person was related to pathology examination. Adoption of a resect and discard policy for eligible diminutive polyps resulted in a savings of $25/person, without any meaningful effect on screening efficacy. Projected onto the US population, this approach would result in an undiscounted annual savings of $33 million. In the sensitivity analysis, the rate of high-confidence diagnosis and the accuracy for endoscopic polyp determination were the most meaningful variables.
CONCLUSIONS: In a simulation model, a resect and discard strategy for diminutive polyps detected by screening colonoscopy resulted in a substantial economic benefit without an impact on efficacy.
13. Gut. 2010 Nov;59(11):1511-5. Epub 2010 Jul 5. Influence of seasonal variations in ambient temperatures on performance of immunochemical faecal occult blood test for colorectal cancer screening: observational study from the Florence district. Grazzini G, Ventura L, Zappa M, Ciatto S, Confortini M, Rapi S, Rubeca T, Visioli CB, Halloran SP. Comment in: Gut. 2010 Nov;59(11):1451-2.
Abstract
BACKGROUND: Faecal occult blood testing (FOBT) in population screening has proved to be effective in reducing mortality from colorectal cancer. In Italy a latex agglutination FOBT has been adopted for a single-sample screening programme. The aim of this study was to examine the performance of FOBTs in the Florence screening programme over several seasons to evaluate the impact of variations in ambient temperature on the performance of the screening test.
METHODS: Measured haemoglobin (Hb) concentrations were aggregated into seasons with their average ambient temperature (AAT). Using logistic regression, the AAT over the period preceding the test measurement was analysed. This period included the time between faecal sampling and return of the test sample (mean 7days) and the time in the laboratory refrigerator before analysis (mean 4days). The AAT from days 5-11 before analysis of the test sample was considered a determinant of test positivity. The Kruskal-Wallis rank test was used to evaluate the significance of seasonal and/or AAT-related differences in Hb concentration. A logistic regression model adjusted for sex, age, season and screening episode (first or repeated examination) was constructed.
RESULTS: 199 654 FOBT results were examined. Mean FOBT seasonal Hb concentrations (ng/ml) were: spring 27.6 (95% CI 26.2 to 29.1); summer 25.2 (95% CI 23.1 to 27.3); autumn 29.2 (95% CI 27.7 to 30.6); winter 29.5 (95% CI 27.9 to 31.1). Logistic regression showed that there was a 17% lower probability of the FOBT being positive in summer than in winter. The results of the logistic regression showed that an increase in temperature of 1°C produced a 0.7% reduction in probability of a FOBT being positive. In the summer the probability of detecting a cancer or an advanced adenoma was about 13% lower than in the winter.
CONCLUSIONS: This study showed that there is a significant fall in Hb concentration at higher ambient temperatures. These results will have important implications for the organisation of immunochemical FOBT-based screening programmes, particularly in countries with high ambient temperatures.
14. Breast J. 2010 Jul;16(4):350-5. Epub 2010 Apr 23. Disentangling the roles of mammographic screening and HRT in recent breast cancer incidence trends in italy by analyses based on calendar time and time since screening activation. Crocetti E, Buzzoni C, Falcini F, Cortesi L, De Lisi V, Ferretti S, Tumino R, Russo A, Paci E.
Abstract
The aim of the study was to evaluate the roles of screening activation and hormone replacement therapy discontinuation on the recent declining breast cancer incidence trends in Italy. We analyzed 41,358 invasive female breast cancers incident during 1991-2004 in six Italian population-based cancer registries. Overall and age-specific incidence trends were evaluated using Joinpoint analysis. In addition to calendar years, data were analyzed on a years-since-screening-activation basis. Annual percentage change of standardized rates was computed. There were statistically significant increasing trends for women 40-44 and 45-49 years that did not change after screening activation. On the contrary, for women 50-69 years old and for those 70+ years, the increasing trends flattened around 2 years after screening activation. The prevalence of hormone replacement therapy use in Italy is and was rather low. In conclusion, the recent tendency toward stabilization observed in Italy for female breast cancer incidence rates in women aged 50 years or more follows the introduction of mammographic screening.
15. Abdom Imaging. 2010 Oct;35(5):596-601. Epub 2009 Sep 24. CT colonography versus double-contrast barium enema for screening of colorectal cancer: comparison of radiation burden. Neri E, Faggioni L, Cerri F, Turini F, Angeli S, Cini L, Perrone F, Paolicchi F, Bartolozzi C.
Abstract
Our aim is to compare the radiation dose associated with a low-dose CT colonography (CTC) protocol for colorectal cancer screening with that delivered by double-contrast barium enema (DCBE). CTC of twenty asymptomatic individuals (M:F = 10:10) participating to a colorectal cancer screening program and DCBE of fifteen patients (M:F = 6:9) were evaluated. For CTC, absorbed dose was determined by calculating the dose-length product for each CTC examination from measurements on a CT dose phantom equipped with a CT ion chamber. For DCBE, the free-in-air Kerma at the patient's X-ray entry surface and the Kerma-area product during fluoroscopy and fluorography were measured with a Barracuda system, with fluoroscopy times being recorded blinded to the performing operator. Effective dose at CTC was 2.17 ± 0.12 mSv, with good and excellent image quality in 14/20 (70%) and 6/20 cases (30%), respectively. With DCBE, effective patient dose was 4.12 ± 0.17 mSv, 1.9 times greater than CTC (P < 0.0001). Our results show that effective dose from screening CTC is substantially lower than that from DCBE suggesting that CTC is the radiological imaging technique of the large bowel with the lowest risk of stochastic radiation effects.
16. Dis Colon Rectum. 2010 Sep;53(9):1328-33. Impact of lifestyle factors on colorectal polyp detection in the screening setting. Hassan C, Pickhardt PJ, Marmo R, Choi JR.
Abstract
BACKGROUND: Awareness of risk factors for colorectal neoplasia could address risk reduction strategies in asymptomatic subjects.
METHODS: This is a post hoc analysis of a prospective, cross-sectional study of 1321 asymptomatic adults. All the subjects underwent same-day CT colonography and colonoscopy to determine the prevalence of colorectal neoplasia. The variables examined included body mass index, smoking, alcohol consumption, age, and gender. Univariate and logistic regression analyses were performed for detection of colorectal neoplasia and hyperplastic polyps. Odds ratios with 95% confidence intervals were calculated.
RESULTS: Colorectal adenomas and hyperplastic polyps were detected in 378 (28.6%) and 157 (11.9%) participants, respectively. In both univariate and multivariate analysis, increasing age, male gender, and body mass index > or =25 were significantly associated with the detection of colorectal adenomas, with an odds ratio of 1.22 (95% CI,1.09-1.36), 1.28 (95% CI, 1.06-1.45), and 1.34 (95% CI, 1.02-1.77), respectively. A history of smoking was the only identifiable risk factor for hyperplastic polyps (odds ratio, 1.98; 95% CI, 1.41-2.78).
CONCLUSIONS: Body mass index > or =25, increasing age, and male gender were all associated with an increased likelihood of colorectal adenomas at screening,whereas smoking was strongly associated with hyperplastic polyps.
17. Digestive & Liver Disease. 42(5):371-6, 2010. Participation in colorectal cancer screening with FOBT and colonoscopy: an Italian, multicentre, randomized population study. Lisi D. Hassan CC. Crespi M. AMOD Study Group.
Abstract
BACKGROUND: Data on the adherence rate to screening colonoscopy (OC) in the average-risk general population are limited and variable. Aim of this study was to compare the uptake of OC screening with that of fecal occult blood (FOBT).
METHODS: A nationwide, population-based, multicentre, randomized trial comparing attendance to OC with that to FOBT was performed. Sixty-four general practitioners (GPs), overall including in their lists 9889 average-risk subjects aged 55-64 years, were randomized between OC and FOBT screening programs. Eligible subjects were mailed a personal invitation letter co-signed by their GP and the coordinator of the area-reference GI centre. Attendance rate and detection rate for advanced neoplasia (colorectal cancer, adenoma >10mm or with villous histology or high-grade dysplasia) for each arm of the study were assessed.
RESULTS: The overall attendance rate was 18.7% (1563/8378 eligible subjects). It was markedly lower in the OC than in the FOBT strategy (10% vs. 27.1%; OR 0.28, 95% CI: 0.25-0.32; P < 0.0001). In particular, participation in OC screening arm was extremely low in South Italy (2.8%), whilst it was higher in North-Central Italy (12.4%; P < 0.0001). Compliance to colonoscopy in those with a positive FOBT was only 58%. Advanced neoplasia was detected in 28 (6.8%) patients in the OC arm and in 6 (18%) in those with a positive FOBT submitted to OC.
CONCLUSIONS: The results of our study underline the difficulties and barriers to implement a OC population screening in Italy, at least through primary care. Although attendance to FOBT was higher, it was disappointingly less than 30%. Significant actions to improve awareness amongst GPs and the population are a high priority.
18. Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer. 5(4):428-35, 2010 Self-selection effects in smokers attending lung cancer screening: a 9.5-year population-based cohort study in Varese, Italy. Dominioni L, Rotolo N, Poli A, Paolucci M, Sessa F, D'Ambrosio V, Paddeu A, Mantovani W, Imperatori A.
Abstract
BACKGROUND: We hypothesize that mortality risk profile of participants and nonparticipants in nonrandomized lung cancer (LC) screening of smokers may be different.
METHODS
: In 1997, a population-based cohort of 5815 smokers of Varese Province was invited to nonrandomized LC screening by annual chest x-ray examination for 4 years. LC risk factors and screening participation rate were recorded. Except for screening, the whole cohort received usual care. After 9.5-year observation, we compared mortality of participants versus nonparticipants by assessing age-standardized all-cause mortality rate ratio (MRR) and disease group-specific MRR with 95% confidence intervals (95% CI).
RESULTS
: Self-selected screening participants were 21% of cohort. Participants were younger (p < 0.001), were more frequently current smokers (p = 0.019), had more pack-years of smoking (p < 0.0001), and had higher rate of LC family history (p < 0.0001) and of occupational LC risk (p < 0.0001) relative to nonparticipants. In logistic regression analysis familial LC, occupational risk and pack-years smoked were significant predictors of participation in screening and of developing LC. Participants displayed a healthy effect, as shown by all-cause MRR = 0.67 (95% CI, 0.53-0.84), all cancers except LC MRR = 0.61 (95% CI, 0.41-0.91), cardiovascular diseases MRR = 0.38 (95% CI, 0.22-0.63), and noncancer disease other than cardiovascular or respiratory MRR = 0.57 (95% CI, 0.34-0.92). The LC mortality (MRR = 1.40; 95% CI, 1.03-1.91) was higher in participants relative to nonparticipants (p = 0.031).
CONCLUSION: The selection effect in LC screening participants was dual: healthy effect and higher LC mortality. In assessing the overall effectiveness of LC screening on a population level, a higher LC mortality risk in participants should be considered.
19. Lung Cancer. 68(2):216-21, 2010 Molecular profile in body fluids in subjects enrolled in a randomised trial for lung cancer screening: Perspectives of integrated strategies for early diagnosis. Carozzi FM. Bisanzi S. Falini P. Sani C. Venturini G. Lopes Pegna A. Bianchi R. Ronchi C. Picozzi G. Mascalchi M. Carrozzi L. Baliva F. Pistelli F. Tavanti L. Falaschi F. Grazzini M. Innocenti F. Paci E. ITALUNG Study Research group
Abstract
The aim of this study was to evaluate the diagnostic value of a grid of molecular genetic markers detectable in sputum and plasma samples of individuals enrolled in a lung cancer screening program with low-dose CT. Subjects enrolled in the baseline screening round of the ITALUNG (randomised) screening trial were invited to provide biological specimens for molecular analysis (1356 subjects out of 1406). We included 98 subjects in this analysis. There was a highly statistically significant difference between proportion of subjects with a negative baseline CT screening test who were positive to allelic imbalance, and those with a non-calcified nodule (NCN greater than or equal to 5mm), the reason of recall for all suspects at CT Scan (chi(2): 22.9; P<0.0001). Allelic imbalance showed good performance for screening of NCN > or = 5 mm. In subjects recalled for NCN > or = 5 mm, LOH, K-ras mutations and high levels of free plasma DNA (>5ng/ml plasma) might be important to support clinical decision making for further follow-up and repeated screening. This study, embedded in an early diagnosis randomised trial, suggests that a multi-screening approach integrating imaging technique and a biomolecular marker panel is worth of further investigation.
20. Tumori. 96(2):198-201, 2010 Interval cancers in breast cancer screening: comparison of stage and biological characteristics with screen-detected cancers or incident cancers in the absence of screening. Caumo F. Vecchiato F. Strabbioli M. Zorzi M. Baracco S. Ciatto S.
Abstract
AIMS AND BACKGROUND: To analyze stage distribution and biological features of interval cancers observed in Verona mammography screening compared to screen-detected cancers and "clinical" cancers occurring in the absence of screening, as provided by the Veneto Cancer Registry.
METHODS AND STUDY DESIGN: Screen-detected cancers were identified in the screening archives. Interval cancers and clinical cancers (occurring in women never screened or not yet invited) were identified through the local cancer registry. Studied variables were age, stage, pathological pT and pN category, histological grading, estrogen and progesterone receptor status, and proliferation index (Ki67).
RESULTS: We compared 95 interval cancers, 761 screen-detected cancers, and 1873 clinical cancer cases. Interval cancers had more aggressive features than screen-detected cancers, the difference being statistically significant for pT (P=106), pN (P = 0.0003), grading (P = 0.007), estrogen receptors (P = 0.0006), and progesterone receptors (P = 0.00005), but not for Ki67 (P = 0.18). The features of interval cancers were not more aggressive than those of clinical cancers for pT (P = 0.84), pN (P = 0.33), grading (P = 0.61), estrogen receptors (P = 0.48), and progesterone receptors (P = 0.69), and were better for Ki67 (P = 0.02). In contrast, screen-detected cancers showed significantly better features than clinical cancers, for all studied variables: pT (P = 10(-6)), pN (P = 10(-6)), grading (P = 10(-6)), estrogen receptors (P = 10(-5)), progesterone receptors (P = 10(-6)), and Ki67 (P = 10(-6)).
CONCLUSIONS: Our findings are consistent with the length biased sampling hypothesis of interval cancers having a faster growth rate and a less favorable presentation than screen-detected cancers. Compared to clinical cancers, interval cancers had similar features, whereas screen-detected cancers had definitely more favorable features. This finding suggests, rather than a faster growth rate for interval cancers, a slower growth rate for screen-detected cancers, which, together with diagnostic anticipation, may explain a certain degree of overdiagnosis.
21. European Respiratory Journal. 35(1):146-51, 2010. Lung function predicts lung cancer risk in smokers: a tool for targeting screening programmes. Calabro E. Randi G. La Vecchia C. Sverzellati N. Marchiano A. Villani M. Zompatori M. Cassandro R. Harari S. Pastorino U.
Abstract
The relationship between smoking, lung cancer and airflow obstruction is recognised but it is unclear whether the presence of minimal lung function damage constitutes an independent risk factor for the development of lung cancer. In order to identify those individuals at higher risk of lung cancer on the basis of functional impairment, we evaluated baseline pulmonary function tests of 3,806 heavy smokers undergoing annual chest computed tomography screening, and compared the forced expiratory volume in 1 s (FEV(1)) % predicted of 57 lung cancer cases and that of 3,749 subjects without cancer. We obtained odds ratios (ORs) of lung cancer and the corresponding 95% confidence intervals (CIs) using unconditional logistic regression, adjusting for age, sex, study and smoking variables. Compared with subjects with FEV(1) >or=90% pred, the OR of lung cancer was 2.45 (95% CI 1.39-4.33) for subjects with FEV(1) < 90% pred and 2.90 (95% CI 1.34-6.27) for subjects with FEV(1) <70% pred. These data show that even a relatively small reduction in FEV(1) % pred is a significant predictor of increased lung cancer risk. Test screening for lung cancer using airflow obstruction with FEV(1) <90% is a strategy worth future consideration.
22. American Journal of Gastroenterology. 105(1):188-98, 2010 Senore C. Comparing different strategies for colorectal cancer screening in Italy: predictors of patients' participation. Armaroli P. Silvani M. Andreoni B. Bisanti L. Marai L. Castiglione G. Grazzini G. Taddei S. Gasperoni S. Giuliani O. Malfitana G. Marutti A. Genta G. Segnan N.
Abstract
OBJECTIVES: The objective of this study was to study predictors of patients' participation in colorectal cancer (CRC) screening.
METHODS: Men and women, aged 55-64 years, were randomized to the following: (i) biennial fecal occult blood test (FOBT) delivered by mail (n=2,266); (ii) FOBT delivered by a general practitioner (GP)/screening facility (n=5,893); (iii) "once-only" sigmoidoscopy (FS) (n=3,650); (iv) FS followed by FOBT for screenees with negative FS (n=10,867); and (v) patient's choice between FS and FOBT (n=3,579). A stratified (by screening arm) random sample of attenders and nonattenders was contacted by trained interviewers 4 months after the initial invitation. Subjects giving their consent were administered a questionnaire (available online) investigating perceptions of individual CRC risk, attitudes toward prevention, adoption of health protective behaviors, and reasons for attendance/nonattendance. Adjusted prevalence odds ratios (ORs) were computed by multivariable logistic regression.
RESULTS: The response rate was 71.9% (701 of 975) among nonattenders and 88.9% (773 of 870) among attenders. Adjusting for screening arm, center, gender, age, and education, participation was significantly higher among people who consulted their GP before undergoing screening (OR: 4.24; 95% confidence interval (CI): 3.11-5.78), who mentioned one first-degree relative with CRC (OR: 3.62; 95% CI: 2.02-6.49), who reported regular physical activity (OR: 1.85; 95% CI: 1.33-2.55), and who read the mailed information (letter only: OR: 1.85; 95% CI: 1.23-2.78; letter+leaflet: OR: 3.18; 95% CI: 2.12-4.76). People who considered screening to be ineffective (OR: 0.12; 95% CI: 0.08-0.19), those who considered it to be effective but reported even moderate levels of anxiety (OR: 0.32; 95% CI: 0.23-0.45), and those who mentioned previous knowledge of CRC screening tests were less likely to accept the invitation (OR: 0.49; 95% CI: 0.34-0.70).
CONCLUSIONS: Adoption of health protective behaviors is associated with a higher attendance rate, whereas anxiety represents a strong barrier, even among people who deemed screening to be effective. Increasing the proportion of people who consult their GP when making a decision regarding screening might enhance participation.