rubrica

Screening

  • Paolo Giorgi Rossi1

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

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Ricerca bibliografica periodo 1 febbraio 2011 – 1 aprile 2011

Per leggere le caratteristiche di questa ROUTINE di ricerca clicca qui

Database: Pubmed/MEDline
Stringa:
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

Commento generale a cura di Paolo Giorgi Rossi
In soli 60 giorni sono usciti 20 lavori prodotti da gruppi italiani sugli screening. Oltre alla quantità stupisce anche il livello delle riviste, una lettera sul New England Journal of Medicine e un articolo su PNAS solo per citarne due. Un grosso contributo è venuto dalla ricerca clinica e genetica con lavori che partono dalla caratterizzazione dei casi screen detected per individuare marcatori prognostici o dall’individuazione di mutazioni nelle linee germinali per proporre screening dei familiari a rischio. Proprio la ricerca sugli screening genetici o la medicina predittiva ha visto in questi 60 giorni diversi lavori pubblicati per diverse patologie oncologiche (colon retto, polmone, mammella, tiroide).
Gli screening più trattati sono quelli del colon retto (5 lavori) e della cervice con due lavori sul self-sampling, due sulla prevalenza di HPV e uno di validazione di un nuovo test per lo screening coon HPV, seguiti da mammella e polmone (4 lavori ciascuno). Compaiono due lavori uno sulla tiroide e uno sul cancro orale, due patologie per le quali l’opportunità di uno screening non è assolutamente dimostrata, ma già si propongono e si valutano test. Un solo lavoro su di uno screening neonatale: l’ipotiroidismo.

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

1. Caumo F, Brunelli S, Zorzi M, Baglio I, Ciatto S, Montemezzi S. Benefits of double reading of screening mammograms: retrospective study on a consecutive series. Radiol Med. 2011 Mar 7. [Epub ahead of print]
PO Marzana, ULSS 20, Centro di Prevenzione Senologica (CPS), Piazza L. Lambranzi 1, 37142, Verona, Italy.

Abstract
PURPOSE: The purpose of this study was to assess the performance of delayed second reading of screening mammograms when added to real-time reading plus immediate assessment.
MATERIAL AND METHODS: The study setting was the mammography screening programme of an Italian Local Health Unit. Recall rate and cancer detection rate at first reading or informed second reading only were assessed in a cohort of 23,629 women aged 50-69 years screened during 2007-2008. Incremental recall rate, incremental cancer detection rate and incremental cost of second reading were determined.
RESULTS: Recall rate was 13.0% at first and 2.7% at second reading (incremental recall rate +21.1%). Overall, recalls were more frequent in the younger decade and in the presence of denser breasts. Cancer detection rate was 7.06‰ (n=167) at first and 0.93‰ (n=22) at second reading (incremental cancer detection rate +13.1%). Compared with first reading, second reading detected more cancers depicted as isolated microcalcifications and distortions (40.9% vs. 16.2%, p=0.02) and at a lower stage (stage 0-I 81.8% vs. 69.5%, p=0.34). The cost of adding delayed second reading was + 3.65 per screened individual or 3,926.61 per incremental cancer detected.
CONCLUSIONS: The study confirms the efficacy of second reading, even as an adjunct to real-time single reading plus immediate assessment. Incremental recall rate is acceptable in view of the incremental cancer detection rate, and both figures are within the range of literature reports on double-reading performance.

2. Sideri M, Igidbashian S, Boveri S, Radice D, Casadio C, Spolti N, Sandri MT. Age distribution of HPV genotypes in cervical intraepithelial neoplasia. Gynecol Oncol. 2011 Mar 10. [Epub ahead of print]
Preventive Gynaecology Unit, European Institute of Oncology, via Ripamonti 435, 20141 Milan, Italy.

Abstract
OBJECTIVE: Recent data showed that HPV16 infections in young women can lead to CIN3 formation very quickly and questioned the common assumption that invasive cervical cancer develops through slowly progressing pre-cancer lesions, CIN1, CIN2 and CIN3. The aim of the study is to compare the age distribution of HPV 16/18 related and HPV16/18 not related CIN.
METHODS: We used the data generated from the clinical use of HPV genotyping (LINEAR ARRAY, Roche Diagnostics). Patients were grouped on the basis of histology, CIN1 vs. CIN2+ and on HR-HPV genotype status.
RESULTS: The probability to develop a CIN2+ seemed to decrease with age in patients infected with HR-HPV genotype 16/18 while the inverse effect was observed in CIN2+ patients who were HR-HPV positive but HPV16/18 negative (Chi-square test, p(trend)=0.01). Only in HR-HPV positive but HPV 16/18 negative patients, a relative reduction of CIN1 vs. CIN2+ was observed with increasing age (Cochran-Armitage test, p(trend)=0.01); finally, in HR-HPV non-16/18 infected patients only a statistically significant difference in mean age between CIN1 and CIN2+ patients below age 35 was observed.
CONCLUSIONS: Besides the limitations of the present cross-sectional analysis, these data suggest a genotype specific natural history of cervical cancer precursors development: one type, more frequent, HPV16/18 related, which develops quick and early in life; another one, non-16/18 HR-HPV related, which develops later, slowly, through low- to high-grade lesions. If confirmed, this hypothesis could influence screening policies, especially in the vaccinated population.

3. Mandelli G, Radaelli F, Paggi S, Terreni N, Gola G, Gramegna M, Bonaffini A, Terruzzi V. Anticoagulant or aspirin treatment does not affect the positive predictive value of an immunological fecal occult blood test in patients undergoing colorectal cancer screening: results from a nested in a cohort case-control study. Eur J Gastroenterol Hepatol. 2011 Apr;23(4):323-6.
Gastroenterology Unit, Valduce Hospital bAzienda Sanitaria Locale, Como, Italy.

Abstract
BACKGROUND AND AIM: The immunochemical fecal occult blood test (i-FOBT) is widely used as a recommended screening strategy for colorectal cancer (CRC). A growing number of patients potentially targeted by CRC screening programs are on oral anticoagulant or chronic low-dose aspirin therapy, mainly for primary or secondary cardiovascular prophylaxis. This study aims at evaluating whether the use of these medications may impact on the diagnostic performances of i-FOBT for CRC screening.
METHODS: All i-FOBT-positive patients on anticoagulant or chronic low-dose aspirin therapy recorded in a regional mass screening program database were enrolled as cases. Control groups were derived from the same database and included drug-naive i-FOBT-positive patients, matched in a ratio of 1 : 2 for age (±3 years of age), sex, date of colonoscopy, and practice site. Information about the use of medications was collected by cross-checking patients' interview before colonoscopy and data recorded in the provincial electronic registry of medical prescriptions. The positive predictive value of i-FOBT for significant neoplasia (high-risk adenoma and CRC) was calculated in the case and control groups.
RESULTS: In a 2-year study period, 2376 patients were recorded in the regional database. Of these patients, 53 (2%) were on anticoagulation (control group of 106 patients) and 172 (6.6%) were on chronic low-dose aspirin treatment (control group of 344 patients). Significant neoplasia was detected in 15 (28.3%) patients on anticoagulants and in 37 (34.9%) corresponding controls (P=0.45). Significant neoplasia was detected in 50 (29.1%) patients on chronic low-dose aspirin and in 107 (31.1%) corresponding controls (P=0.64).
CONCLUSION: The positive predictive value of i-FOBT for significant neoplasia is not affected by ongoing anticoagulant or chronic low-dose aspirin therapy. This finding suggests that there is no need to interrupt these treatments before i-FOBT for CRC screening.

4. Flor N, Rigamonti P, Di Leo G, Ceretti AP, Opocher E, Sardanelli F, Cornalba GP. Technical quality of CT colonography in relation with diverticular disease. Eur J Radiol. 2011 Feb 25. [Epub ahead of print]
Dipartimento di Scienze Medico-Chirurgiche, Università degli Studi di Milano, Milan, Italy; Unità Operativa di Radiologia Diagnostica e Interventistica, Azienda Ospedaliera San Paolo, Milan, Italy.

Abstract
OBJECTIVE: The aim of the study is to explore how the technical quality of the examination was affected by diverticular disease.
MATERIALS AND METHODS: We retrospectively evaluated a consecutive series of 78 subjects who underwent CTC for screening (n=58) or staging (n=20) colorectal cancer, 38 of them (49%) after an incomplete optical colonoscopy. Patients were administered a mild laxative and a iodinated contrast material for fecal tagging. We scored both the bowel preparation and the overall colon distension as poor, good, or optimal and measured the mean sigmoid colon diameter. We counted the number of diverticula and classified patients as having or not a severe diverticular disease (SDD). The number of the prompts of computer aided diagnosis (CAD) per patient was also considered. Mann-Whitney U and χ(2) tests were performed.
RESULTS: No CTC complications occurred. The bowel cleansing was poor in 8 (10%) patients, good in 29 (37%) and optimal in 41 (53%); colon distension was poor in 7 (9%) patients, good in 38 (49%), and optimal in 33 (42%). Fifty-four (69%) showed diverticula and 30 (38%) had an SDD. Bowel cleansing and distension were not significantly impaired by neither diverticula (p>0.590) nor the SDD (p>0.110). Mean sigmoid colon diameter was reduced in presence of diverticula (28mm versus 23mm, p=0.009) or SDD (26mm versus 22mm, p=0.016). The mean number of CAD prompts per patient was not significantly increased by the presence of SDD (p=0.829).
CONCLUSIONS: Bowel cleansing and distension at CTC were not influenced by the presence of diverticular disease.

5. Armelao F, Paternolli C, Franceschini G, Franch R, Orlandi PG, Miori G, Avancini I, Togni M, Rossi M, Meggio A, Tasini E, Manfrini R, Giacomin D, Fasoli R, Faitini K, Mastromauro M, Costa S, Ridolfi F, Rosi P, de Pretis G. Colonoscopic findings in first-degree relatives of patients with colorectal cancer: a population-based screening program. Gastrointest Endosc. 2011 Mar;73(3):527-534.e2.
Department of Gastroenterology, Ospedale Santa Chiara, APSS, Trento, Italy. franco.armelao@apss.tn.it

Abstract
BACKGROUND: A screening colonoscopy is recommended in first-degree relatives (FDRs) of colorectal cancer patients; few prospective, controlled studies have evaluated colorectal findings in a population-based screening program.
OBJECTIVE: To evaluate the prevalence of colorectal neoplasia (adenomas and adenocarcinomas) in this increased-risk population, to compare it with that of average-risk individuals, and to identify features that might allow risk stratification for neoplasia among FDRs. DESIGN: Cross-sectional study.
SETTING: Population-based screening program in Trentino, Italy.
PATIENTS: FDRs of colorectal cancer patients between 45 and 75 years of age with no history of hereditary colorectal cancer syndromes or inflammatory bowel disease.
CONTROLS: Average-risk individuals undergoing screening colonoscopy.
INTERVENTION: Screening colonoscopy.
RESULTS: Neoplasia was found in 33.4% of 1252 FDRs and in 30.3% of 765 controls; advanced neoplasia was found in 11.3% of FDRs and in 6.3% of controls. Odds ratios (ORs) from the multivariate logistic regression analysis adjusted for age, sex, cecal intubation rates, and colon cleansing showed an increased risk of advanced neoplasia (OR 2.41; 95% CI, 1.69-3.43; P < .0001) in FDRs. Age older than 56 years (OR 1.83; 95% CI, 1.15-2.99; P = .013) and male sex (OR 2.17; 95% CI, 1.39-3.10; P < .001) are independent predictors of advanced neoplasia.
LIMITATIONS: Italian subjects living in the same geographic area; of 4301 FDRs, 2521 were excluded.
CONCLUSIONS: The increased risk of advanced neoplasia supports the current recommendation for colonoscopic screening in this group; age and sex may assist in risk stratification of these individuals.

6. Igidbashian S, Boveri S, Spolti N, Radice D, Sandri MT, Sideri M. Self-collected human papillomavirus testing acceptability: comparison of two self-sampling modalities. J Womens Health (Larchmt). 2011 Mar;20(3):397-402. Epub 2011 Feb 25.
Preventive Gynaecology Unit, European Institute of Oncology , Milan, Italy .

Abstract
Background: Human papillomavirus (HPV) testing can be used as a primary test for cervical cancer screening. HPV self-sampling has the potential to replace physician/nurse sampling. Our objective was to compare the acceptability of two self-sampling methods among 205 women undergoing an excisional procedure for cervical intraepithelial neoplasia (CIN) at the European Institute of Oncology (IEO).
Methods: One hundred eleven patients were given a Hybrid Capture (HC) Cervical Sampler™ (Qiagen, Hilden, Germany), and 94 received a self-lavaging device, the Delphi(®) Screener (Delphi Bioscience, Scherpenzeel, The Netherlands), both with written instructions. Self-sampling was performed just before the clinician-collected cervical sample. Women responded to questions using 5-point ordinal scales on the general acceptability of self-sampling and the physical comfort, embarrassment, pain, and difficulty experienced. Participants were also asked whether they prefer self-sampling or clinician sampling.
Results: Both self-sampling methods were generally accepted with a significantly high score (p = 0.005) and significantly lower embarrassment (p = 0.042) in favor of the Delphi Screener. Both self-sampling methods were physically well accepted, not painful, and easy to perform. Most women (n = 117, 68%) preferred the self-sampled compared to the clinician-sampled test, with a significantly higher proportion in the Delphi Screener group (n = 59, 77.6%) compared to those using the HC Sampler (n = 58, 60.4%) (p = 0.021).
Conclusions: The present study shows that self-sampling for HPV testing is favorably received by women. A sampling device specifically developed for self-sampling, such as the Delphi Screener, shows the highest degree of satisfaction. A well-accepted HPV sampling method could be especially useful for women who do not take part in cervical screening or in settings where organized screening is not fully implemented.

7. Grazzini G, Zappa M, Halloran SP. Limited effect of summer warming on the sensitivity of colorectal cancer screening. Gut. 2011 Feb 16. [Epub ahead of print]
Cancer Prevention and Research Institute (ISPO), Florence, Italy.
8. Carozzi FM, Burroni E, Bisanzi S, Puliti D, Confortini M, Giorgi Rossi P, Sani C, Scalisi A, Chini F. Comparison of clinical performance of Abbott RealTime High Risk HPV test with Hybrid Capture(R) 2 Assay in a screening setting. J Clin Microbiol. 2011 Feb 16. [Epub ahead of print]
ISPO, Cancer Prevention and Research Institute, Florence, Italy; Laziosanità, Rome, Italy; ASL Catania, Italy.

Abstract
Randomised trials have produced sound evidence about the efficacy of screening with HPV DNA tests in reducing cervical cancer incidence and mortality. We evaluated the clinical performance and the reproducibility of the Abbott RealTime HR HPV test compared with that of the HR HC2 assay assessed by non-inferiority score test. A random sample of 998 cervical specimens (914

9. Boeri M, Verri C, Conte D, Roz L, Modena P, Facchinetti F, Calabrò E, Croce CM, Pastorino U, Sozzi G. MicroRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer. Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3713-8. Epub 2011 Feb 7.
Tumor Genomics Unit, Department of Experimental Oncology and Molecular Medicine, and Unit of Thoracic Surgery, Fondazione IRCCS Istituto Nazionale Tumori, 20133 Milan, Italy.

Abstract
The efficacy of computed tomography (CT) screening for early lung cancer detection in heavy smokers is currently being tested by a number of randomized trials. Critical issues remain the frequency of unnecessary treatments and impact on mortality, indicating the need for biomarkers of aggressive disease. We explored microRNA (miRNA) expression profiles of lung tumors, normal lung tissues and plasma samples from cases with variable prognosis identified in a completed spiral-CT screening trial with extensive follow-up. miRNA expression patterns significantly distinguished: (i) tumors from normal lung tissues, (ii) tumor histology and growth rate, (iii) clinical outcome, and (iv) year of lung cancer CT detection. Interestingly, miRNA profiles in normal lung tissues also displayed remarkable associations with clinical features, suggesting the influence of a permissive microenvironment for tumor development. miRNA expression analyses in plasma samples collected 1-2 y before the onset of disease, at the time of CT detection and in disease-free smokers enrolled in the screening trial, resulted in the generation of miRNA signatures with strong predictive, diagnostic, and prognostic potential (area under the ROC curve ≥ 0.85). These signatures were validated in an independent cohort from a second randomized spiral-CT trial. These results indicate a role for miRNAs in lung tissues and plasma as molecular predictors of lung cancer development and aggressiveness and have theoretical and clinical implication for lung cancer management.

10. Veronesi G, Maisonneuve P, Pelosi G, Casiraghi M, Agoglia BG, Borri A, Travaini LL, Bellomi M, Rampinelli C, Brambilla D, Bertolotti R, Spaggiari L. Screening-detected lung cancers: is systematic nodal dissection always essential? J Thorac Oncol. 2011 Mar;6(3):525-30.
Division of Thoracic Surgery, European Institute of Oncology, Milan, Italy.

Abstract
BACKGROUND: To address whether systematic lymph node dissection is always necessary in early lung cancer, we identified factors predicting nodal involvement in a screening series and applied them to nonscreening-detected cancers.
METHODS: In the 97 patients with clinical T1-2N0M0 lung cancer (<3 cm), enrolled in the Continuous Observation of Smoking Subjects computed tomography (CT) screening study, who underwent curative resection with radical mediastinal lymph node dissection, we examined factors associated with hilar extrapulmonary and mediastinal nodal involvement. Nodule size plus positive/negative positron emission tomography (PET)-CT (usually as maximum standard uptake value [maxSUV]) were subsequently evaluated retrospectively for their ability to predict nodal involvement in 193 consecutive patients with nonscreening-detected clinical stage I lung cancer.
RESULTS: Among Continuous Observation of Smoking Subjects patients, 91 (94%) were pN0, and six (6.2%) were pN+. All patients with maxSUV <2.0 (p = 0.08) or pathological nodule ≤10 mm (p = 0.027) were pN0 (62 cases). Nodal metastases occurred in 6 cases among the 29 (17%) patients with lung nodule >10 mm and maxSUV ≥2.0 (p = 0.002 versus the other 62 cases). In the nonscreening series, 42 of 43 cases with negative PET-CT (usually maxSUV <2.0) or nodule ≤10 mm were pN0; 33 of 149 (22%) cases with positive PET-CT (usually maxSUV ≥ 2.0) and nodule >10 mm were pN+ (p = 0.001 versus the 43 cases).
CONCLUSIONS: This limited experience suggests that in early-stage clinically N0 lung cancers with maxSUV <2.0 or pathological nodule size ≤10 mm, systematic nodal dissection can be avoided as the risk of nodal involvement is very low.

11. Lastella P, Patruno M, Forte G, Montanaro A, Di Gregorio C, Sabbà C, Suppressa P, Piepoli A, Panza A, Andriulli A, Resta N, Stella A. Identification and surveillance of 19 Lynch syndrome families in southern Italy: report of six novel germline mutations and a common founder mutation. Fam Cancer. 2011 Feb 1. [Epub ahead of print]
UOC Genetica Medica-Dipartimento di Biomedicina dell'Età Evolutiva-Università di Bari "Aldo Moro" Azienda, Ospedaliero-Universitaria Policlinico P.zza G. Cesare 11, 70124, Bari, Italy.

Abstract
Lynch syndrome (LS), or hereditary non-polyposis colorectal cancer (HNPCC), is an autosomal dominant condition responsible for early onset cancer mostly in the colonrectum and endometrium as well as in other organ sites. Lynch syndrome is caused by germline mutations in mismatch repair genes, prevalently in hMSH2, hMLH1, and less frequently in hMSH6 and hPMS2. Twenty-nine non-related index cases with colorectal cancer (CRC) were collected from a region in southeast Italy (Apulia). Among this set of patients, fifteen fulfilled the Amsterdam criteria II. The presence of tumor microsatellite instability (MSI) was assessed in all index cases and 19 (15 AC+/4 AC-) were classified as MSI-H. Mutation analysis performed on all patients, identified 15 pathogenic mutations in hMLH1 and 4 in hMSH2. 4/15 mutations in hMLH1 and 2/4 hMSH2 mutations have not been previously reported. Three previously reported mutations were further investigated for the possibility of a common founder effect. Genetic counseling was offered to all probands and extended to 183 relatives after molecular testing and 85 (46%) mutation carriers were identified. Eighty mutation carriers underwent an accurate clinical and instrumental surveillance protocol. Our results confirm that the identification of LS patients based exclusively on family history may miss patients carrying germline mutations in the MMR genes. Moreover, our results demonstrated that molecular screening and subsequent instrumental surveillance are very effective in identifying CRCs at earlier stages and reducing the number of deaths from secondary cancers in HNPCC patients.

12. Navone R, Pentenero M, Gandolfo S. Liquid-based cytology in oral cavity squamous cell cancer. Curr Opin Otolaryngol Head Neck Surg. 2011 Jan 19. [Epub ahead of print]
Department of Biomedical Sciences and Human Oncology of the University of Turin, Pathology Section, Italy bDepartment of Clinical and Biological Sciences of the University of Turin, Oral Medicine and Oral Oncology Section, Regione Gonzole, Orbassano, Torino, Italy.

Abstract
PURPOSE OF REVIEW: Oral exfoliative cytology is a practical tool for early diagnosis of squamous cell carcinoma (OSCC) and potentially malignant lesion (OPML), but is not yet extensively used. A literature review evaluated conventional and liquid-based oral diagnostic cytology efficacy and efficiency. 'Special' techniques like liquid-based cytology, computer-assisted cytology, Oral CDx, DNA ploidy, immunocytochemistry, molecular analyses and microhistology were reviewed.
RECENT FINDINGS: Cytology was useful when diagnosing OSCC and OPML. Oral CDx may assess dysplastic changes in clinically suspicious (class I) lesions, with doubtful efficacy in apparently innocuous (class II) lesions. Flow and/or image cytometry and immunocytochemistry can identify markers for the prediction of evolution of the OPML to OSCC. Molecular biology can detect the minimal residual clonal population of cancer cells in field cancerization and oral mucosa surgical margins. Microhistology is a reliable first level test in class II lesions for selected cases requiring surgical biopsy.
SUMMARY: Conventional cytology helps in OSCC and OPML screening; liquid-based cytology gives better results, enhancing both sensitivity and specificity, and provides material for further investigation. Sampling with the 'curette technique' permits collection of 'accidental' tissue fragments used as microbiopsies and proved a useful first-level test for the management of class II OPML.

13. Giorgi Rossi P, Chini F, Bisanzi S, Burroni E, Carillo G, Lattanzi A, Angeloni C, Scalisi A, Macis R, Pini MT, Capparucci P, Guasticchi G, Carozzi FM; the Prevalence Italian Working Group.HPV. Distribution of high and low risk HPV types by cytological status: a population based study from Italy. Infect Agent Cancer. 2011 Jan 20;6(1):2.
Laziosanità - Agency for Public Health, Lazio Region, Via di S, Costanza 53, 00198 - Rome, Italy. giorgirossi@asplazio.it.

Abstract
BACKGROUND: HPV type distribution by cytological status represents useful information to predict the impact of mass vaccination on screening programs.
METHODS: women aged from 25 to 64 who attended cervical cancer screening in five different Italian regions were tested for HPV infection with Hybrid Capture II (HCII) low and high risk probes. Women repeating Pap-test upon unsatisfactory or positive results, or as a post-treatment and post-colposcopy follow-up analysis, were excluded from our study. High risk (HR) HPV positive samples were typed using GP5+/GP6+ primed PCR, followed by Reverse Line Blot for 18 high/intermediate risk HPV types, while low risk (LR) HPV positive samples were tested with type specific primers for HPV6 and HPV11
RESULTS: 3410 women had a valid HCII and Pap-test. The prevalence of HR and LR infections was 7.0% and 3.6%, 29.1% and 13.7%, 68.1% and 31.9%, 60.0% and 0.0%, 65.0% and 12.0%, for negative, ASC-US, L-SIL, ASC-H and H-SIL cytology, respectively. The fraction of ASC-US+ cytology due to HPV 16 and 18 ranged from 11.2 (HPV 16/18 alone) to 15.4% (including HPV 16/18 in co-infection with other virus strains), and that due to HPV 6 and 11 ranged from 0.2% (HPV 6/11 alone) to 0.7% (including HPV 6/11 in co-infection with other LR virus strains).
CONCLUSIONS: mass vaccination with bivalent or quadrivalent HPV vaccine would modestly impact on prevalence of abnormal Pap-test in screening.

14. Puliti D, Miccinesi G, Zappa M. More on screening mammography. N Engl J Med. 2011 Jan 20;364(3):284-5; author reply 286.
Comment on: N Engl J Med. 2010 Sep 23;363(13):1276-8.
15. Sardanelli F, Podo F, Santoro F, Manoukian S, Bergonzi S, Trecate G, Vergnaghi D, Federico M, Cortesi L, Corcione S, Morassut S, Di Maggio C, Cilotti A, Martincich L, Calabrese M, Zuiani C, Preda L, Bonanni B, Carbonaro LA, Contegiacomo A, Panizza P, Di Cesare E, Savarese A, Crecco M, Turchetti D, Tonutti M, Belli P, Maschio AD; High Breast Cancer Risk Italian 1 (HIBCRIT-1) Study. Multicenter surveillance of women at high genetic breast cancer risk using mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (the high breast cancer risk italian 1 study): final results. Invest Radiol. 2011 Feb;46(2):94-105.
Dipartimento di Scienze Medico-Chirurgiche, Università degli Studi di Milano, IRCCS Policlinico San Donato, Unità di Radiologia, San Donato Milanese, Milano, Italy. f.sardanelli@grupposandonato.it

Abstract
OBJECTIVES: To prospectively compare clinical breast examination, mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (MRI) in a multicenter surveillance of high-risk women.
MATERIALS AND METHODS: We enrolled asymptomatic women aged ≥ 25: BRCA mutation carriers; first-degree relatives of BRCA mutation carriers, and women with strong family history of breast/ovarian cancer, including those with previous personal breast cancer.
RESULTS: A total of 18 centers enrolled 501 women and performed 1592 rounds (3.2 rounds/woman). Forty-nine screen-detected and 3 interval cancers were diagnosed: 44 invasive, 8 ductal carcinoma in situ; only 4 pT2 stage; 32 G3 grade. Of 39 patients explored for nodal status, 28 (72%) were negative. Incidence per year-woman resulted 3.3% overall, 2.1% <50, and 5.4% ≥ 50 years (P < 0.001), 4.3% in women with previous personal breast cancer and 2.5% in those without (P = 0.045). MRI was more sensitive (91%) than clinical breast examination (18%), mammography (50%), ultrasonography (52%), or mammography plus ultrasonography (63%) (P < 0.001). Specificity ranged 96% to 99%, positive predictive value 53% to 71%, positive likelihood ratio 24 to 52 (P not significant). MRI showed significantly better negative predictive value (99.6) and negative likelihood ratio (0.09) than those of the other modalities. At receiver operating characteristic analysis, the area under the curve of MRI (0.97) was significantly higher than that of mammography (0.83) or ultrasonography (0.82) and not significantly increased when MRI was combined with mammography and/or ultrasonography. Of 52 cancers, 16 (31%) were diagnosed only by MRI, 8 of 21 (38%) in women <50, and 8 of 31 (26%) in women ≥ 50 years of age.
CONCLUSION: MRI largely outperformed mammography, ultrasonography, and their combination for screening high-risk women below and over 50.

16. Bisacchi N, Bal MO, Nardi L, Bettocchi I, D'Addabbo G, Conti V, Monti S, D'Alberton F, Cicognani A, Cassio A. Psychological and behavioural aspects in children and adolescents with congenital hypothyroidism diagnosed by neonatal screening: comparison between parents' and children's perceptions. Eur J Endocrinol. 2011 Feb;164(2):269-76. Epub 2010 Nov 23.
Department of Gynaecologic, Obstetric and Paediatric Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.

Abstract
OBJECTIVE: To compare the psychological adjustment and behaviour of congenital hypothyroidism (CH) children and their parents with a control group.
STUDY DESIGN: A cross-sectional study was carried out with 84 CH subjects diagnosed by neonatal screening (range 2.7-18.6 years), subdivided into four age groups: group 1 (2-5 years); group 2 (6-10 years); group 3 (11-13 years); and group 4 (14-18 years) and was compared with an age-matched control group. Patients were assessed using two questionnaires: Child Behaviour Checklist for parents and Youth Self-Report for children over 11 years of age.
RESULTS: In groups 1, 3 and 4, total score (TS), internalising score (IS=problems within the self) and externalising score (ES=conflicts with other people) as reported by parents were not significantly different in CH patients and in controls. In group 2, parents of CH children showed values of TS (P<0.05), IS (P<0.05), ES (P<0.05) and scores on other scales significantly higher than controls. In self-reports of groups 3 and 4, the behavioural scales were not significantly different in CH patients and in controls.
CONCLUSIONS: Paediatricians should be informed about the increased risk of the development of behavioural problems at primary school age in CH patients. At this age special attention should be paid to parental worries and anxiety. However, it can be reassuring for the patients and parents to know that the problems may be related to CH, and that they may spontaneously disappear.

17. Romei C, Cosci B, Renzini G, Bottici V, Molinaro E, Agate L, Passannanti P, Viola D, Biagini A, Basolo F, Ugolini C, Materazzi G, Pinchera A, Vitti P, Elisei R. RET genetic screening of sporadic medullary thyroid cancer (MTC) allows the preclinical diagnosis of unsuspected gene carriers and the identification of a relevant percentage of hidden familial MTC (FMTC). Clin Endocrinol (Oxf). 2011 Feb;74(2):241-7. doi: 10.1111/j.1365-2265.2010.03900.x.
Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy. Comment in: Nat Rev Endocrinol. 2011 Feb;7(2):63.

Abstract
OBJECTIVE: This study was aimed to demonstrate the clinical benefits of rearranged during transfection (RET) genetic screening in patients with apparently sporadic medullary thyroid cancer (MTC) not only to identify the hereditary nature of the disease in the index case but also to discover family members harbouring the same germline mutations (i.e. gene carriers) who are unaware of their condition.
CONTEXT: RET genetic screening allowed the identification of germline RET mutations in apparently sporadic MTC resulting in their re-classification as hereditary forms. PATIENTS AND
MEASUREMENTS: RET genetic screening was performed in 729 apparently sporadic MTC patients by direct sequencing RET exons 5, 8, 10, 11 and 13-16. Clinical and biochemical evaluation of gene carriers was also performed.
RESULTS: We discovered an unsuspected germline RET mutation in 47 of 729 (6•5%) apparently sporadic MTC who were re-classified as hereditary. We found 60 of 146 (41•1%) gene carriers, 35 of whom had biochemical or clinical evidence of MTC. Thirty gene carriers underwent total thyroidectomy and 27 of 30 (90%) were persistently cured after a mean follow-up of 6•0 years. As a further result of RET genetic screening, we observed a significantly higher prevalence of familial medullary thyroid cancer (FMTC) in our series with respect to the largest series of the International RET Consortium (P = 0•0002).
CONCLUSIONS: RET genetic screening of patients with apparently sporadic MTC represents a major tool for the preclinical diagnosis and early treatment of unsuspected affected family members and allows the identification of a relevant percentage of hidden FMTC.

18. Belloni E, Veronesi G, Micucci C, Javan S, Minardi SP, Venturini E, Maisonneuve P, Volorio S, Riboni M, Bellomi M, Scanagatta P, Taliento G, Pelosi G, Pece S, Spaggiari L, Pelicci PG. Genomic characterization of asymptomatic CT-detected lung cancers. Oncogene. 2011 Mar 3;30(9):1117-26. Epub 2010 Oct 25.
[1] Department of Experimental Oncology, European Institute of Oncology, Milan, Italy [2] IFOM-IEO Campus, Milan, Italy.

Abstract
Computed tomography (CT) screening of lung cancer allows the detection of early tumors. The objective of our study was to verify whether initial asymptomatic lung cancers, identified by high-resolution low-dose CT (LD-CT) on a high-risk population, show genetic abnormalities that could be indicative of the early events of lung carcinogenesis. We analyzed 78 tumor samples: 21 (pilot population) from heavy smokers with asymptomatic non-screening detected early-stage lung cancers and 57 from 5203 asymptomatic heavy smoker volunteers, who underwent a LD-CT screening study. During surgical resection of the detected tumors, tissue samples were collected and short-term cultures were started for karyotype evaluation. Samples were classified according to the normal (NK) or aneuploid (AK) karyotype. The NK samples were further analyzed by the Affymetrix single-nucleotide polymorphisms (SNPs) technology. Metaphase spreads were obtained in 73.0% of the selected samples: 80.7% showed an AK. A statistically significant correlation was found between presence of vascular invasion and abnormal karyotype. A total of 10 NK samples were suitable for SNPs analysis. Subtle genomic alterations were found in eight tumors, the remaining two showing no evidence to date of chromosomal aberrations anywhere in the genome. Two common regions of amplification were identified at 5p and 8p11. Mutation analysis by direct sequencing was conducted for the K-RAS, TP53 and EGFR genes, confirming data already described for heavy smokers. We show that: (i) the majority of screening-detected tumors are aneuploid; (ii) early-stage tumors tend to harbor a less abnormal karyotype; (iii) whole genome analysis of NK tumors allows for the detection of common regions of copy number variation (such as amplifications at 5p and 8p11), highlighting genes that might be considered candidate markers of early events in lung carcinogenesis.

19. Knox S. The European advocacy perspective on mammography screening. Breast. 2011 Feb;20(1):93-5. Epub 2010 Aug 12.
EUROPA DONNA-The European Breast Cancer Coalition, Head Office, Piazza Amendola 3, Milan, Italy. susan.knox@europadonna.org

Abstract
Controversy and publicity about the value of mammography screening programs continue in Europe and across the globe. As Europe's breast cancer advocacy organisation, Europa Donna-The European Breast Cancer Coalition advocates for mammography screening as one of the essential services to which all women should have access, stipulating, however, that mammography screening programs must be set up and carried out in accordance with the European Guidelines for quality assurance in breast cancer screening and diagnosis. Europa Donna's involvement and history in following programs and progress in this area is extensive and dates back to 2001. The communication process for women eligible for screening is complicated and needs to be addressed appropriately in every country. However, the position of our organisation remains unchanged: Mammography screening carried out according to EU Guidelines is the best form of early detection available today and the scientific evidence shows that it improves mortality rates from the disease.

20. Bettio D, Venci A, Cariboni U, Di Rocco M, Infante M. Fluorescent in situ hybridization (FISH) in the differential diagnosis of ground-glass opacities in the lung. Lung Cancer. 2011 Mar;71(3):319-22. Epub 2010 Jul 31.
Cytogenetic Laboratory, Operative Unit of Clinical Investigations, IRCCS Humanitas Clinical Institute, Milan 20089, Italy. daniela.bettio@humanitas.it

Abstract
Computed tomographic (CT) screening for lung cancer has increased the detection rate of nodules manifesting as ground-glass opacities (GGOs). The natural history of this new entity it is not well known nor is the factors that influence the growth, progression and malignant potential. This genetic study was performed in order to identify molecular markers with possible diagnostic and prognostic significance to differentiate lesions with malignant or benign profiles. Ten pure GGO fresh samples and 5 specimens of normal lung tissue were cytogenetically investigated using a direct method and short-term cultures, and molecular analysis was performed using the 4-target FISH LAVysion kit for the detection of non-small cell lung cancer (NSCLC). Interestingly, all the karyotypes turned out to be normal both with the direct method and cultured cells, while in 3 out of 10 GGOs FISH analysis was abnormal for all the targets and in 2 cases only c-MYC amplification was observed. Karyotypes and FISH performed on the normal tissue samples gave normal results. Two of three FISH positive patients died, one had a relapse of the disease and at the last follow-up showed lung and bone metastases. Despite the small sample due to the rarity of pure GGOs, these preliminary results indicate that interphase FISH analyses are more informative than metaphase studies and might contribute clinically relevant information about the nature of these lesions. PMID: 20674071 [PubMed - in process]