rubrica

Screening

  • Paolo Giorgi Rossi1

  1. Servizio interaziendale di epidemiologia, AUSL Reggio Emilia

Ricerca bibliografica periodo dal 1 aprile 2013 al 15 giugno 2013

Per leggere le caratteristiche di questa ROUTINE di ricerca clicca qui

Stringa: ("mass screening"[MeSH Terms] OR cancer[Title/Abstract] AND screening[Title/Abstract] AND ("italy"[MeSH Terms] OR "italy"[All Fields]) AND ("2013/04/01"[PDAT] : "2013/06/15"[PDAT])

Breve commento a cura di P. Giorgi Rossi
In questi due mesi e mezzo sono usciti ben 15 lavori prodotti da gruppi italiani sullo screening, molti su riviste ad alto impact factor, primo fra tutti il lavoro dello studio STORM, su Lancet Oncology, sull’uso della tomosintesi nello screening mammografico: ancora un’eredità di un grande medico e ricercatore italiano scomparso poco più di un anno fa, Stefano Ciatto. La scomparsa di Stefano ha lasciato un vuoto incolmabile in tutti noi che lo conoscevamo ed ora quando ci confrontiamo con la sua monumentale produzione scientifica dobbiamo pensare a come faremo a proseguire senza di lui. Anche in questa edizione, come già altre volte, troviamo lavori di ricerca di base o traslazionale che prendono la loro casistica dai trial in corso sullo screening del polmone (Infante, Terzi, D’Urso, Gnagnarella). È uscito il primo lavoro del progetto IMPATTO cervice (Zucchetto), cui auguriamo una evoluzione altrettanto proficua del suo cugino maggiore IMPATTO mammella, presente con un lavoro anche questo (Foca). Sono uscite anche delle revisioni sistematiche (Hassan; Camilloni) e non (Pastorino) e alcuni lavori che presentano risultati importanti di esperienze pilota (Sassoli de’ Bianchi, Venturini). Fra questi vorrei però puntare l’attenzione su di un lavoro sulla diagnosi precoce dei noduli tiroidei: Gnarini e colleghi trovano un’altissima prevalenza di noduli maligni nella popolazione sana, 1%, ma concludono “US screening not necessarily results in the over-diagnosis of clinically not relevant thyroid diseases”; per un tumore che ha una mortalità prossima allo zero, direi che una detection rate dell’1% in soggetti con età media 46 anni sia una prova evidente di sovradiagnosi. Siamo già in presenza di una enorme epidemia di tumore della tiroide nei paesi industrializzati; non conosciamo tutte le cause di questa epidemia e forse sono diverse in diversi paesi, ma su di una cosa tutti gli studi convergono: un ruolo importante in questa epidemia è giocato dall’anticipazione diagnostica, che, per un tumore a così bassa letalità, quasi sicuramente è anche sovradiagnosi.

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

1. Hassan C, Pooler BD, Kim DH, Rinaldi A, Repici A, Pickhardt PJ. Computed tomographic colonography for colorectal cancer screening: Risk factors for the detection of advanced neoplasia. Cancer. 2013 Jun 10. doi: 10.1002/cncr.28007. [Epub ahead of print]
Digestive Endoscopy Unit, Nuovo Regina Margherita Hospital, Rome, Italy.

Abstract
BACKGROUND: The objective of this study was to determine whether age, sex, a positive family history of colorectal cancer, and body mass index (BMI) are important predictors of advanced neoplasia in the setting of screening computed tomographic colonography (CTC). METHODS: Consecutive patients who were referred for first-time screening CTC from 2004 to 2011 at a single medical center were enrolled. Results at pathology were recorded for all patients who underwent polypectomy. Logistic regression was used to identify significant predictor variables for advanced neoplasia (any adenoma ≥10 mm or with villous component, high-grade dysplasia, or adenocarcinoma). Odds ratios (ORs) were used to express associations between the study variables (age, sex, BMI, and a positive family history of colorectal cancer) and advanced neoplasia. RESULTS: In total, 7620 patients underwent CTC screening. Of these, 276 patients (3.6%; 95% confidence interval [CI], 3.2%-4.1%) ultimately were diagnosed with advanced neoplasia. At multivariate analysis, age (mean OR per 10-year increase, 1.8; 95% CI, 1.6-2.0) and being a man (OR, 1.7; 95% CI, 1.3-2.2) were independent predictors of advanced neoplasia, whereas BMI and a positive family history of colorectal cancer were not. The number needed to screen to detect 1 case of advanced neoplasia varied from 51 among women aged ≤55 years to 10 among men aged >65 years. The number of post-CTC colonoscopies needed to detect 1 case of advanced neoplasia varied from 2 to 4. CONCLUSIONS: Age and sex were identified as important independent predictors of advanced neoplasia risk in individuals undergoing screening CTC, whereas BMI and a positive family history of colorectal cancer were not. These results have implications for appropriate patient selection.

2. Hassan C, Repici A, Zullo A, Kanakadandi V, Sharma P. Colonic polyps: are we ready to resect and discard? Gastrointest Endosc Clin N Am. 2013 Jul;23(3):663-78. doi: 10.1016/j.giec.2013.03.005. Epub 2013 May 14.
Digestive Endoscopy Unit, IRCCS Istituto Clinico Humanitas, Via Manzoni 56, Rozzano, Milan 20089, Italy. Electronic address: cesareh@hotmail.com.

Abstract
Colorectal cancer represents a major cause of mortality in Western countries, and population-based colonoscopy screening is supported by official guidelines. A significant determinant of the cost of colonoscopy screening/surveillance is driven by polypectomy of diminutive (≤5 mm) lesions. When considering the low prevalence of advanced neoplasia within diminutive polyps, the additional cost of pathologic examination is mainly justified by the need to differentiate between precancerous adenomatous versus hyperplastic polyps. The aim of this review is to summarize the data supporting the clinical application of a resect and discard strategy, also addressing the potential pitfalls associated with this approach.

3. Zucchetto A, Ronco G, Giorgi Rossi P, Zappa M, Ferretti S, Franzo A, Falcini F, Visioli CB, Zanetti R, Biavati P, La Rosa F, Baracco S, Federico M, Campari C, De Togni A, Piffer S, Pannozzo F, Fusco M, Michiara M, Castaing M, Seghini P, Tisano F, Serraino D; IMPATTO CERVICE Working Group.. Screening patterns within organized programs and survival of Italian women with invasive cervical cancer. Prev Med. 2013 Jun 1. pii: S0091-7435(13)00181-3. doi: 10.1016/j.ypmed.2013.05.018. [Epub ahead of print]
Epidemiology and Biostatistics Unit, Aviano National Cancer Institute Centro di riferimento oncologico, Via Gallini 2, 33081 Aviano (PN), Italy; Clinical Sciences and Community Health, Milan University, Via Vanzetti 5, 20133 Milano, Italy. Electronic address: zucchetto.epi@cro.it.

Abstract
OBJECTIVES: To evaluate screening patterns within organized cervical screening programs (OCSPs) and survival of women with invasive cervical cancer (ICC). METHODS: A population-based study was conducted in Italian areas covered by cancer registries and OCSPs. The study included all women aged 25-65years diagnosed with ICC between 1995 and 2008, and their screening histories within OCSPs were retrieved. Hazard ratios (HR) of death and 95% confidence intervals (CI) were computed according to screening pattern, using Cox models adjusted for age, ICC stage, and major confounders. RESULTS: Among 3268 women with ICC, 20% were never-invited to OCSP, 36% were never-compliant with OCSP's invitation, 33% were compliant and had a screen-detected ICC within OCSP (i.e., after a positive cytology), and 11% were compliant but had a non-screen-detected ICC. Screen-detected ICCs were more frequently micro-invasive (42%) compared to non-screen-detected ones (14%). Compared to women with screen-detected ICC, the adjusted HRs of death were 1.9 (95% CI 1.5-2.4) for those never-invited, 2.0 (95% CI 1.6-2.5) for never-compliant, and 1.7 (95% CI 1.3-2.4) for compliant women having non-screen-detected ICC. CONCLUSION: Prolonged survival, beyond down-staging, of women with ICC detected within OCSPs in Italy, further calls for improvements of OCSPs' invitational coverage and participation.

4. Sassoli de Bianchi P, Campari C, Mancini S, Giuliani O, Landi P, Paterlini L, Naldoni C, Finarelli AC, Falcini F, Ponz de Leon M, Sassatelli R, Borciani E, Fornari F, Gatti G, Zatelli M, Zurlini C, Rossi F, Corradini R, Olivetti R, Manfredi M, Baldazzi P, Nannini R, Zanarini S, Matarese VG, Palmonari C, Triossi O, Gordini S, Vattiato R, Colamartini A, Palazzi M, Severi M, Briganti L, Giovanardi M, Casale C, Bucchi L. Colonoscopic surveillance of first-degree relatives of colorectal cancer patients in a faecal occult blood screening programme. Cancer Epidemiol. 2013 Aug;37(4):469-73. doi: 10.1016/j.canep.2013.04.004. Epub 2013 May 14.
Department of Health, Emilia-Romagna Region, 40127 Bologna, Italy.

Abstract
Background: In some Italian areas, colonoscopic surveillance of first-degree relatives (FDRs) of colorectal cancer (CRC) patients is provided as a part of local population-based faecal occult blood test (FOBT) screening programmes. The objective of the present study was to assess the feasibility and early results of this surveillance model. Methods: Data from district screening centres were used to evaluate the process of identification and selection of eligible FDRs (residence in the Emilia-Romagna Region, age 40-75 years, no recent colonoscopy) of screen-detected CRC patients and the detected prevalence of disease. The probability for an FDR to undergo colonoscopy and to be diagnosed with CRC and advanced adenoma was estimated using the Kaplan-Meier method. The sex- and age-standardised ratio of detected prevalence to that expected based on results from a colonoscopy screening study of the Italian general population was estimated. Results: Between 2005 and 2011, 9319 FDRs of 2437 screen-detected CRC patients (3.8 per patient) were identified and contacted. Their likelihood of being eligible for, and accepting, colonoscopy was 0.11 (95% confidence interval: 0.11-0.12). Among the 926 subjects undergoing colonoscopy, the prevalence of previous negative screening FOBT was 63%. Eleven CRCs (1.2%) and 100 advanced adenomas (10.8%) were detected. The standardised ratio of detected prevalence to that expected was 0.91 (95% confidence interval: 0.19-2.66) for CRC and 1.48 (1.04-2.05) for advanced adenoma. Conclusions: The procedure of selection of FDRs was extremely ineffective. Due to previous negative screening tests, the prevalence of disease was less than expected. A population-based FOBT screening programme is a highly unsuitable setting for the provision of surveillance to FDRs of CRC patients.

5. Infante M, Berghmans T, Heuvelmans MA, Hillerdal G, Oudkerk M. Slow-growing lung cancer: an emerging entity from screening to clinical management. Eur Respir J. 2013 May 16. [Epub ahead of print]
IRCCS Istituto Clinico Humanitas, Milan, Italy.

Abstract
The current paradigm is that untreated lung cancer is invariably and rapidly fatal, therefore the medical community normally dismisses the idea that a patient could live with such a disease for years without any therapy.Yet, evidence from lung cancer screening research and from recent clinical series suggests that, although rarely recognized in routine practice, slow-growing lung cancers do exist and are more common than previously thought.Current evidence is reviewed and clinical cases are illustrated to show that slow-growing lung cancer is a real clinical entity, and the reasons why management protocols developed in the screening setting may also be useful in clinical practice are discussed. Features suggesting that a lung cancer may be slow-growing are described and appraised, areas of uncertainty are examined, modern management options for early-stage disease are appraised, and the influence that all this knowledge might have on our clinical decision-making is weighed. Further research directed at developing appropriate guidelines for these peculiar but increasingly common patients is warranted.

6. Camilloni L, Ferroni E, Cendales BJ, Pezzarossi A, Furnari G, Borgia P, Guasticchi G, Giorgi Rossi P; Methods to increase participation Working Group. Methods to increase participation in organised screening programs: a systematic review. BMC Public Health. 2013 May 13;13:464. doi: 10.1186/1471-2458-13-464.
Epidemiology Unit, AUSL Reggio Emilia, Reggio Emilia, Italy. paolo.giorgirossi@ausl.re.it.

Abstract
BACKGROUND: The European Community recommends the implementation of population-based screening programmes for cervical, breast, and colorectal cancers. This recommendation is supported by many observational studies showing that organised programmes effectively reduce mortality and control the inappropriate use of screening tests. We conducted a systematic review of studies assessing the efficacy of interventions to increase participation in organised population-based screening programs. METHODS: We included all studies on interventions aimed at increasing screening participation published between 1/1999 and 7/2012. For those published before 1999, we considered the Jepson et al. (2000) review (Health Technol Assess 4:1-133, 2000). RESULTS: Including studies from the Jepson review, we found 69 with quantitative information on interventions in organised screening: 19 for cervical, 26 for breast, 20 colorectal cancers, and 4 for cervical and breast cancer together.Effective interventions were: postal (breast RR = 1,37 95% Confidence Interval (95% CI): 1.25-1.51; cervical RR = 1.71 95% CI: 1.60-1.83; colorectal RR = 1.33 95% CI: 1.17-1.51) and telephone reminders (with heterogeneous methods for implementation); GP's signature on invitation letter (breast RR = 1.13 95% CI: 1.11-1.16; cervical RR = 1.20 95% CI: 1.10-1.30; colorectal RR = 1.15 95% CI: 1.07-1.24); scheduled appointment instead of open appointment (breast RR = 1.26 95% CI: 1.02-1.55; cervical RR = 1.49 95% CI: 1.27-1.75; colorectal RR = 1.79 95% CI: 1.65-1.93). Mailing a kit for self-sampling cervical specimens increased participation in non-responders (RR = 2.37 95% CI: 1.44-3.90). CONCLUSION: Although some interventions did prove to be effective, some specific variables may influence their effectiveness in and applicability to organised population-based screening programs.

7. Ciatto S, Houssami N, Bernardi D, Caumo F, Pellegrini M, Brunelli S, Tuttobene P, Bricolo P, Fantò C, Valentini M, Montemezzi S, Macaskill P. Integration of 3D digital mammography with tomosynthesis for population breast-cancer screening (STORM): a prospective comparison study. Lancet Oncol. 2013 Jun;14(7):583-9. doi: 10.1016/S1470-2045(13)70134-7. Epub 2013 Apr 25.
UO Senologia Clinica e Screening Mammografico, Department of Diagnostics, Azienda Provinciale Servizi Sanitari, Trento, Italy; Centro di Prevenzione Senologica, Marzana, Verona, Italy.

Abstract
BACKGROUND: Digital breast tomosynthesis with 3D images might overcome some of the limitations of conventional 2D mammography for detection of breast cancer. We investigated the effect of integrated 2D and 3D mammography in population breast-cancer screening. METHODS: Screening with Tomosynthesis OR standard Mammography (STORM) was a prospective comparative study. We recruited asymptomatic women aged 48 years or older who attended population-based breast-cancer screening through the Trento and Verona screening services (Italy) from August, 2011, to June, 2012. We did screen-reading in two sequential phases-2D only and integrated 2D and 3D mammography-yielding paired data for each screen. Standard double-reading by breast radiologists determined whether to recall the participant based on positive mammography at either screen read. Outcomes were measured from final assessment or excision histology. Primary outcome measures were the number of detected cancers, the number of detected cancers per 1000 screens, the number and proportion of false positive recalls, and incremental cancer detection attributable to integrated 2D and 3D mammography. We compared paired binary data with McNemar's test. FINDINGS: 7292 women were screened (median age 58 years [IQR 54-63]). We detected 59 breast cancers (including 52 invasive cancers) in 57 women. Both 2D and integrated 2D and 3D screening detected 39 cancers. We detected 20 cancers with integrated 2D and 3D only versus none with 2D screening only (p<0•0001). Cancer detection rates were 5•3 cancers per 1000 screens (95% CI 3•8-7•3) for 2D only, and 8•1 cancers per 1000 screens (6•2-10•4) for integrated 2D and 3D screening. The incremental cancer detection rate attributable to integrated 2D and 3D mammography was 2•7 cancers per 1000 screens (1•7-4•2). 395 screens (5•5%; 95% CI 5•0-6•0) resulted in false positive recalls: 181 at both screen reads, and 141 with 2D only versus 73 with integrated 2D and 3D screening (p<0•0001). We estimated that conditional recall (positive integrated 2D and 3D mammography as a condition to recall) could have reduced false positive recalls by 17•2% (95% CI 13•6-21•3) without missing any of the cancers detected in the study population. INTERPRETATION: Integrated 2D and 3D mammography improves breast-cancer detection and has the potential to reduce false positive recalls. Randomised controlled trials are needed to compare integrated 2D and 3D mammography with 2D mammography for breast cancer screening. FUNDING: National Breast Cancer Foundation, Australia; National Health and Medical Research Council, Australia; Hologic, USA; Technologic, Italy.

8. Terzi A, Bertolaccini L, Viti A, Comello L, Ghirardo D, Priotto R, Grosso M; SOS Study Group. Lung Cancer Detection with Digital Chest Tomosynthesis: Baseline Results from the Observational Study SOS. J Thorac Oncol. 2013 Jun;8(6):685-92. doi: 10.1097/JTO.0b013e318292bdef.
*Thoracic Surgery Unit, Department of Surgery, and †Department of Radiology, S. Croce City Hospital, Cuneo Italy.

Abstract
INTRODUCTION: : Observational studies consistently support strategies for early cancer diagnosis and treatment. Owing to its high prevalence, mortality rate, and easily identifiable at-risk population groups, lung cancer seems ideal for early detection programs. We present the baseline results of the SOS study, a single-arm observational study of digital chest tomosynthesis for lung cancer detection in an at-risk population. METHODS: : Accrual of study participants started in December 2010 and ended in December 2011. Participants considered eligible were smokers or former smokers aged 45 to 75 years, with a smoking history of at least 20 pack-years, without malignancy in the 5 years before the start of the study. A tomosynthesis examination was performed at baseline and another the year after. RESULTS: : Of the 1919 candidates assessed, 1843 (96%) were enrolled into the study: the mean age was 61 years (range, 48-73 years); 1419 (77%) were current smokers. The most prevalent comorbidities were hypertension, chronic obstructive pulmonary disease, and cardiovascular diseases. A total of 1843 tomosynthesis studies were obtained. Pulmonary abnormalities were detected in 268 subjects (14.5%). First-line basal computed tomography (CT) was subsequently carried out in 132 subjects (7.2%), 68 (4.9%) of which were referred for follow-up CT. Positron-emission tomography/CT was performed on 27 individuals (1.46%), and lung cancer was detected in 18 (0.98%) of them. CONCLUSION: : The detection rate of noncalcified lung nodules for tomosynthesis was comparable with rates reported for CT. A small subgroup underwent low-dosage CT and entered a follow-up program. Overall, lung cancer was detected in approximately 1% of cases. Digital chest tomosynthesis holds promise as a first-line lung cancer screening tool.

9. Gnarini VL, Brigante G, Della Valle E, Diazzi C, Madeo B, Carani C, Rochira V, Simoni M. Very high prevalence of ultrasound thyroid scan abnormalities in healthy volunteers in Modena, Italy. J Endocrinol Invest. 2013 Apr 12. [Epub ahead of print]
Unit and Chair of Endocrinology & Metabolism, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia.

Abstract
Background: Italy is characterized by high prevalence of goiter. To date, only limited data about the prevalence of goiter in the Italian adult population are available. Aim. To investigate the prevalence of thyroid ultrasound abnormalities in adults unaware of any thyroid disease and evaluate the rate of differentiated thyroid cancer (DTC) obtained by this intervention. Methods. US thyroid scan was performed in adult volunteers recruited by advertisement in Modena, Italy. 135 women and 66 men (n= 201), unaware of any thyroid disease (mean age of 46 ± 10.7 years) underwent their first thyroid US scan. Results. US thyroid abnormalities were found in 101 subjects (50.3%): 91 nodular goiters (45.2%) and 13 US-thyroiditis (6.5%) associated with positive auto-antibodies in 11 of them. 17 subjects (18%) with nodules underwent US-FNAB with the following cytological class (C) outcome: 14 patients C2 (82 %), 1 patient C3 (6 %), 2 patients had C4 (12%), the latter received histological confirmation. Conclusions. The prevalence of thyroid abnormalities, is very high in subjects unaware of any thyroid disease. DTC was found in 1% of subjects and in 2% of those affected by nodular goiter. Compared to the detection rate of the well-established screening programs for breast (0.45%) and colorectal (0.27%) cancer, the prevalence of DTC seems to be much higher. Thyroid US screening could allow the detection of DTC in asymptomatic subjects and this diagnosis often includes DTC at an advanced stage. Thus, US screening not necessarily results in the over-diagnosis of clinically not relevant thyroid diseases.

10. Venturini E, Losio C, Panizza P, Rodighiero MG, Fedele I, Tacchini S, Schiani E, Ravelli S, Cristel G, Panzeri MM, De Cobelli F, Del Maschio A. Tailored Breast Cancer Screening Program with Microdose Mammography, US, and MR Imaging: Short-term Results of a Pilot Study in 40-49-Year-Old Women. Radiology. 2013 Apr 11. [Epub ahead of print]
Department of Radiology, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy; Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy; Department of Radiology, Fondazione IRCSS Istituto Nazionale Tumori, Milan, Italy.

Abstract
Purpose:To evaluate the feasibility, performance, and cost of a breast cancer screening program aimed at 40-49-year-old women and tailored to their risk profile with supplemental ultrasonography (US) and magnetic resonance (MR) imaging.Materials and Methods:The institutional review board approved this study, and informed written consent was obtained. A total of 3017 40-49-year-old women were invited to participate. The screening program was tailored to lifetime risk (Gail test) and mammographic density (according to Breast Imaging Reporting and Data Systems [BI-RADS] criteria) with supplemental US or MR imaging and bilateral two-view microdose mammography. The indicators suggested by European guidelines, US incremental cancer detection rate (CDR), and estimated costs were evaluated.Results:A total of 1666 women (67.5% participation rate) were recruited. The average lifetime risk of breast cancer was 11.6%, and nine women had a high risk of breast cancer; 917 women (55.0%) had a high density score (BI-RADS density category 3 or 4). The average glandular dose for screening examinations was 1.49 mGy. Screening US was performed in 835 study participants (50.1%), mostly due to high breast density (800 of 1666 women [48.0%]). Screening MR imaging was performed in nine women (0.5%) at high risk for breast cancer. Breast cancer was diagnosed in 14 women (8.4 cases per 1000 women). Twelve diagnoses were made with microdose mammography, and two were made with supplemental US in dense breasts (2.4 cases per 1000 women). All patients were submitted for surgery, and 10 underwent breast-conserving surgery. The sentinel lymph node was evaluated in 11 patients, resulting in negative findings in six. Pathologic analysis resulted in the diagnosis of four ductal carcinomas in situ and 10 invasive carcinomas (five at stage I).Conclusion:A tailored breast cancer screening program in 40-49-year-old women yielded a greater-than-expected number of cancers, most of which were low-stage disease.© RSNA, 2013.

11. Gnagnarella P, Maisonneuve P, Bellomi M, Rampinelli C, Bertolotti R, Spaggiari L, Palli D, Veronesi G. Nutrient intake and nutrient patterns and risk of lung cancer among heavy smokers: results from the COSMOS screening study with annual low-dose CT. Eur J Epidemiol. 2013 Apr 11. [Epub ahead of print]
Division of Epidemiology and Biostatistics, European Institute of Oncology, Via Ramusio 1, Milan, 20141, Italy, patrizia.gnagnarella@ieo.it.

Abstract
The role of nutrients in lung cancer aetiology remains controversial and has never been evaluated in the context of screening. Our aim was to investigate the role of single nutrients and nutrient patterns in the aetiology of lung cancer in heavy smokers. Asymptomatic heavy smokers (≥20 pack-years) were invited to undergo annual low-dose computed tomography. We assessed diet using a self-administered food frequency questionnaire and collected information on multivitamin supplement use. We performed principal component analysis identifying four nutrient patterns and used Cox proportional Hazards regression to assess the association between nutrients and nutrients patterns and lung cancer risk. During a mean follow-up of 5.7 years, 178 of 4,336 participants were diagnosed with lung cancer by screening. We found a significant risk reduction of lung cancer with increasing vegetable fat consumption (HR for highest vs. lowest quartile = 0.50, 95 % CI = 0.31-0.80; P-trend = 0.02). Participants classified in the high "vitamins and fiber" pattern score had a significant risk reduction of lung cancer (HR = 0.57; 95 % CI = 0.36-0.90, P-trend = 0.01). Among heavy smokers enrolled in a screening trial, high vegetable fat intake and adherence to the "vitamin and fiber" nutrient pattern were associated with reduced lung cancer incidence.

12. Pastorino U. Current status of lung cancer screening. Thorac Surg Clin. 2013 May;23(2):129-40. doi: 10.1016/j.thorsurg.2013.01.018.
Division of Thoracic Surgery, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy. Ugo.Pastorino@istitutotumori.mi.it

Abstract
Low-dose CT (LDCT) is effective in the early detection of lung cancer, providing higher resectability and long-term survival rates. The National Lung Screening Trial shows a statistically significant mortality reduction in LDCT compared with chest radiography. The efficacy and safety of annual LDCT screening in heavy smokers must be explored, and the magnitude of benefit compared with the cost of large-scale screening. Trials in Europe have different study designs and an observational arm. Strategies to reduce lung cancer mortality should combine early detection with primary prevention and innovative biologic approaches.

13. Khadjavi A, Notarpietro A, Mannu F, Pantaleo A, Ferru E, Destefanis P, Fontana D, Turrini F. A high-throughput assay for the detection of Tyr-phosphorylated proteins in urine of bladder cancer patients. Biochim Biophys Acta. 2013 Jun;1830(6):3664-9. doi: 10.1016/j.bbagen.2013.03.016. Epub 2013 Mar 23.
Department of Oncology, University of Turin Medical School, Turin, Italy. amina.khadjavi@unito.it

Abstract
BACKGROUND: Bladder cancer has the peculiarity of shedding neoplastic cells and their components in urine representing a valuable opportunity to detect diagnostic markers. Using a semi-quantitative method we previously demonstrated that the levels of Tyr-phosphorylated proteins (TPPs) are highly increased in bladder cancer tissues and that soluble TPPs can also be detected in patient's urine samples. Although the preliminary evaluation showed very promising specificity and sensitivity, insufficient accuracy and very low throughput of the method halted the diagnostic evaluation of the new marker. To overcome this problem we developed a quantitative methodology with high sensitivity and accuracy to measure TPPs in urine. METHODS: The Immobilized Metal Affinity Chromatography (IMAC) was miniaturized in a 96 well format. Luminescence, visible and infrared fluorescence antibody-based detection methods were comparatively evaluated. RESULTS: Due to their low abundance we evidenced that both phosphoprotein enrichment step and very sensitive detection methods are required to detect TPPs in urine samples. To pursue high throughput, reproducibility and cost containment, which are required for bladder cancer screening programs, we coupled the pre-analytical IMAC procedure with high sensitive detection phases (infrared fluorescence or chemiluminescence) in an automated platform. CONCLUSIONS: A high throughput method for measuring with high sensitivity TPP levels in urine samples is now available for large clinical trial for the establishment of the diagnostic and predictive power of TPPs as bladder cancer marker. GENERAL SIGNIFICANCE: The new assay represents the first quantitative and high throughput method for the measurement of TPPs in urine.

14. Foca F, Mancini S, Bucchi L, Puliti D, Zappa M, Naldoni C, Falcini F, Gambino ML, Piffer S, Sanoja Gonzalez ME, Stracci F, Zorzi M, Paci E; IMPACT Working Group. Decreasing incidence of late-stage breast cancer after the introduction of organized mammography screening in Italy. Cancer. 2013 Jun 1;119(11):2022-8. doi: 10.1002/cncr.28014. Epub 2013 Mar 15.
Romagna Cancer Registry, Romagna Cancer Institute, Meldola, Forli, Italy.

Abstract
BACKGROUND: After the introduction of a mammography screening program, the incidence of late-stage breast cancer is expected to decrease. The objective of the current study was to evaluate variations in the total incidence of breast cancer and in the incidence of breast cancers with a pathologic tumor (pT) classification of pT2 through pT4 after the introduction of mammography screening in 6 Italian administrative regions. METHODS: The study area included 700 municipalities, with a total population of 692,824 women ages 55 to 74 years, that were targeted by organized mammography screening between 1991 and 2005. The year screening started at the municipal level (year 1) was identified. The years of screening were numbered from 1 to 8. The ratio of the observed 2-year, age-standardized (Europe) incidence rate to the expected rate (the incidence rate ratio [IRR]) was calculated. Expected rates were estimated assuming that the incidence of breast cancer was stable and was equivalent to that in the last 3 years before year 1. RESULTS: The study was based on a total of 14,447 incident breast cancers, including 4036 pT2 through pT4 breast cancers. The total IRR was 1.35 (95% confidence interval, 1.03-1.41) in years 1 and 2, 1.16 (95% confidence interval, 1.10-1.21) in years 3 and 4, 1.14 (95% confidence interval, 1.08-1.20) in years 5 and 6, and 1.14 (95% confidence interval, 1.08-1.21) in years 7 and 8. The IRR for pT2 through pT4 breast cancers was 0.97 (95% confidence interval, 0.90-1.04) in years 1 and 2, 0.81 (95% confidence interval, 0.75-0.88) in years 3 and 4, 0.79 (95% confidence interval, 0.73-0.87) in years 5 and 6, and 0.71 (95% confidence interval, 0.64-0.79) in years 7 and 8. CONCLUSIONS: A significant and stable decrease in the incidence of late-stage breast cancer was observed from the third year of screening onward, when the IRR varied between 0.81 and 0.71. Cancer 2013;119:2022-2028. © 2013 American Cancer Society.

15. D'Urso V, Doneddu V, Marchesi I, Collodoro A, Pirina P, Giordano A, Bagella L. Sputum analysis: non-invasive early lung cancer detection. J Cell Physiol. 2013 May;228(5):945-51. doi: 10.1002/jcp.24263.
INT-CROM, Pascale Foundation National Cancer Institute, Cancer Research Center, Mercogliano, Italy.

Abstract
Lung cancer is the leading cause of cancer-related deaths over the world, characterized by a very high mortality rate. Molecular technique development tries to focus on early detection of cancers by studying molecular alterations that characterize cancer cells. Worldwide lung cancer research has focused on an ever-increasing number of molecular elements of carcinogenesis at genetic, epigenetic and protein levels. The non-invasiveness is the characteristic that all clinical trials on cancer detection should have. Abnormal chest imaging and/or non-specific symptoms are initial signals of lung cancer that appear in an advanced stage of disease. This fact represents the cause of the low 5-year survival rate: over 90% of patients dying within 5 years of diagnosis. Since smokers have higher quantity of sputum containing exfoliated cells from the bronchial tree, and the sputum represents the most easily accessible biological fluid and its collection is non-invasive, analysis of this sample represents a good area of research in early lung cancer diagnosis. Continued cigarette smoking is the cause of chronic obstructive pulmonary disease (COPD), with an estimated attributable risk factor exceeding 80% in smoking affected individuals. Lung cancer is found in 40-70% of patients with COPD, particularly in severe disease, and it is a common cause of death in these patients. A large prospective trial of almost half a million non-smokers showed as lung cancer is also common in patients with COPD who have never smoked. This review describes issues related to early lung cancer screening using non-invasive methods.

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