rubrica

Screening

  • Paolo Giorgi Rossi1

  1. AUSL Reggio Emilia
Paolo Giorgi Rossi -

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Ricerca bibliografica periodo dal 1giugno 2012 al 15 agosto 2012

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Stringa: ("mass screening"[MeSH Terms] OR cancer[Title/Abstract] AND screening[Title/Abstract] AND ("italy"[MeSH Terms] OR "italy"[All Fields]) AND ("2012/06/01"[PDAT] : "2012/08/15"[PDAT])

Breve commento a cura di P. Giorgi Rossi
In questi due mesi e mezzo sono usciti due lavori (Della Corte, Ruggeri) che riguardano uno screening oncologico che fino ad ora non avevamo ancora incontrato nella letteratura italiana sull’argomento ed è quello del carcinoma epatocellulare nei soggeti ad alto rischio (cirrotici, epatite B cronica, ma anche soggetti con malattie metaboliche correlate a insulino-resistenza). Quattro lavori riguardano lo screening del colon retto, due del polmone, due della mammella e due della cervice, tra cui l’ennesimo lavoro che viene dal trial NTCC (Giorgi Rossi). Non muore mai la polemica sull’efficacia dello screening mammografico e l’esortazione di Segnan e colleghi ad andare oltre è quanto mai appropriata: oramai il tumore della mammella è in larga parte diagnosticato in donne asintomatiche, questo è il contesto in cui si deve operare cercando di garantire qualità della diagnosi e delle cure a tutte le donne. Per il polmone ancora una volta gli outcome secondari producono risultati a ritmi ben più serrati degli outcome principali: interessante l’analisi dei reperti occasionali nella TAC spirale (Priola). Per la cervice uterina arriva un altro studio Italiano di validazione di un test per l’HPV. In un campo dove la concorrenza è iniziata da poco, fa piacere che si rendano disponibili più test commerciali e competano più produttori. Peccato però che lo studio non abbia seguito le linee guida per la validazione dei test HPV per lo screening proposte nel 2009 da Majier e colleghi (Int J Cancer 2009; 124:516-520).

1. Barzon L, Militello V, Pagni S, Palù G. Comparison of INNO-LiPA Genotyping Extra and Hybrid Capture 2 assays for detection of carcinogenic human papillomavirus genotypes. J Clin Virol. 2012 Aug 6. [Epub ahead of print]
Department of Molecular Medicine, University of Padova, Padova, Italy; Microbiology and Virology Unit, Padova University Hospital, Padova, Italy.

Abstract
BACKGROUND: Accurate HPV detection and genotyping tests are useful for management of women with HPV infection and for monitoring HPV vaccine efficacy. OBJECTIVES: To evaluate the performance of the INNO-LiPA HPV Genotyping Extra assay (SPF10-LiPA) for the detection of carcinogenic HPV types in women referred for opportunistic cervical cancer screening by comparison with the Hybrid Capture 2 (HC2) assay. STUDY DESIGN: Cross-sectional analysis from baseline data of HC2 and SPF10-LiPA testing in cervical specimens collected from 1580 consecutive women and correlation with cervical cytology and histology data, when available. RESULTS: The two assays showed a good agreement for detection of carcinogenic HPV types and reported the same prevalence of carcinogenic HPV infections in different age groups. Stratification of study subjects by cervical cytology interpretation and histology results demonstrated that the two tests gave very similar results in the different cytology interpretation groups and in CIN2 and CIN3 samples, while in <CIN2 samples the SPF10-LiPA assay provided a significantly lower number of carcinogenic HPV-positive results than the HC2 test. A comparative analysis of the two assay for individual HPV types showed that HC2 identified as positive between 73% and 100% of specimens with carcinogenic HPV types detected by SPF10-LiPA and, in particular, approximately 90% and 80% of HPV16- and HPV18-positive samples, respectively. CONCLUSIONS: A good agreement was observed between HC2 and SPF10-LiPA for carcinogenic HPV type detection, that supports further evaluation of the clinical performance of the new version of SPF10-LiPA in cervical cancer screening protocols.

2. Priola AM, Priola SM, Giaj-Levra M, Basso E, Veltri A, Fava C, Cardinale L. Clinical Implications and Added Costs of Incidental Findings in an Early Detection Study of Lung Cancer by Using Low-Dose Spiral Computed Tomography. Clin Lung Cancer. 2012 Aug 3. [Epub ahead of print]
Department of Diagnostic Imaging, San Luigi Gonzaga University Hospital, Orbassano (Torino), Italy.

Abstract
INTRODUCTION: To prospectively evaluate the frequency and spectrum of incidental findings (IF) in a 5-year lung cancer screening program with low-dose spiral computed tomography (CT) and to estimate the additional costs of their imaging workup incurred from subsequent radiologic follow-up evaluation. MATERIALS AND METHODS: A total of 519 asymptomatic volunteers were enrolled. All IFs were reported and were considered clinically relevant if they required further evaluations or with clinical implications if they required more than one additional diagnostic test for characterization or medical and/or surgical intervention. RESULTS: IFs were commonly found (59.2%, 307/519 participants at baseline and 5.3% per year at 5-year follow-up [123 participants of 2341 LDsCT exams performed during follow-up], with an overall rate of 26.3%). IFs were categorized as previously unknown clinically relevant in 52 (10.0%) individuals at baseline. Of these, 36 (6.9%) individuals had IFs with clinical implications (10 clinically relevant, of which 6 had clinical implications, detected during the subsequent 5-year follow-up). The most common recommendations were for additional imaging of the thyroid and kidneys. Additional imaging was mainly performed by ultrasound (43/68 [63.2%]). Subsequent surgical intervention resulted from these findings in 7 (1.5%) subjects. Six malignancies were diagnosed (rate, 0.2% per year). Costs of subsequent radiologic follow-up studies were calculated as €4644.56 [U.S. $6575.04] at baseline and €1052.30 [U.S. $1489.69] at 5-year follow-up (average added costs per participant €8.95 [U.S. $12.67] and €2.25 [U.S. $3.19], respectively). CONCLUSIONS: Low-dose spiral CT commonly detects IFs. Some of these require further investigations to assess their clinical relevance. Although such IFs add little clinical benefit to the screening intervention, moderate incremental costs are incurred based on additional radiologic procedures generated during short-term follow-up, given the potential for positive effects on patient care.

3. Rubeca T, Peruzzi B, Confortini M, Rapi S. Overall evaluation of an immunological latex agglutination system for fecal occult blood testing in the colorectal cancer screening program of Florence. Int J Biol Markers. 2012 Jul 31:0. doi: 10.5301/JBM.2012.9343. [Epub ahead of print]
Cancer Prevention and Research Institute (ISPO), Florence - Italy.

Abstract
Several immunological fecal occult blood tests (FOBT) are currently available for colorectal cancer (CRC) screening. We compared the HM Jack (Jack) (Kiowa, Japan), with the OC-Hemodia (OC) (Eiken, Japan) in use in the Florence screening program. Aims of the study were: (i) to investigate the diagnostic performance and the best cutoff value for Jack; (ii) to evaluate the handiness of sampling tubes; (iii) to compare costs. A total of 5,044 subjects were screened with both tests. Sampling tube investigation was performed running each sample on both instruments. A number of 352 subjects positive for at least one test (175 OC, 310 Jack) were selected for further investigations, while 46 subjects refused further assessments. Analysis of costs related to the assessment phase was performed on the basis of Tuscany region's fares. Amongst the 306 subjects investigated, 9 CRC and 67 advanced adenomas (AdA) were detected. Detection rates (DR) were 1.4‰ for CRC and 9.6‰ for AdA. After Jack cutoff optimization, DR for CRC+AdA resulted in 11.1‰ for OC and 13.3‰ for Jack (p=0.041). Sensitivity of the methods was 73.7 for OC and 88.2 for Jack; specificity was 97.6 for OC and 96.0 for Jack, resulting in an increase of the required assessments from 3.5% to 5.1%. No differences were observed between sampling methods. Despite the lower specificity of Jack, its greater sensitivity makes the method attractive for screening programs. An increase of the costs of 30% for every subject investigated for pathological lesion (CRC+AdA) may be thus foreseen.

4. Della Corte C, Colombo M. Surveillance for hepatocellular carcinoma. Semin Oncol. 2012 Aug;39(4):384-98.
Department of Medicine, First Division of Gastroenterology, Centro AM e A Migliavacca for the Study of Liver Disease, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and Università degli Studi di Milano, Milan, Italy.

Abstract
The only hope for a cure from hepatocellular carcinoma (HCC) rests on early diagnosis as it can be attained through semiannual surveillance with abdominal ultrasound (US) of patients at risk. While the strategy of semiannual screening rests on the growth rate of the tumor that in cirrhotic patients takes 6 months to double its volume, on average, the noninvasive radiological diagnosis of HCC is possible in cirrhotic patients with a de novo HCC and patients with chronic hepatitis B. More recently, metabolic diseases related to insulin resistance, including diabetes and obesity, have been recognized to be causally related to HCC as well, in most patients bridging HCC to the histopathological diagnosis of non-alcoholic steatohepatitis (NASH). While the endpoint of an early diagnosis is achieved quite easily in most patients with >1 cm HCC by computed tomography (CT) or magnetic resonance imaging (MRI) demonstrating the specific pattern of an intense contrast uptake during the arterial phase (wash-in) and contrast wash-out during the venous/delayed phase, nodules <1 cm in size are more difficult to diagnose, almost invariably requiring an enhanced follow up with three monthly examinations with US until they grow in size or change their echo pattern. Owing to the lack of robust controlled evidence demonstrating a clinical benefit of surveillance, the real support for screening for liver cancer comes from the striking differences in response to therapy between screened populations in whom HCC is diagnosed and treated at early stages and patients with more advanced, incidentally detected tumors. This notwithstanding, numerous barriers work against screening effectiveness, including limited or outdated knowledge, lack of financial incentives, and limited access to appropriate testing and treatment. Though strengthening prediction in individual patients is expected to improve the cost-effectiveness ratio of screening, the benefits of approaches like pretreatment patient stratification by clinical, histologic, and genetic scores remain uncertain, while the worthiness of excluding patients with severe comorbidities and aged individuals is still debated.

5. Ruggeri M. Hepatocellular carcinoma: cost-effectiveness of screening. A systematic review. Risk Manag Healthc Policy. 2012;5:49-54. Epub 2012 Jun 19.
Facoltà di Economia, Università Cattolica del Sacro Cuore - sede di Roma, Rome, Italy.

Abstract
Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide. HCC is a potential target for cancer surveillance (or screening) as it occurs in well-defined, at-risk populations. Curative therapy is possible only for small tumors and screening strategy has been recommended by the US, Italian, and other international liver societies and is practiced widely, but its benefits are not clearly established. The objective of this study was to review the available evidence with respect to the cost-effectiveness of key technologies in the prevention HCC. The literature search was conducted with the support of PubMed. Firstly we selected articles by reading the abstracts. Secondly, we read the articles and the revision was further restricted, with the following as inclusion criteria: (1) full economic evaluation of HCC screening programs; (2) comparison between HCC techniques; (3) outcome measures expressed in terms of quality adjusted life years (QALY); (4) full text availability. The initial review of the literature yielded 346 articles. Of those, 288 were excluded at the first stage. Of those excluded, 108 did not meet the target, 106 did not present the cost analysis, 33 did not analyze the treatment of the disease, and in 41 the abstract was not available. Of the 58 included in the first step, seven examined the cost-effectiveness of different HCC screening techniques, seven investigated the cost-effectiveness of HCC screening versus no screening, and one looked at the cost-effectiveness of timing for HCC surveillance and monitoring, while 43 were about HBV vaccination and screening. We included only the seven articles examining the cost-effectiveness of different HCC screening techniques. In general, incidence is the key parameter which determines the cost-effectiveness of HCC screening. Discrepancies in the results exist when determining the type of technology to be used. Ultrasound (US) alone or in association with alpha fetoprotein (AFP) technology is likely to be the most cost effective and the use of computed tomography (CT) gives controversial results.

6. Segnan N, Rosso S, Ponti A. Is the breast cancer mortality decrease in sweden due to screening or treatment? Not the right question. J Natl Cancer Inst. 2012 Jul 18;104(14):1040-1. Epub 2012 Jul 17.
MSc Epi, CPO Piemonte, Unit of Cancer Epidemiology, ASO S Giovanni Battista University Hospital, Via S Francesco da Paola 31, Turin 10123, Italy. nereo.segnan@cpo.it.

Abstract
Nessun abstract disponibile

7. Zompatori M, Mascalchi M, Ciccarese F, Sverzellati N, Pastorino U. Screening for lung cancer using low-dose spiral CT: 10 years later, state of the art. Radiol Med. 2012 Jun 28. [Epub ahead of print]
Sezione di Radiologia, Dipartimento di Scienze Radiologiche e Istocitopatologiche, Università di Bologna, Bologna, Italy, maurizio.zompatori@unibo.it.

Abstract
Ten years after the first papers on this subject, this editorial represents a brief review on lung cancer screening with low-dose spiral CT. The aim is to present the main theoretical and practical problems related to lung cancer screening, the historical background and results of observational studies and the main ongoing randomised controlled trials. In particular, the National Lung Screening Trial (NLST), which was interrupted early, is discussed. The opinion of the authors is that too many questions are still awaiting an answer.

8. Parente F, Marino B, Ilardo A, Fracasso P, Zullo A, Hassan C, Moretti R, Cremaschini M, Ardizzoia A, Saracino I, Perna F, Vaira D. A combination of faecal tests for the detection of colon cancer: a new strategy for an appropriate selection of referrals to colonoscopy? A prospective multicentre Italian study. Eur J Gastroenterol Hepatol. 2012 Jun 24. [Epub ahead of print]
Gastrointestinal Unit, Department of Oncology, A. Manzoni Hospital, Colorectal Cancer Screening Unit Community Health Care Centre, Lecco Statistical Unit, Local Health Care Centre, Bergamo Department of Internal Medicine & Gastroenterology, S. Orsola Hospital, Bologna Gastroenterology Service, ASL Roma Division of Gastroenterology, Regina Margherita Hospital, Rome, Italy.

Abstract
INTRODUCTION: Colonoscopy workload for endoscopy services in Western countries is increasing markedly because of the implementation of faecal occult blood-based mass screening programmes against colorectal cancer (CRC). We therefore explored the possibility of using a combination of faecal tests to prioritize the access to colonoscopy with criteria other than symptoms and/or time of referral. AIMS AND METHODS: We tested a combination of faecal tests [immunochemical faecal occult blood test (i-FOBT), M2-PK, calprotectin] as markers for advanced neoplasia in a selected series of patients requiring colonoscopy for the suspicion of CRC. All the tests were performed in a 1-day stool sample of patients aged 50-80 years, without any dietary restriction, before colonoscopy. RESULTS: A total of 280 patients' stool single samples were analysed. Forty-seven patients had CRC and 85 patients had one or more advanced adenoma(s) at colonoscopy/histology. CRCs were associated with a highly significant increase (P<0.001) in faecal tumour M2-PK (mean 24.2 kU/l), which correlated with Dukes' staging. For CRC detection, i-FOBT was the test with the highest specificity and positive predictive value (0.89 and 0.53), whereas M2-PK had the highest sensitivity and negative predictive value (0.87 and 0.96). Calprotectin showed performance similar to M2-PK in terms of sensitivity and negative predictive value (0.93), but had lower specificity (0.39). The best combination of tests to predict the risk of CRC in this series was i-FOBT+M2-PK, as in patients showing positivity to both markers, the risk of cancer was as high as 79%. CONCLUSION: The combination of i-FOBT and M2-PK is a sensitive tool in clinical practice for the appropriate management of waiting lists for colonoscopy, as it allows the classification of patients into different degrees of priority for investigation, according to their foreseeable risk of CRC.

9. Stockbrugger R. Isolated colorectal cancer screening or integrated cancer prevention? A provocative suggestion! Dig Dis. 2012;30(3):316-9. Epub 2012 Jun 20.
Department of Internal Medicine, University Hospital Ferrara, Italy. rstockbrugger635@gmail.com

Abstract
Colorectal cancer (CRC) screening is still not fully established in the European Union. Recently, the United European Gastroenterology Federation (UEGF) supported CRC screening with the publication of quality guidelines and a written declaration in the European Parliament in favor of European-wide monitored CRC screening and primary prevention of CRC, the latter particularly in young citizens. In this article, the need for population-based CRC screening is once again stressed. In addition, the value of opportunistic CRC screening is pointed out, either as a regional or nation-wide alternative (such as in the USA and Germany) or as a 'forerunner' activity in view of subsequent population-based CRC screening. With regard to other parallel organ-related screening activities in Europe (breast, uterus) and the increasing need for primary prevention of malignant and benign diseases, the question is raised as to whether preventive activities should not be recognized as an integrated and logical part of a 'healthcare chain' offered to all European citizens.

10. Hassan C, Rex DK, Zullo A, Cooper GS. Loss of efficacy and cost-effectiveness when screening colonoscopy is performed by nongastroenterologists. Cancer. 2012 Jun 15. doi: 10.1002/cncr.27664
Division of Gastroenterology, Nuovo Regina Margherita Hospital, Rome, Italy. cesareh@hotmail.com.

Abstract
BACKGROUND: Specialty of the endoscopist has been related to the postcolonoscopy interval risk of colorectal cancer (CRC). However, the impact of such a difference on the long-term CRC prevention rate by screening colonoscopy is largely unknown. METHODS: A Markov model was constructed to simulate the efficacy and cost of colonoscopy screening according to the specialty of the endoscopist in 100,000 individuals aged 50 years until death. The postcolonoscopy interval CRC risk (0.02%) and the relative risk (1.4) of interval CRC between gastroenterologist (GI) endoscopists and non-GI endoscopists were extracted from the literature. Both efficacy and costs were projected over a steady-state US population. Eventual increase in endoscopic capacity when assuming all procedures to be performed by GI endoscopists was simulated. RESULTS: According to the simulation model, screening colonoscopy performed by non-GI endoscopists resulted in a 11% relative reduction in the long-term CRC incidence prevention rate compared with the same procedure performed by GI endoscopists. When projected on the US population, the reduced non-GI efficacy resulted in an additional 3043 CRC cases and the loss of $200 million per year. When increasing the relative risk from 1.4 to 2.0, the difference in the prevention rate between GI endoscopists and non-GI endoscopists increased to 19%. It increased further to 38% when also assuming a 3-fold increase in the risk of interval CRC. An additional 165 screening colonoscopies per endoscopist per year would be required to shift all non-GI procedures to GI endoscopists. CONCLUSIONS: When screening colonoscopy is performed by non-GI endoscopists, a substantial reduction in the long-term CRC prevention rate may be expected. Such difference appeared to be greater when a suboptimal efficacy of colonoscopy in preventing CRC was assumed. A 10-year saving of $2 billion may be expected when shifting all screening colonoscopies from non-GI endoscopists to GI endoscopists. Cancer 2012. © 2012 American Cancer Society.

11. Giorgi Rossi P, Carozzi F, Collina G, Confortini M, Dalla Palma P, De Lillo M, Del Mistro A, Ghiringhello B, Gillio-Tos A, Maioli P, Pellegrini A, Schiboni ML, Segnan N, Zaffina LM, Zorzi M, Ronco G; NTCC Working Group. HPV testing is an efficient management choice for women with inadequate liquid-based cytology in cervical cancer screening. Am J Clin Pathol. 2012 Jul;138(1):65-71.
AUSL Reggio Emilia, Epidemiology Unit, via Amendola 2, Reggio Emilia, 42122 Italy. paolo.giorgirossi@ausl.re.it

Abstract
This study compares colposcopy referrals of 2 management strategies: oncogenic human papillomavirus (HPV)-DNA testing (Hybrid Capture 2 assay, Qiagen, Germantown, MD) and repeat cytology. In the New Technology in Cervical Cancer Trial, 22,708 subjects were randomly assigned to undergo both HPV and liquid-based cytologic testing. Women aged 35 to 60 years old with unsatisfactory cytologic findings were directly referred for colposcopy if the HPV test result was positive, and were referred for repeat cytologic examination if the HPV test result was negative; women aged 25 to 35 years old were referred for repeat cytologic examination independent of HPV test results. A positive or a second unsatisfactory cytologic examination referred women for colposcopy. Five hundred sixty women had unsatisfactory cytologic findings. Colposcopy referral was not significant and slightly higher with HPV testing than repeat cytologic test (9.8% vs 6.8%, P = .11). When cytologic testing was repeated 36.8% were unavailable for follow-up and most of the colposcopies were performed in HPV-negative women. For unsatisfactory cytologic findings, HPV triage is a more logical and efficient management strategy than a repeat cytologic test.

12. Terenziani M, Casalini P, Scaperrotta G, Gandola L, Trecate G, Catania S, Cefalo G, Conti A, Massimino M, Meazza C, Podda M, Spreafico F, Suman L, Gennaro M. Occurrence of Breast Cancer After Chest Wall Irradiation for Pediatric Cancer, as Detected by a Multimodal Screening Program. Int J Radiat Oncol Biol Phys. 2012 Jun 5. [Epub ahead of print]
Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy.

Abstract
PURPOSE: To assess the occurrence of breast cancer (BC) after exposure to ionizing radiation for pediatric cancer, by means of a multimodal screening program. PATIENTS AND METHODS: We identified 86 patients who had received chest wall radiation therapy for pediatric cancer. Clinical breast examination (CBE), ultrasound (US), and mammography (MX) were performed yearly. Magnetic resonance imaging (MRI) was added as of October 2007. We calculated the risk of developing BC by radiation therapy dose, patient age, and menarche before or after primary treatment. RESULTS: Eleven women developed a BC from July 2002-February 2010. The sensitivity of the screening methods was 36% for CBE, 73% for MX, 55% for US, and 100% for MRI; the specificity was 91%, 99%, 95%, and 80% for CBE, MX, US, and MRI, respectively. The annual BC detection rate was 2.9%. The median age at BC diagnosis was 33 years. Although age had no influence, menarche before as opposed to after radiation therapy correlated significantly with BC (P=.027): the annual BC detection rate in the former subgroup was 5.3%. CONCLUSIONS: Mammography proved more sensitive and specific in our cohort of young women than CBE or US. Magnetic resonance imaging proved 100% sensitive (but this preliminary finding needs to be confirmed). Our cohort of patients carries a 10-fold BC risk at an age more than 20 years younger than in the general population.

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