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A letter to the editor is presented commenting on the threat of anthrax, botulism and tularemia in Italy.

Background: The number and projections of cancer survivors are necessary to meet the healthcare needs of patients, while data on cure prevalence, that is, the percentage of patients who will not die of cancer by time since diagnosis, are lacking., Materials and Methods: Data from Italian cancer registries (duration of registration ranged from 9 to 40 years, with a median of 22 years) covering 47% of the population were used to calculate the limited-duration prevalence, the complete prevalence in 2018, projections to 2030, and cure prevalence, by cancer type, sex, age, and time since diagnosis., Results: A total of 3 347 809 people were alive in Italy in 2018 after a cancer diagnosis, corresponding to 5.6% of the resident population. They will increase by 1.5% per year to 4 012 376 in 2030, corresponding to 6.9% of the resident population, 7.6% of women and ∼22% after age 75 years. In 2030, more than one-half of all prevalent cases (2 million) will have been diagnosed by ≥10 years. Those with breast (1.05 million), prostate (0.56 million), or colorectal cancers (0.47 million) will be 52% of all prevalent patients. Cure prevalence was 86% for all patients alive in 2018 (87% for patients with breast cancer and 99% for patients with thyroid or testicular cancer), increasing with time since diagnosis to 93% for patients alive after 5 years and 96% after 10 years. Among patients who survived at least 5 years, the excess risk of death (1 - cure prevalence) was <5% for patients with most cancer types except for those with cancers of the breast (8.3%), lung (11.1%), kidney (13.2%), and bladder (15.5%)., Conclusions: Study findings encourage the implementation of evidence-based policies aimed at improving long-term clinical follow-up and rehabilitation of people living after cancer diagnosis throughout the course of the disease. Updated estimates of complete prevalence are important to enhance data-driven cancer control planning., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A recent research project using data from a total of 40 cancer registries has provided new epidemiologic insights into the results of efforts for melanoma control in Italy between the 1990s and the last decade. In this article, the authors present a summary and a commentary of their findings. Incidence increased significantly throughout the study period in both sexes. However, the rates showed a stabilization or a decrease in men and women aged below 35 years. The risk of disease increased for successive cohorts born until 1973 (women) and 1975 (men) while subsequently tending to decline. The trend towards decreasing tumor thickness and increasing survival has continued, but a novel favorable prognostic factor has emerged since 2013 for patients - particularly for males - with thick melanoma, most likely represented by molecular targeted therapies and immune checkpoint inhibitors. Due to this, the survival gap between males and females has been filled out. In the meanwhile, and despite the incidence increase, dermatologists have not lowered their threshold to perform skin biopsy. Skin biopsy rate has increased because of the increasingly greater volume of dermatologic office visits, but the proportion of skin biopsies out of dermatologic office visits has remained constant. In summary, an important breakthrough in melanoma control in Italy has taken place. Effective interventions have been implemented across the full scope of care, which involve many large local populations - virtually the whole national population. The strategies adopted during the last three decades represent a valuable basis for further steps ahead in melanoma control in Italy.

A study was conducted to assess the fraction of female breast cancer (BC) deaths attributable to alcohol consumption in Italy. National mortality data for the period 2015-2019 were used along with national estimates of women from the general population exposed to moderate (11-20 gr/day) or heavy (>20 gr/day) alcohol consumption. From 2015 to 2019, 2918 (4.6%) out of 63,428 BC| deaths were attributable to alcohol consumption, including 1269 deaths (2.0%) caused by moderate consumption. Study findings could help stakeholders to prioritize programs aimed at reducing alcohol consumption, and to improve ways to effectively communicate alcohol-related health risks, including moderate consumption., Competing Interests: Declaration of competing interest All Authors declare that they have no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To describe the practice of prostate-specific antigen (PSA) testing over more than 20 years in Friuli Venezia Giulia (FVG), North-Eastern Italy., Methods: A population-based, ecological study was conducted using information derived from regional administrative health-related databases. Data on PSA and prostate biopsies performed on resident men aged ⩾45 years from 1998 to 2019 were retrieved. PSA and biopsy rates were calculated as the number of men who had at least one such procedure in each calendar year over the mean resident male population of the same year. Temporal trends were analyzed using joinpoint regression (annual percentage change -APC)., Results: A total of 2,502,670 PSA were made between 1998 to 2019 in men aged ⩾45 years. The number of PSA steadily increased from 51,055 in 1998-1999 to 134,504 in 2010-2011, then dropped to 122,080 in 2018-2019. Significant changes in the slopes of PSA rates emerged in 2002 and 2009: the largest increase occurred during 1998-2002 (APC 18.4), followed by a smaller increase in 2002-2009 (APC 3.4) and a subsequent reduction (APC -2.5). Similar patterns emerged for all ages, but the decrease since 2009 was smaller for men aged ⩾65 years. An upward trend emerged in biopsy rate from 1998 to 2001 (APC 13.0), followed by a smaller increase until 2007 (APC 5.7) and a subsequent decrease. Biopsies as percentage of PSA decreased from 3.2% to 2.2%, particularly in those aged ⩾75 years., Conclusions: Although overall declining PSA rates have been observed in FVG since 2009, rates remained higher in the ⩾65-year-old group than in the 45-64-year-old group.

The impact of specific risk factors for SARS-CoV-2 infection spread was investigated among the 215 municipalities in north-eastern Italy. SARS-CoV-2 incidence was gathered fortnightly since April 1, 2020 (21 consecutive periods) to depict three indicators of virus spreading from hierarchical Bayesian maps. Eight explanatory features of the municipalities were obtained from official databases (urbanicity, population density, active population on total, hosting schools or nursing homes, proportion of commuting workers or students, and percent of > 75 years population on total). Multivariate Odds Ratios (ORs), and corresponding 95% Confidence Intervals (CIs), quantified the associations between municipality features and virus spreading. The municipalities hosting nursing homes showed an excess of positive tested cases (OR = 2.61, ever versus never, 95% CI 1.37;4.98), and displayed repeated significant excesses: OR = 5.43, 3-4 times versus 0 (95% CI 1.98;14.87) and OR = 6.10, > 5 times versus 0 (95% CI 1.60;23.30). Municipalities with an active population > 50% were linked to a unique statistical excess of cases (OR = 3.06, 1 time versus 0, 95% CI 1.43;6.57) and were inversely related to repeated statistically significant excesses (OR = 0.25, > 5 times versus 0; 95% CI 0.06;0.98). We highlighted specific municipality features that give clues about SARS-CoV-2 prevention., (© 2022. The Author(s).)

Objectives: This Monograph aims to provide the scientific community and the Regional Healthcare Service an up-to-date Atlas of mortality for the Campania Region (Southern Italy). The Atlas shows an overview of mortality through comparisons with national data and with intraregional macroareas. Maps presenting risk measures with municipal details are also provided., Materials and Methods: Both overall and cause-specific mortality data for the period 2006-2014 referred to people residing in Campania Region are analysed in this Atlas. Twenty-nine death causes (major causes and specific cancers) are studied; for each of them, it has been provided: • direct standardised rates (standard population EU 2013) referred to Italy, Campania Region, and the seven regional Local Health Units (LHUs); • standardised mortality ratios (SMRs), estimated on a regional basis, referred to every LHU; • years of life lost (number and rate) both on a regional and on LHU basis; • mortality rate trends for the period 2006-2014, including annual percentage changes (APCs) for Italy, Campania Region, and every LHU; • for every death cause, regional maps are provided also with municipal details for Relative Risks (RRs) and risk posterior probabilities (PPs) estimated through a Bayesian hierarchical model. Risk estimates are presented both crude and adjusted by socioeconomic deprivation index resulted from the 2011 Census of the Italian National Institute fo Statistics., Results: In Campania Region, standardised mortality ratios (per 100,000; IC95%) higher than the national average have been recorded for the following causes: all causes of death: M: 1,233.3 (IC95% 1,227.9-1,238.9) vs 1,093.8 (IC95% 1,092.5-1,095.1); F: 826.1 (IC95% 822.6-829.7) vs 722.8 (IC95% 721.9-732.6); digestive system diseases: M: 51.2 (IC95% 50.2-52.3) vs 44.2 (IC95% 44.0-44.5); F: 35.8 (IC95% 35.1-36.6) vs 29,2 (IC95% 29.0-29.4); circulatory system diseases: M: 493.1 (IC95% 489.6-496.8) vs 404.3 (IC95% 403.5-405.1); F: 388.5 (IC95% 386.1-390.9) vs 296.5 (IC95% 295.9-297.0); genitourinary system diseases: M: 27.2 (IC95% 26.4-28.1) vs 21.9- (IC95% 21.7-22.1); F: 18.2 (IC95% 17.7-18.7) vs 13.7- (IC95% 13.5-13.8); endocrine and metabolic diseases: M: 60.0 (IC95% 58.8-61.2) vs 43.8 (IC95% 43.5-44.0); F: 60.7 (IC95% 59.8-61.7) vs 36.6 (IC95% 36.4-36.8); myocardial infarction: M: 71.1 (IC95% 69.8-72.4) vs 60.9 (IC95% 60.6-61.2); F: 38.2 (IC95% 37.4-39.0) vs 30.2-(IC95% 30.0-30.4); diabetes: M: 52.6 (IC95% 51.5-53.8) vs 35.1 (IC95% 34.9-35.3); F: 53.8 (IC95% 52.9-54.7) vs 28.6 (IC95% 28.4-28.8). On the other hand, mortality rates comparable to or lower than the national average are observed for the remaining causes of death, with different differences for gender. Mortality for cancer causes in Campania Region presents rates higher than the rates observed at national level in males for the following causes: all cancers: 380.4 (IC95% 377.5-383.3) vs 356.5 (IC95% 355.8-357.2); lung cancer: 112.5 (IC95% 110.9/114.0) vs 93.0 (IC95% 92.6-93.3);larynx cancer: 7.6 (IC95% 7.2-8.0) vs 5.5 (IC95% 5.4-5.6);bladder cancer: 25.1 (IC95% 24.4-25.9) vs 17.3 (IC95% 17.1-17.4); in females for the following causes: liver cancer: 3.8 (IC95% 3.6-4.1) vs 3.3 (IC95% 3.2-3.4);bladder cancer:: 3.5 (IC95% 3.3-3.7) vs 3.0 (IC95% 2.9-3.0). In Campania Region, mortality rates comparable to or lower than the national average are observed for the remaining cancer causes both in females and in males. For almost all the death causes, the highest mortality rates are observed in the three LHUs of Naples (Naples centre, Naples 2 North, Naples 3 South); for some death causes, also the Province of Caserta presents the highest mortality rates. It is worth noting that these areas are characterised by the highest urbanisation and regional population density, and by exposures to possible environmental risks. Time trend analyses highlight that regional and national trends are similar for almost all the examined death causes. In Campania Region, males present decreasing trends for all-cause mortality; for respiratory system, circulatory system, and digestive system diseases; for all malignant cancers; for lung, prostate, and stomach cancers; for leukaemias. On the other hand, an increasing trend is shown for liver cancer. Trends for genitourinary system and nervous system diseases are almost unchanged; the same is for blood diseases and haemolymphopoietic system cancers. In females, there is a decreasing mortality trend for all causes, for circulatory system and digestive system diseases; for haemolymphopoietic system and stomach cancers; on the contrary, an increasing trend is highlighted for communicable diseases and lung and liver cancer, mirroring the national situation. Trends for respiratory system, genitourinary system, nervous system diseases; blood diseases; all malignant cancers; kidney and breast cancers; leukaemias are almost unchanged. The analysis of mortality data on municipal basis reported that the most excesses in mortality risk occur in the municipalities included in the area with the highest urban development of Naples and, partly, in the municipalities of the Caserta Province. The distribution of the excesses at municipal level is not homogeneous in Campania Region, but there are relevant intermunicipal differences related to the considered causes of death. This heterogeneity in the distribution of excess risk is a characteristic also of the area called Terra di fuochi (Land of fires), both for overall mortality and for mortality by gender., Conclusions: Mortality data are a valuable support to the analysis of the population health conditions. Excesses in general mortality and for some specific causes found in Campania Region vs Italy in 2006-2014 suggest that in this region there is a need to implement more strict intervention in terms both of primary prevention (for individuals and the environment) and of management of the whole care and clinical pathway of some pathologies, bearing in mind the burden of regional structural and economic factors on these excesses. The highest excesses in mortality in Campania Region have been found in the areas with the highest degree of urbanisation: this confirms the national data of a different distribution of diseases - and mortality - in the areas characterised by high urban development compared to rural areas. Finally, cause-specific mortality maps at municipal level, extended to the whole region, could enable to identify possible critical issues which may need epidemiological studies focused on possible local factors of environmental pressure.

Background: Incidence rates of thyroid cancer (TC) increased in the last decades worldwide. This study aimed to describe TC incidence in the Friuli Venezia Giulia (FVG) region, to estimate the quota of overdiagnosis, and to investigate the impact of surgery on long-term survival after TC diagnosis., Methods: TC cases reported to the FVG population-based cancer registry during 2002-2013, aged <85 years, were included. Age standardized rates (ASR) on the European population were computed, while proportion of TC overdiagnosis was estimated in comparison with expected age-specific incidence rates from published time series. Adjusted hazard ratios of death, with 95% confidence intervals, were also estimated., Results: During 2002-2013, 1701 TC cases were reported to the FVG cancer registry, with papillary TC (78.2%) as the most frequent histologic type. ASR increased from 12.4 to 16.5 in women and from 4.3 to 6.2 in men (+33.1% and +44.2%, respectively). Overdiagnosis was estimated as 79% of TC cases in women and 64% in men. Almost all TC cases (97.1%) underwent surgery, including 84.6% of women and 78.9% of men who underwent total thyroidectomy. Up to 10 years after TC diagnosis, the type of surgery did not appear to influence survival., Conclusions: This study documented an increase in TC incidence in FVG in the last decade, with overdiagnosis accounting for a large proportion of TC diagnoses and total thyroidectomy in more than 80% of cases. These findings suggest reconsidering thyroid screening practice and aggressive therapeutic strategies, as recommended by new TC guidelines.

Patient education and empowerment (PEE) is aimed at improving competence of patients during their clinical path and enabling healthcare providers with specific communication strategies. We investigated the interest of Italian Cancer Research & Care Centers (CRCI) users (patients and caregivers) in being involved in PEE activities. An anonymous questionnaire addressed to users was distributed between June 2013 and February 2014. The questionnaire gathered information on the following: health-related topics; 13 different PEE initiatives/modalities of learning already active at CRCI; personal demographic data; the willingness to be more involved in the organization of health services provided and in which context; and five preferred info-educational activities. Frequency distribution and chi-square analysis were computed. Statistical significance (p value) was set at < 0.05. A total of 875 (29%) users responded to the 3000 distributed questionnaires. The first three priorities of interest were "early diagnosis" (18%), "prevention" (17%), and "diagnosis explanation" (13%). The first three priorities on informational activity were as follows: "classes on cancer-related topics with healthcare professionals" (28%); "cancer information service" (22%); "drug information point" (7%). Forty-nine percent of the respondents stated that they would like to be involved in the organization of PEE activities, particularly caregivers and users older than 55 years of age. The preferred educational activities were "classes on cancer-related topics with healthcare professionals" and "cancer information service" on a face-to-face modality. Patients were more interested than caregivers in "prevention." The extension of PEE programs to all CRCI users into routine care will be the next step of the present research.

Objectives: To assess the accuracy of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes in identifying patients diagnosed with incident carcinoma in situ and invasive breast cancer in three Italian administrative databases., Design: A diagnostic accuracy study comparing ICD-9-CM codes for carcinoma in situ (233.0) and for invasive breast cancer (174.x) with medical chart (as a reference standard). Case definition: (1) presence of a primary nodular lesion in the breast and (2) cytological or histological documentation of cancer from a primary or metastatic site., Setting: Administrative databases from Umbria Region, Azienda Sanitaria Locale (ASL) Napoli 3 Sud (NA) and Friuli VeneziaGiulia (FVG) Region., Participants: Women with breast carcinoma in situ (n=246) or invasive breast cancer (n=384) diagnosed (in primary position) between 2012 and 2014., Outcome Measures: Sensitivity and specificity for codes 233.0 and 174.x., Results: For invasive breast cancer the sensitivities were 98% (95% CI 93% to 99%) for Umbria, 96% (95% CI 91% to 99%) for NA and 100% (95% CI 97% to 100%) for FVG. Specificities were 90% (95% CI 82% to 95%) for Umbria, 91% (95% CI 83% to 96%) for NA and 91% (95% CI 84% to 96%) for FVG.For carcinoma in situ the sensitivities were 100% (95% CI 93% to 100%) for Umbria, 100% (95% CI 95% to 100%) for NA and 100% (95% CI 96% to 100%) for FVG. Specificities were 98% (95% CI 93% to 100%) for Umbria, 86% (95% CI 78% to 92%) for NA and 90% (95% CI 82% to 95%) for FVG., Conclusions: Administrative healthcare databases from Umbria, NA and FVG are accurate in identifying hospitalised news cases of carcinoma of the breast. The proposed case definition is a powerful tool to perform research on large populations of newly diagnosed patients with breast cancer., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives To assess the accuracy of International Classification of Diseases, Ninth Revision - Clinical Modification (ICD-9-CM) codes in identifying subjects with colorectal cancer., Design: A diagnostic accuracy study comparing ICD-9-CM codes (index test) for colorectal cancers with medical chart (as a reference standard). Case ascertainment based on neoplastic lesion(s) within the colon/rectum and histological documentation from a primary or metastatic site positive for colorectal cancer., Setting: Administrative databases from the Umbria region, Azienda Sanitaria Locale (ASL) Napoli 3 Sud (NA) region and Friuli Venezia Giulia (FVG) region., Participants: We randomly selected 130 incident patients from each hospital discharge database, admitted between 2012 and 2014, having colorectal cancer ICD-9 codes located in primary position, and 94 non-cases, that is, patients having a diagnosis of cancer (ICD-9 140-239) other than colorectal cancer in primary position., Outcome Measures: Sensitivity, specificity and predictive values for 153.x code (colon cancer) and for 154.x code (rectal cancer)., Results: The positive predictive value (PPV) for colon cancer diagnoses was 80% for Umbria (95% CI 73% to 87%), 81% for NA (95% CI 73% to 88%) and 80% for FVG (95% CI 72% to 87%).The sensitivity ranged from 98% to 99%, while the specificity ranged from 78% to 80% in the three units.For rectal cancer, the PPV was 84% for Umbria (95% CI 77% to 90%), 80% for NA (95% CI 72% to 87%) and 81% for FVG (95% CI 73% to 87%). The sensitivities ranged from 98% to 100%, while the specificity estimates from 79% to 82%., Conclusions: Administrative databases in Italy can be a valuable tool for cancer surveillance as well as monitoring geographical and temporal variation of cancer practice., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: To assess the accuracy of International Classification of Diseases 9th Revision-Clinical Modification (ICD-9-CM) codes in identifying subjects with lung cancer., Design: A cross-sectional diagnostic accuracy study comparing ICD-9-CM 162.x code (index test) in primary position with medical chart (reference standard). Case ascertainment was based on the presence of a primary nodular lesion in the lung and cytological or histological documentation of cancer from a primary or metastatic site., Setting: Three operative units: administrative databases from Umbria Region (890 000 residents), ASL Napoli 3 Sud (NA) (1 170 000 residents) and Friuli Venezia Giulia (FVG) Region (1 227 000 residents)., Participants: Incident subjects with lung cancer (n=386) diagnosed in primary position between 2012 and 2014 and a population of non-cases (n=280)., Outcome Measures: Sensitivity, specificity and positive predictive value (PPV) for 162.x code., Results: 130 cases and 94 non-cases were randomly selected from each database and the corresponding medical charts were reviewed. Most of the diagnoses for lung cancer were performed in medical departments.True positive rates were high for all the three units. Sensitivity was 99% (95% CI 95% to 100%) for Umbria, 97% (95% CI 91% to 100%) for NA, and 99% (95% CI 95% to 100%) for FVG. The false positive rates were 24%, 37% and 23% for Umbria, NA and FVG, respectively. PPVs were 79% (73% to 83%)%) for Umbria, 58% (53% to 63%)%) for NA and 79% (73% to 84%)%) for FVG., Conclusions: Case ascertainment for lung cancer based on imaging or endoscopy associated with histological examination yielded an excellent sensitivity in all the three administrative databases. PPV was moderate for Umbria and FVG but lower for NA., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: To assess the accuracy of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes in identifying subjects with melanoma., Design: A diagnostic accuracy study comparing melanoma ICD-9-CM codes (index test) with medical chart (reference standard). Case ascertainment was based on neoplastic lesion of the skin and a histological diagnosis from a primary or metastatic site positive for melanoma., Setting: Administrative databases from Umbria Region, Azienda Sanitaria Locale (ASL) Napoli 3 Sud (NA) and Friuli Venezia Giulia (FVG) Region., Participants: 112, 130 and 130 cases (subjects with melanoma) were randomly selected from Umbria, NA and FVG, respectively; 94 non-cases (subjects without melanoma) were randomly selected from each unit., Outcome Measures: Sensitivity and specificity for ICD-9-CM code 172.x located in primary position., Results: The most common melanoma subtype was malignant melanoma of skin of trunk, except scrotum (ICD-9-CM code: 172.5), followed by malignant melanoma of skin of lower limb, including hip (ICD-9-CM code: 172.7). The mean age of the patients ranged from 60 to 61 years. Most of the diagnoses were performed in surgical departments.The sensitivities were 100% (95% CI 96% to 100%) for Umbria, 99% (95% CI 94% to 100%) for NA and 98% (95% CI 93% to 100%) for FVG. The specificities were 88% (95% CI 80% to 93%) for Umbria, 77% (95% CI 69% to 85%) for NA and 79% (95% CI 71% to 86%) for FVG., Conclusions: The case definition for melanoma based on clinical or instrumental diagnosis, confirmed by histological examination, showed excellent sensitivities and good specificities in the three operative units. Administrative databases from the three operative units can be used for epidemiological and outcome research of melanoma., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: To evaluate the impact of time to treatment initiation (TTI) on overall survival in patients with head-and-neck squamous cell carcinoma (HNSCC)., Materials and Methods: In the period 2003-2009, 1616 HNSCC patients were diagnosed in Friuli Venezia Giulia Region, Northeastern Italy, including 462 oral, 346 oropharyngeal, 212 hypopharyngeal, and 596 laryngeal cancers. Clinical information, including date and type of first treatment, and follow-up were retrieved from the regional Cancer Registry and a population-based health database collecting comprehensive health information on people living in the Region. Multivariate hazard ratio (HR) and confidence intervals (CI) were calculated through Cox model., Results: Overall, the median TTI was 28days, (Q1-Q3: 13-45days), but significant variations emerged according to anatomical site, cancer stage, treatment approach, and care transition to specialized centers. Five-year overall survival decreased with increasing treatment delay from 62% for TTI<30days to 39% for TTI≥90days (p<0.01). HR of death was 1.13 (95% CI: 0.92-1.39) for TTI between 45-89days, and 1.47 (1.05-2.05) for TTI≥90days. The association between TTI and poor prognosis was stronger for laryngeal cancers and early-stage HNSCCs. Further, care transition from community hospitals to specialized centers was associated to a better prognosis (HR=0.73; 95% CI: 0.60-0.88)., Conclusion: Our study findings suggest that HNSCC patients treated within 45days from diagnosis have increased survival probabilities and that early-stage patients suffered the most from treatment delay. Furthermore, care transition to specialized centers -though competitive to timely treatment- improves survival by providing the most innovative technologies and treatment approaches., (Copyright © 2017. Published by Elsevier Ltd.)

Introduction: Administrative healthcare databases are useful tools to study healthcare outcomes and to monitor the health status of a population. Patients with cancer can be identified through disease-specific codes, prescriptions and physician claims, but prior validation is required to achieve an accurate case definition. The objective of this protocol is to assess the accuracy of International Classification of Diseases Ninth Revision-Clinical Modification (ICD-9-CM) codes for breast, lung and colorectal cancers in identifying patients diagnosed with the relative disease in three Italian administrative databases., Methods and Analysis: Data from the administrative databases of Umbria Region (910,000 residents), Local Health Unit 3 of Napoli (1,170,000 residents) and Friuli--Venezia Giulia Region (1,227,000 residents) will be considered. In each administrative database, patients with the first occurrence of diagnosis of breast, lung or colorectal cancer between 2012 and 2014 will be identified using the following groups of ICD-9-CM codes in primary position: (1) 233.0 and (2) 174.x for breast cancer; (3) 162.x for lung cancer; (4) 153.x for colon cancer and (5) 154.0-154.1 and 154.8 for rectal cancer. Only incident cases will be considered, that is, excluding cases that have the same diagnosis in the 5 years (2007-2011) before the period of interest. A random sample of cases and non-cases will be selected from each administrative database and the corresponding medical charts will be assessed for validation by pairs of trained, independent reviewers. Case ascertainment within the medical charts will be based on (1) the presence of a primary nodular lesion in the breast, lung or colon-rectum, documented with imaging or endoscopy and (2) a cytological or histological documentation of cancer from a primary or metastatic site. Sensitivity and specificity with 95% CIs will be calculated., Dissemination: Study results will be disseminated widely through peer-reviewed publications and presentations at national and international conferences., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Some components of the Mediterranean diet have favourable effects on endometrial cancer, and the Mediterranean diet as a whole has been shown to have a beneficial role on various neoplasms., Methods: We analysed this issue pooling data from three case-control studies carried out between 1983 and 2006 in various Italian areas and in the Swiss Canton of Vaud. Cases were 1411 women with incident, histologically confirmed endometrial cancer, and controls were 3668 patients in hospital for acute diseases. We measured the adherence to the Mediterranean diet using a Mediterranean Diet Score (MDS), based on the nine dietary components characteristics of this diet, that is, high intake of vegetables, fruits/nuts, cereals, legumes, fish; low intake of dairy products and meat; high monounsaturated to saturated fatty acid ratio; and moderate alcohol intake. We estimated the odds ratios (OR) and the corresponding 95% confidence intervals (CI) for increasing levels of the MDS (varying from 0, no adherence, to 9, maximum adherence) using multiple logistic regression models, adjusted for major confounding factors., Results: The adjusted OR for a 6-9 components of the MDS (high adherence) compared with 0-3 (low adherence) was 0.43 (95% CI 0.34-0.56). The OR for an increment of one component of MDS diet was 0.84 (95% CI 0.80-0.88). The association was consistent in strata of various covariates, although somewhat stronger in older women, in never oral contraceptive users and in hormone-replacement therapy users., Conclusions: Our study provides evidence for a beneficial role of the Mediterranean diet on endometrial cancer risk, suggesting a favourable effect of a combination of foods rich in antioxidants, fibres, phytochemicals, and unsaturated fatty acids.

Purpose: Although a role of glycemic index (GI) and glycemic load (GL) in age-related cataract development is plausible, a few studies, all conducted in USA or Australia, provided results on this issue. The aim of the present study was to provide new original data from a Mediterranean population., Methods: We analyzed data from an Italian case-control study including 761 cases with cataract extraction and 1,522 hospital controls, frequency-matched with cases by center, sex, and age. Multivariate odds ratios (ORs) for GI and GL intakes were obtained from logistic regression models after allowance for major confounding factors, including non carbohydrate energy intake, smoking, and diabetes., Results: The ORs of cataract extraction for the highest versus the lowest tertile were 1.20 (95% confidence interval, CI 0.91-1.57) for GI and 1.57 (95% CI 1.16-2.13) for GL, with a statistically significant trend in risk for GL (p < 0.01). Results were materially unchanged when diabetics were excluded from the analysis. No heterogeneity emerged across strata of sex, age, education, smoking habits and body mass index., Conclusions: The present study supports a positive association between dietary GL and the risk of cataract extraction, independently from diabetes, and a lack of association for GI.

Background: Persons living after a cancer diagnosis represent 4% of the whole population in high-income countries. The aim of the study was to provide estimates of indicators of long-term survival and cure for 26 cancer types, presently lacking., Patients and Methods: Data on 818 902 Italian cancer patients diagnosed at age 15-74 years in 1985-2005 were included. Proportions of patients with the same death rates of the general population (cure fractions) and those of prevalent patients who were not at risk of dying as a result of cancer (cure prevalence) were calculated, using validated mixture cure models, by cancer type, sex, and age group. We also estimated complete prevalence, conditional relative survival (CRS), time to reach 5- and 10-year CRS >95%, and proportion of patients living longer than those thresholds., Results: The cure fractions ranged from >90% for patients aged <45 years with thyroid and testis cancers to <10% for liver and pancreatic cancers of all ages. Five- or 10-year CRS >95% were both reached in <10 years by patients with cancers of the stomach, colon-rectum, pancreas, corpus and cervix uteri, brain, and Hodgkin lymphoma. For breast cancer patients, 5- and 10-year CRSs reached >95% after 19 and 25 years, respectively, and in 15 and 18 years for prostate cancer patients. Five-year CRS remained <95% for >25 years after cancer diagnosis in patients with liver and larynx cancers, non-Hodgkin lymphoma, myeloma, and leukaemia. Overall, the cure prevalence was 67% for men and 77% for women. Therefore, 21% of male and 31% of female patients had already reached 5-year CRS >95%, whereas 18% and 25% had reached 10-year CRS >95%., Conclusions: A quarter of Italian cancer patients can be considered cured. This observation has a high potential impact on health planning, clinical practice, and patients' perspective., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)

Malnutrition is a significant problem among older adults living in nursing homes: Malnourished residents are at increased risk of hospitalization and mortality. Multiple factors determine malnutrition, and the extant literature has focused attention on individual factors such as aging, sex, and dependence in activities of daily living. However, little evidence is available on factors influenced by nursing care. Exploring the relationship between the nutritional status of nursing home residents and certain individual factors, including those potentially influenced by nursing care, was the aim of this cross-sectional study. A total of 186 nursing home residents was enrolled in the study; in addition, 18 nurses were involved in the data collection process. Twenty-one percent of the residents had an adequate nutritional status, 43% were at risk of malnutrition, and 36% were malnourished. Multivariate analysis revealed that those independent factors associated with malnutrition, once adjusted for age, sex, and dependence in activities of daily living, were: having had a stroke, being dependent in activities of daily living, eating half or less of food provided at mealtimes, and having their weight checked only every 3 months or longer. Nursing care projects may be effective in reducing the risk of malnutrition among nursing home residents. However, further research is needed to develop knowledge of the factors associated with malnutrition and those influenced by care delivered in nursing homes., (Copyright 2013, SLACK Incorporated.)

Aims and Background: In cancer patients, fatigue interferes with the individual's functioning and quality of life (QoL). We investigated the association between fatigue and the main QoL dimensions and mood states as well as the main sociodemographic and clinical variables., Methods: A total of 105 inpatients undergoing chemotherapy were administered the Revised Piper Fatigue Scale and the EORTC QLQ-C30 and POMS questionnaires, along with a form for collecting personal and clinical data., Results: Compared with patients reporting lower fatigue levels, patients with higher levels showed worse functioning (P <0.001) in every QoL domain (i.e., physical, role, emotional, social, cognitive functioning, pain, and general health) as well as in the assessed mood states (depression-dejection, tension-anxiety, confusion-bewilderment). Moreover, both QoL and mood states in the subgroup reporting intermediate fatigue levels were worse than those of the subgroup with lower fatigue levels (P <0.02), except for emotional functioning, general health and QoL, and tension-anxiety. In addition, fatigue was significantly associated with gender, age, education, performance status, but not with marital status, survival rate of cancer type, and current chemotherapy cycle., Conclusions: The associations observed between fatigue, the main QoL domains, and negative mood states call for further active interventions to prevent and reduce fatigue.

Some studies examined the inverse relation between nasopharyngeal carcinoma (NPC) risk and dietary fibers in endemic populations. By means of a hospital-based case-control study, we verified whether this association was also present in Italy in connection with various types of dietary fibers. Cases were 198 patients with incident, histologically confirmed, NPC admitted to major teaching and general hospitals during 1992-2008. Controls were 594 patients admitted for acute, nonneoplastic conditions to the same hospital network of cases. Information was elicited using a validated food frequency questionnaire including 78 foods, food groups, or dishes. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were estimated for quartiles of intake of different types of fiber after allowance for energy intake and other potential confounding factors. Total fiber intake was inversely related to risk of NPC (OR = 0.58 for the highest vs. the lowest quartile of intake; 95% CI: 0.34-0.96). We found an inverse association for total soluble (OR = 0.58; 95% CI: 0.35-0.96) and total insoluble fiber (OR = 0.56; 95% CI: 0.33-0.95), in particular cellulose (OR = 0.57; 95% CI: 0.33-0.96), and lignin (OR = 0.51; 95% CI: 0.31-0.85). In conclusion, this study suggests that dietary intake of soluble and insoluble fibers is inversely related to NPC risk in a nonendemic southern population.

Background: The aging of the Italian population will unavoidably lead to a growing number of persons diagnosed and living with cancer. A comprehensive description of the burden of cancer mortality among Italian elderly (65-84 years of age) in the last four decades has not been carried out yet. Cancer mortality rates were used to describe time trends between 1970-2008., Methods: Mortality counts, provided by the Italian National Institute of Statistics, were grouped according to data availability: in quinquennia from 1970-74 through 1995-99, and in 2000-03 and 2006-08 groups. Age-standardized rates (world population) were computed by calendar periods while annual percent changes (APCs) were computed for elderly and middle aged (35-64 years) people for the period 1995-2008., Results: The number of cancer deaths in elderly nearly doubled between 1970-74 (31,400 deaths/year in men, and 24,000 in women) and 2006-08 (63,000 deaths/year in men, and 42,000 in women). Overall cancer mortality rates peaked during the quinquennia 1985-89 and 1990-94 (about 1,500/100,000 in men and 680 in women) and declined thereafter. Throughout 1995-2008 cancer mortality rates decreased by -1.6%/year in men and -0.9%/year in women. These decreases were mainly driven by cancers of the stomach, bladder, prostate, and lung (APC = -3.3%, -2.7%, -2.5%, -2.2%, respectively) in men, and by cancers of the stomach, bladder, and breast (APC = -3.5%, -1.9%, -1.1%, respectively) in women. Conversely, increases in mortality rates between 1995 and 2008 were recorded for lung cancer (APC = +0.6%) in women, cutaneous melanoma (APC = +1.7%) in men, and pancreatic cancer (APC = +0.6% in men and +0.9% in women)., Conclusions: Overall favorable trends in cancer mortality were observed among Italian elderly between 1995 and 2008. Early diagnosis, improved efficacy of anti-cancer treatments and management of comorbidities are the most likely explanations of these positive observations. However, enduring preventive interventions against the most common risk factor (e.g. cigarette smoking), early diagnosis, and access to care should be reconsidered and extended to match the reductions of cancer mortality recorded in the elderly with those in the middle aged.

Aims and Background: Since emotional distress is a relevant psycho-social component of an oncological disease experience, its study is useful in multidisciplinary patient cancer care. In the present research, emotional distress together with needs during hospitalization were recorded and their associations with several socio-demographic and clinical variables were verified., Methods and Study Design: Five hundred and forty-four consecutive oncological inpatients completed two self-assessment questionnaires concerning emotional distress and needs (i.e., Hospital Anxiety and Depression Scale, Needs Evaluation Questionnaire)., Results: 27.4% and 20.8% of the enrolled patients were probable cases, respectively, for anxiety and depression; when possible cases were included the percentages raised to 52.5% and 39.3%, respectively. Furthermore, 11.9% and 20.2% of participants were simultaneously probable and possible cases for both conditions. Few differences in anxiety and depression according to socio-demographic and clinical variables were demonstrated, whereas needs seemed to be more frequently associated to them. Finally, needs also seemed to be associated with both anxiety and depression, with possible and probable cases for anxiety and depression displaying more needs than non-cases., Conclusions: The implications for both the quality of care and disease adjustment by cancer patients are discussed together with study limitations.

Introduction: Official statistics on mortality represent one of the most important indicators on the health status of a population. Cancer mortality time trends show that southern Italy is progressively losing its lower mortality gap as compared to the North of the country. The mortality contribution of this pattern at a fine geographical scale (provinces) has not been extensively studied in southern Italy., Objective: To provide a cancer mortality profile in the 23 provinces of South Italy., Design: Descriptive geographical study at population level., Setting: Cancer mortality analysis by main causes of death and gender, conducted between 1999 and 2003. We computed age-standardized rates (reference World population) (ASR) as well as standardized mortality ratios (South Italy as reference population) (SMR) to compare mortality between geographical areas., Main Outcome Measures: Mortality from all cancer causes and from major neoplasms., Results: In southern Italy, ASRs for all cancer causes (benign and malignant) were 149.3/105 in males and 81.0/105 in females. In both genders, these rates were lower than rates in Italy as a whole (-8% in males and -9% in females). Cancer mortality ASRs for liver, prostate, urinary organs, melanoma and skin, and neoplasms of lymphatic and haematopoietic tissues displayed weak, or barely any, differences between the South and Italy as a whole. Statistically significant (p<0.01) mortality excesses were observed in 7 out of 23 examined provinces, with highest frequency excesses in Naples and Caserta provinces. In males liver cancer mortality showed a SMR excess of 30- 50% in 4/23 provinces. Female breast cancer mortality displayed a 10% excess in 3/23 provinces., Conclusions: Although this analysis highlighted a lower mortality in southern Italy, as compared to Italy as a whole, seven provinces showed excesses mainly for liver and breast cancers. Current knowledge on cancer etiology explains the vast majority of such observed excesses. Further analyses will help in designing and monitoring cancer prevention and early diagnosis interventions also in South Italy.

Background: A population of breast cancer patients exists who, for various reasons, never received adjuvant post-operative tamoxifen (TAM). This study was aimed to evaluate the role of late TAM in these patients., Methods: From 1997 to 2003, patients aged 35 to 75 years, operated more than 2 years previously for monolateral breast cancer without adjuvant TAM, with no signs of metastases and no contraindication to TAM were randomized to TAM 20 mg/day orally for 2 years or follow-up alone. Events were categorized as locoregional relapse, distant metastases, metachronous breast cancer, tumours other than breast cancer and death from any causes, whichever occurred first. The sample size (197 patients per arm, plus 10% allowance) was based on the assumption of a 30% decrease in the number of events occurring at a rate of 5% annually in the 10 years following randomization. Four hundred and thirty-three patients were randomized in the study (TAM 217, follow-up 216). Patients characteristics (TAM/follow-up) included: median age 55/55 years, median time from surgery 25/25 months (range, 25-288/25-294), in situ carcinoma 18/24, oestrogen receptor (ER) positive in 75/68, negative in 70/57, unknown in 72/91 patients. Previous adjuvant treatment included chemotherapy in 131/120 and an LHRH analogue in 11/13 patients., Results: Thirty-six patients prematurely discontinued TAM after a median of 1 month, mostly because of subjective intolerance. Eighty-three events (TAM 39, follow-up 44) occurred: locoregional relapse in 10/8, distant metastases in 14/16, metachronous breast cancer in 4/10, other tumours in 11/10 patients. Less ER-positive secondary breast cancers occurred in the TAM treated patients than in follow-up patients (1 vs 10, p = 0.005). Event-free survival was similar in both groups of patients., Conclusions: This 5-year analysis revealed significantly less metachronous ER-positive breast cancers in the TAM treated patients. No other statistically significant differences have emerged thus far.

Background: The epidemiological evidence on the relation between dietary fiber intake and endometrial cancer is contradictory. Consequently, a case-control study was carried out to further investigate the role of dietary fiber intake in the etiology of endometrial cancer., Material and Methods: Cases were 454 women with incident, histologically confirmed, endometrial cancer admitted to major teaching and general hospitals. Controls were 908 women admitted for acute, non-neoplastic conditions to the same hospital network. Information on diet was elicited using a validated food frequency questionnaire., Results: Odds ratios (OR) and 95% confidence intervals (CI) for quintiles of various types of fiber were estimated after allowance for total energy intake and other potential confounding factors. Lignin intake was significantly inversely related to endometrial cancer (OR=0.6 for the highest versus the lowest quintile of intake; 95%CI: 0.4-0.9) with a slightly significant linear trend in risk (p-value=0.04)., Discussion: Data suggest the potential importance of lignin in the prevention of endometrial cancer at Italian consumption levels.

Background and Purpose: The diagnosis of cancer marks an immediate passage from a condition of health to one characterized by uncertainty, threat of death, and changes. The psychological distress is recognized as a peculiar component in the process of disease adjustment and it seems to change over time together with needs. In the present study, both psychological distress and needs were assessed twice (i.e., after the diagnosis and later during treatments) in a sample of hospitalized cancer patients., Method: Eighty-five consecutive adult patients from the same Cancer Institute in North-east Italy were involved in the research. Participants were requested to fill out both a distress (i.e., the Hospital Anxiety and Depression Scale) and needs (i.e., Needs Evaluation Questionnaire) self-reported measure within a month of diagnosis (diagnostic phase) and 3-6 months from diagnosis (therapeutic phase)., Results: In the diagnostic phase, the prevalence of probable psychological morbidity due to anxiety was 23.5% and 14.1% due to depression. When the inpatients identified as possible cases were included, the respective proportions were 56.5% and 36.5%. Progressing from diagnostic to therapeutic phase, anxiety seems to decrease, while no statistically significant difference has been found in depression levels. In both phases, the most frequently mentioned needs were the informative ones; although the decrement in time is significant only for this type of needs., Conclusion: The implications both for the quality of care and the disease adjustment by cancer patients are discussed together with study limitations.

Background: The epidemiologic evidence on dietary vitamins E and C and prostate cancer is controversial. Therefore, a case-control study was carried out to investigate the role of dietary intake of vitamins E and C in the etiology of prostate cancer., Material and Methods: Cases were 1 294 men with incident, histologically confirmed prostate cancer, admitted to the major teaching and general hospitals of five Italian areas between 1991 and 2002. Controls were 1 451 men admitted for acute, non-neoplastic conditions to the same hospitals. Information on dietary habits and nutrient intake was elicited using a validated food frequency questionnaire including 78 food groups and recipes. Odds ratios (OR) and 95% confidence intervals (CI) for increasing levels of vitamin intake were estimated after allowance for total energy intake and other confounding factors., Results: Vitamin E showed a significant inverse association with prostate cancer (OR = 0.78 for the highest versus the lowest tertile of intake, 95% CI: 0.58-0.96; p-value for trend = 0.02), whereas for vitamin C the inverse association was of borderline statistical significance (OR = 0.86; 95% CI: 0.65-1.08). Results were consistent in strata of age, body mass index, and family history of prostate cancer., Discussion: The present study shows an inverse association between dietary intake of vitamins E and prostate cancer incidence. This finding is likely to reflect the influence of diet itself since supplementation or food fortification with vitamins is rare in the Italian population.

The role of selected macronutrients, fatty acids and cholesterol in the etiology of renal cell carcinoma (RCC) was analyzed using data from a case-control study conducted in 4 Italian areas between 1992 and 2004. Cases were 767 patients with incident, histologically confirmed RCC, admitted to major teaching and general hospitals of the study areas. Controls were 1,534 subjects admitted for acute, nonneoplastic conditions to the same hospitals. Information on dietary habits and nutrient intake was elicited using a validated food frequency questionnaire including 78 food groups and recipes. Odds ratios (OR) and 95% confidence intervals (CI) for increasing levels of nutrient intake were estimated after allowance for total energy intake and other potential confounding factors. A direct association with RCC was found for starch intake (OR = 1.9 for highest versus lowest quintile of intake; 95% CI: 1.4-2.6, p-value for trend = 0.001), while an inverse association was found for fats from vegetable sources (OR = 0.6; 95% CI: 0.5-0.8; p-value for trend = 0.002), unsaturated fatty acids (OR = 0.5; 95% CI: 0.4-0.7; p-value for trend = 0.0002), and polyunsaturated fatty acids (OR = 0.5; 95% CI: 0.4-0.7; p-value for trend = 0.001). Among polyunsaturated fatty acids, linoleic acid (OR = 0.5; 95% CI: 0.4-0.7; p-value for trend = 0.0001) and linolenic acid (OR = 0.7; 95% CI: 0.5-1.0; p-value for trend = 0.01) were inversely related to RCC. When 6 major macronutrients were included in the same model, the adverse effect of high intake of starch remained statistically significant, together with the protective effect of polyunsaturated fatty acids. Results were consistent in strata of age, body mass index, treated hypertension, energy intake, stage and family history of RCC., ((c) 2008 Wiley-Liss, Inc.)

A retrospective comparative study was conducted in Italy to determine whether the risk of accidental falls is the same in acute care hospitals as in nursing homes. Accidental falls were significantly related to women older than 80 years and to a hospital stay 10 days or longer, with an increased risk related to stroke, arterial hypertension, and a Norton Scale score greater than 15. Prevention strategies need to be based on the context and specific intrinsic and extrinsic factors influencing the risk of falls in elderly patients.

To investigate the association between non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), and exposure to childhood diseases, we analyzed an Italian case-control study that included 225 histologically-confirmed incident cases of NHL, 62 HL cases, and 504 controls. After adjusting for confounding factors, all examined childhood diseases were negatively associated with HL. Measles was negatively associated with NHL, particularly follicular B-cell NHL. Our findings provide additional support to the hypothesis that infections by most common childhood pathogens may protect against HL or, at least, be correlated with some other early exposure, which may lower the risk of HL in adulthood. In addition, our study shows that measles may provide a protective effect against NHL.

Background: Breast cancer in men is an infrequent occurrence, accounting for approximately 1% of all breast tumors with an incidence of about 1:100,000. The relative rarity of male breast cancer (MBC) limits our understanding of the epidemiologic, genetic and clinical features of this tumor., Methods: From 1997 to 2003, 10 MBC patients were referred to our Institute for genetic counselling and BRCA1/2 testing. Here we report on the genetic and phenotypic characterization of 10 families with MBC from the North East of Italy. In particular, we wished to assess the occurrence of specific cancer types in relatives of MBC probands in families with and without BRCA2 predisposing mutations. Moreover, families with recurrent BRCA2 mutations were also characterized by haplotype analysis using 5 BRCA2-linked dinucleotide repeat markers and 8 intragenic BRCA2 polymorphisms., Results: Two pathogenic mutations in the BRCA2 gene were observed: the 9106C>T (Q2960X) and the IVS16-2A>G (splicing) mutations, each in 2 cases. A BRCA1 mutation of uncertain significance 4590C>G (P1491A) was also observed. In families with BRCA2 mutations, female breast cancer was more frequent in the first and second-degree relatives compared to the families with wild type BRCA1/2 (31.9% vs. 8.0% p = 0.001). Reconstruction of the chromosome phasing in three families and the analysis of three isolated cases with the IVS16-2A>G BRCA2 mutation identified the same haplotype associated with MBC, supporting the possibility that this founder mutation previously detected in Slovenian families is also present in the North East of our Country. Moreover, analysis of one family with the 9106C>T BRCA2 mutation allowed the identification of common haplotypes for both microsatellite and intragenic polymorphisms segregating with the mutation. Three isolated cases with the same mutation shared the same intragenic polymorphisms and three 5' microsatellite markers, but showed a different haplotype for 3' markers, which were common to all three cases., Conclusion: The 9106C>T and the IVS16-2A>G mutations constitute recurrent BRCA2 mutations in MBC cases from the North-East of Italy and may be associated with a founder effect. Knowledge of these two recurrent BRCA2 mutations predisposing to MBC may facilitate the analyses aimed at the identification of mutation carriers in our geographic area.

Aims and Background: After the first adjuvant study on adult soft tissue sarcomas was concluded, the participating institutions continued to select and treat patients according to that protocol. The aim of this study was to test the protocol reproducibility when applied as a standard practice., Methods: A call for retrospective data was launched in June 1999 (self-referral of consecutive unregistered patients); thereafter, a prospective follow-up was performed. The treatment regimen consisted of epirubicin (60 mg/m2 days 1 and 2), ifosfamide (3 g/m2/die for 3 days) and equimolar doses of 6-mercapto-ethansulfonate (MESNA), with 300 microg G-CSF administered subcutaneously from day +8 until recovery, every 3 weeks for a total of 5 cycles., Results: From November 1996 to June 1999, 55 high-risk, adult patients were treated. The average median dose intensity was 89% of the planned program. Grade 3-4 toxicities were leukopenia (49%), thrombocytopenia (14%), transfusion requiring anemia in 7 patients (16%), and alopecia in all patients (100%). After a median follow-up of 70 months, 23 patients (41.8%) relapsed and 19 died. Median disease-free, local disease-free and overall survival rates have not yet been reached. The disease-free survival rates at 2 and 4 years were 73% and 57%, respectively; the corresponding overall survival rates were 91% and 70%, respectively., Conclusions: The feasibility and reproducibility of the original protocol were confirmed, since disease-specific overall survival and disease-free survival rates at the same period of observation and with the same prolonged follow-up did not differ.

We investigated EBV viremia in matched serum and peripheral blood mononuclear cells (PBMCs) from one of the largest Italian cohort of Undifferentiated Carcinoma of Nasopharyngeal Type (UCNT) patients (N=34). By using a LMP-1 real-time PCR assay, we found that EBV DNA detection rate was 74% (median 8417 copies/ml) and 24% (median 164 copies/10(6)cells) on serum and PBMCs, respectively. Significantly higher serum EBV DNA levels were detected in patients with advanced UCNT (nodal stage N2 versus N0-1 and N3 versus N0-1, P=0.03 and 0.018; overall stage IV versus I-II, P=0.03). During the follow-up, there was also a statistically significant difference of EBV DNA viral load between patients with and without clinical relapse (P=0.008). We concluded that serum EBV DNA reflects the biological activity of the UCNT and may be a prognostic factor also in a low-incidence region.

Purpose: Cytokines such as IL-10 and IL-18 seem to be involved in the inflammatory response of undifferentiated carcinoma of nasopharyngeal type (UCNT). The aim of this study was to evaluate the correlation between functional single nucleotide polymorphisms (SNPs) in the promoter region of IL-10 and IL-18 genes and the virological and clinical characteristics in a large case series of Caucasian patients suffering from UCNT, a tumor regularly associated with the Epstein Barr Virus (EBV)., Methods: Eighty-nine patients with histologically confirmed UCNT and 130 healthy donors were included in our study. DNA was examined for the polymorphisms of IL-10 gene at positions -1082, -819, -592 by direct sequencing and IL-18 gene at position -607 and -137 by allele-specific PCR. EBV DNA serum viremia was evaluated by QC-PCR., Results: The distributions of the IL-10 and IL-18 genetic variants were not different between UCNT patients and healthy controls. The frequency of IL-10 -1082G allele, which is associated with high IL-10 expression, showed a nearly statistically significant increase in UCNT patients EBV DNA-negative as compared to healthy controls (OR=3.3 95% CI: 1.2-9.8). Subjects with C/C or C/G combined IL-18 genotypes showed an increased risk of being with Stages III-IV (OR=2.1 95% CI: 1.2-6.6)., Conclusion: This study was performed to improve the definition of the pathogenetic factors implicated in UCNT by addressing the correlation between cytokine polymorphisms and clinical parameters. This is the first study investigating the possible role of the IL-18 and IL-10 polymorphisms in the development and outcome of UCNT. In our genetic analysis there is no evidence for involvement of IL-10 promoter polymorphisms alone in the genetic predisposition to this tumor. On the other hand, IL18 genetic variants may represent a genetic risk factor for tumor aggressiveness.

Objective: To describe the global impact of infectious diseases on mortality in Italy from 1969 to 1999., Design: Statistical analysis of routinely collected mortality data, using a revised definition of infectious causes of death based on target organs., Setting: The present paper summarizes time trends of infectious disease mortality widely discussed in the Atlas "30 Anni di Malattie Infettive in Italia: Atlante di Mortalità"., Main Outcome Measures: Age standardized mortality rates (/100,000); standardized mortality ratios (SMR); percentage of deaths attributable to infectious diseases., Results: Apart from HIV infection and AIDS, infectious diseases were responsible of 1.7% of the overall mortality that occurred in Italy in the study period: 57.5% of such deaths were not included in the ICD8 and ICD9 codes for infectious diseases. The mortality for all infectious diseases showed a very strong downward trend up to 1994, (with a 6-fold decline). Thereafter, a slight increase in deaths for septicaemias, heart infections and hepatitis was recorded. Over time, an increasing proportions of deaths due to infections occurred in the elderly (i. e., > or = 65 years of age), from 48.1% in 1969-1979 to 77.3% in 1990-1999. Mortality rates were consistently higher in men than in women, and showed a substantial geographic heterogeneity. In newborns, from 1969 thru 1999 mortality rates declined 10-fold all over the country, but an inverse north-south geographic gradient persisted during the whole study period. The spread of HIV infection and AIDS epidemic in the first '80s dramatically interrupted the downward trend in infectious disease mortality outlined above. Between 1993 and 1996, HIV/AIDS was the main cause of death among Italian men aged 30 to 39 years., Conclusions: This statistical analysis allowed to better quantify the impact of infectious diseases on overall mortality in Italy. Observed time trends were in accordance to the picture recorded in other western Countries, whereas the higher newborn mortality in southern Italy reflects the persistence of geographical inequalities in the health care organization.

Our research aimed to describe infectious disease mortality in Italy between 1969 and 1999, with particular emphasis on sex, age, and geographic differences. Using mortality data provided by the Italian Central Institute for Statistics (ISTAT), we evaluated all codes of the ICD8 and ICD9 classifications to identify each cause of death attributable to infectious agents. Deaths for HIV/AIDS were excluded. Infectious diseases accounted for 1.7% of overall mortality between 1969-1999, and our approach identified 57.5% of all deaths from infections not included in the ICD8 and ICD9 infectious disease codes. Up to 1994, the mortality for all infectious diseases showed a very strong downward trend, with a 6-fold decline. This trend levelled off in 1995-1999, mainly due to increasing deaths due to septicaemias, heart infections and hepatitis. An increasing proportion of deaths due to infectious diseases occurred in the elderly, from 48.1% in 1969-1979 to 77.3% in 1990-1999. Mortality rates were consistently higher in men than in women and showed a substantial geographic heterogeneity. In the newborn, mortality rates declined 10-fold and an inverse north-south geographic gradient persisted during the study period. This exhaustive methodological approach to identifying infectious causes of deaths allows us to better define the burden of infections on mortality and register downward trends similar to those found in other industrialized countries.

Background: Nasopharyngeal carcinoma (NPC) is frequently associated with Epstein-Barr virus (EBV), but little is known about the EBV DNA prevalence on peripheral blood in Western Countries, where the tumour is not endemic and its incidence is low., Objectives: To set up and evaluate an internally controlled qualitative polymerase chain reaction (PCR) followed by quantitative competitive PCR for the detection of EBV DNA in clinical specimens. To investigate whether EBV DNA load in peripheral blood was a consistent feature of Italian NPC patients., Materials and Methods: A PCR assay based on latent membrane protein 2A (LMP2A) sequence amplification was chosen. Best assay conditions, sensitivity and reproducibility were determined. Sixty-four sera and 63 plasma from an Italian cohort of 39 NPC patients were analyzed. Samples from 5 patients followed up after radiotherapy were also assayed. Qualitative and quantitative beta-globin amplification was performed in parallel in order to provide an independent control for amplification competence of DNA and to investigate whether EBV DNA levels could be due to intracellular EBV viral genomes from cells lysed during plasma/serum collection., Results: Twenty-five patients had undifferentiated carcinoma (UC) and 14 squamous cell carcinoma (SCC). EBV DNA has been quantified in 58 and 9% of the UC and SCC cases, respectively. No statistically significative differences were observed between the EBV DNA levels (469 vs 750 copies/ml, P=0.16) and prevalence (64 vs 57%, chi2(1)=0.22, P=0.64) in plasma and serum samples. Increased EBV viremia was found in patients with considerable extension of the primary tumour (172 vs 2250 copies/ml, low vs high tumour burden). Three UC subjects, which had detectable pre-treatment EBV DNA levels, became negative after radiotherapy. Clinical examination revealed that all had complete tumour regression., Conclusions: These PCR procedures allow an accurate and reproducible estimation of plasma/serum EBV DNA load in NPC patients living in non endemic areas, being strictly associated with UC WHO III and with tumour severity.

Locally advanced carcinomas are considered for comparison with non-neoplastic entities and other gastric and non-gastric tumor types. How can primary gastric carcinomas be pathologically distinguished from mimics and metastatic carcinomas? And carcinomas of the cardia from Barrett adenocarcinomas? And undifferentiated gastric carcinomas from other undifferentiated neoplasms? To answer these questions, topographic, morphologic and immunohistochemical distinctive features are illustrated. Moreover, a pathological "excursus" on the most frequent neoplasms of the stomach is provided along with epidemiological data concerning the incidence, survival and mortality rates of gastric carcinomas in Italy in the 1990s. Pathologic aspects and macro-microscopic appearances of carcinomas are described according to the most recent classification systems. A brief commentary is given on the new TNM staging formulation for gastric carcinomas. A correct pathological diagnosis of gastric carcinoma can be made in the vast majority of cases; however, some diagnostic uncertainties still exist in individual cases.

Objective: To provide information on the effects of alcohol and tobacco on laryngeal cancer and its subsites., Methods: This was a case-control study conducted between 1992 and 2000 in northern Italy and Switzerland. A total of 527 cases of incident squamous-cell carcinoma of the larynx and 1297 hospital controls frequency-matched with cases on age, sex, and area of residence were included. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using multiple logistic regression., Results: In comparison with never smokers, ORs were 19.8 for current smokers and 7.0 for ex-smokers. The risk increased in relation to the number of cigarettes (OR = 42.9 for > or = 25 cigarettes/day) and for duration of smoking (OR = 37.2 for > or = 40 years). For alcohol, the risk increased in relation to number of drinks (OR = 5.9 for > or = 56 drinks per week). Combined alcohol and tobacco consumption showed a multiplicative (OR = 177) rather than an additive risk. For current smokers and current drinkers the risk was higher for supraglottis (ORs 54.9 and 2.6, respectively) than for glottis (ORs 7.4 and 1.8) and others subsites (ORs 10.9 and 1.9)., Conclusions: Our study shows that both cigarette smoking and alcohol drinking are independent risk factors for laryngeal cancer. Heavy consumption of alcohol and cigarettes determined a multiplicative risk increase, possibly suggesting biological synergy.

Aims and Background: Until 1998 there was opportunistic screening in Friuli Venezia Giulia (FVG). Beginning in 1999, formal screening efforts were organized. The regional cancer registry was established in 1998, and data on incidence was collected for the period 1995-98. The scope of this study is to provide baseline data on the incidence of invasive cervical cancer in FVG for further examination of trends in incidence and of the effectiveness of screening efforts., Methods: Data from the regional cancer registry database was examined and linked with data from the regional pap smear screening database., Results: The incidence of cervical cancer in FVG was 8.6 per 100,000. Most women were diagnosed in stages I and II. Most cervical cancers (80%) were squamous cell. Opportunistic screening in FVG reached 39.8% of the total female population. Analysis by local health unit showed heterogeneous data., Conclusions: FVG has one of the highest incidence rates of cervical cancer in Italy. Approximately 1/3 of the diagnoses were in women over the age of 65. Pap smear screening prior to the formal program covered a low percentage of the female population. Screening efforts in the future should focus on screening coverage in the older female population.

The CAG repeat (CAGn) present in the N-terminal region of the androgen receptor (AR) inversely correlates with AR transactivation activity. The aim of this study was to investigate whether polymorphic variation in the CAGn length is associated with the risk of developing ovarian cancer. Using a case-control study design 121 women with histologically confirmed ovarian cancer and 100 controls (healthy women) were genotyped for AR-CAG length. No marked difference in the mean length of CAGn was observed between ovarian cancer patients and controls. However, when considering patients with positive personal or family history of tumor (PPFHT), the mean lengths of the long allele, the short allele and the average of the 2 alleles were longer than in the controls. Odds ratios (OR) and their corresponding 95% confidence intervals (CI) were computed after allowance for age. We observed an increase in the risk of ovarian cancer, in terms of OR, in women with CAGn >or=22 (OR=2.17, 95% CI:1.10-4.27). The increase of relative risk was particularly high in women with CAGn >or=22 belonging to the PPFHT group: OR=3.52 (95% CI 1.18-10.47). We also found a statistically significant trend (chi2 trend=4.91; p=0.03) towards an increased risk of ovarian cancer with increasing CAGn length (from or=26). Again, a strong association between increase in CAGn and risk of ovarian cancer was observed in PPFHT patients (chi2 trend=6.38; p=0.01). The results suggest that AR-CAG repeat length could play a role as modifier of the ovarian cancer risk conferred by highly penetrant genes rather than itself conferring a low risk.

Aims: The aim of this study was to report prognostic factors, end-points of local recurrence, distant recurrence, post-metastasis survival, and overall survival in a cohort of patients with soft tissue sarcomas., Methods: We analysed a database of 395 patients affected by primary soft tissue sarcomas of various primary sites, treated and followed up at the Centro di Riferimento Oncologico, Aviano, Italy from January 1985 to January 1997., Results: Grade, size, stage, surgical margins, distant metastasis, age, sex, performance status, and haemoglobin value were significant for overall survival. Histology, grade, stage, and surgical margins were significant for local recurrence. Grade, size, and stage, were significant for distant recurrence; and surgical margin was significant variable for post-metastasis survival., Conclusions: Grade, size, and TNM stage (UICC/AJCC) have stronger prognostic significance for overall survival and distant recurrence than for local relapse. Positive surgical margins are the main predictors for local relapse. Age was the most consistent adverse independent prognostic factor for survival., (Copyright Harcourt Publishers Limited.)

Between 1992 and 1997 we conducted a case-control study of oesophageal cancer in 3 areas of northern Italy. Cases were 304 patients (29 women), ages 39-77 years (median age 60 years), with a first incident squamous-cell carcinoma (SCC) of the oesophagus. Controls were 743 patients (150 women), ages 35-77 years (median age 60 years), admitted for acute illnesses, unrelated to tobacco and alcohol, to major hospitals of the areas under surveillance. We derived estimates of daily dietary intake of 6 macronutrients, cholesterol, and 20 micronutrients or minerals from a validated food-frequency questionnaire, including 78 food groups and recipes and 15 questions on individual eating patterns. After allowance for age, gender, area of residence, education, body mass index, physical activity, smoking habit, alcohol consumption and energy intake, most micronutrients were inversely associated with oesophageal SCC risk. Highly significant associations emerged for monounsaturated fatty acids [odds ratio (OR) in highest vs. lowest intake quintile = 0.5]; carotene (OR = 0.3); lutein + zeaxanthin (OR = 0.4); vitamin C (OR = 0.4); and niacin (OR = 0.5). Only retinol appeared to be positively related to risk (OR = 1.9). The effect of the above nutrients, expressed as ORs, appeared to be similar in non-smokers and smokers, and non/light drinkers and heavy drinkers., (Copyright 2000 Wiley-Liss, Inc.)

Although invasive cervical cancer (ICC) has been included among the AIDS-defining conditions since 1993, it remains controversial whether HIV infection increases the risk of developing such neoplasm. In this study, ICC risk was longitudinally investigated among 1,340 HIV-positive intravenous drug user (IDU), 811 HIV-negative IDU, and 801 HIV-positive heterosexual women. These women, aged 15-49 years, were followed up at the Italian HIV Seroconverter Study, at the San Patrignano Community (Rimini, North Italy), and in South-eastern France (the DMI-2 study). The number of observed cases of ICC was compared with the expected one, based on ICC incidence rates among women of the same age in the general population of Italy or France, and standardized incidence ratios (SIR) were computed; 9,070 person-years of observation were accumulated among HIV-positive women and 2,310 among HIV-negative ones. Ten cases of ICC were diagnosed among HIV-positive women (SIR = 12.8): ICC risk was apparently higher among HIV-positive IDU (SIR = 16.7) than among heterosexual women (SIR = 6.7). No cases of ICC were diagnosed among HIV-negative IDU women admitted to the San Patrignano Community (0.15 cases were expected). Our findings confirm previous suggestions showing an increased risk of ICC among HIV-infected women and have important implications at the individual and public health levels.

Aims and Background: The risk for several cancers is higher in urban than in rural areas. The gradient has seldom been studied in southern Europe., Patients and Methods: The geographical pattern of mortality for different cancers and all causes was studied in the Campania Region (about 5.6 million inhabitants), whose largest town is Naples. The key variables were residence in urban/rural and coastal/inland municipalities. Relative risks of death and corresponding 95% confidence intervals by residence were evaluated by means of Poisson log-linear regression models., Results: Significantly increased mortality rates in urban compared to rural municipalities were found for several cancer causes of death. In particular, in both sexes, excesses in the order of 30-50% were observed for tobacco-related neoplasms (i.e., larynx, lung, and bladder) and cancers of the intestine, liver, brain, multiple myeloma and non-Hodgkin's lymphoma, in addition to all-cancer, and all-cause mortality. In females, specific excesses were also noticed for cancer of the gallbladder, pancreas, breast and uterus (corpus and cervix). Conversely, significantly decreased mortality rates in urban with respect to rural municipalities were observed for cancer of the oral cavity and pharynx in males. Coastal location and degree of urbanization were strongly correlated, thus showing similar associations with most causes of death. However, a significant excess of cancer of the pleura in males was restricted to coastal municipalities., Conclusions: Anti-smoking campaigns, sanitation improvements, hepatitis B vaccination, and a decrease in obesity emerge as high priorities with respect to cancer control strategies in the Campania Region, particularly in overpopulated, underprivileged urban areas.

Osteoporosis is a major health issue in post-menopausal women on account of the association between low bone mineral density and fractures. A role of physical activity in the prevention and treatment of low bone mineral density is possible but still unclear. The relationship between low spine bone mineral density measured by means of dual photon absorptiometry at lumbar spines, and levels of past and recent physical activity has been assessed by means of a population-based screening study carried out on 1373 women (age 40-64 years) in the North-East of Italy. Physical activity at work and in leisure time was investigated for three specific periods of life: at age 12, between 15 and 19 years (during bone formative years), and in the recent years prior to the interview (30-39 or 50-59 years). Data were analysed comparing low versus high bone mineral density tertile (i.e., 458 and 461 women, respectively), after controlling for other known contributory factors in the development of osteoporosis. A positive association emerged with leisure time physical activity, with significant trends at age 15-19 (odds ratio (OR) for low versus high tertile of leisure time activity: 1.4, 95% confidence interval (CI): 0.8-2.4) and at most recent age (OR: 1.7, 95% CI: 1.1-2.6). Risk trends with occupational physical activity were less clear and non-statistically significant. The present Southern European cross-sectional study lends further support to the possibility that past and recent physical activity helps increasing bone mineral density in middle-aged women. Although the most beneficial type and intensity level of exercise has yet to be determined, the present results provide further evidence that participation in even moderate exercise programs should be encouraged.

The incidence of liver cancer appears lower in Europe and the USA and it is often looked upon as a problem in developing countries. Liver cancer has two main risk factors: the abuse of alcohol and the elevated prevalence of hepatitis B and C viruses. In Italy the first one is mainly present in the North and the second one in Southern less developed areas. Our study evaluates the relationship between living in urban and suburban zones in South of Italy in conditions of overcrowding, poor health services and high incidence of hepatitis and liver cancer.

We studied the determinants of low bone mineral density, using data from a population-based screening program of osteoporosis carried out among 1,373 women (age 40-64 years) in the province of Pordenone, Italy, by means of dual photon absorptiometry of the lumbar spine. Menopause had a major effect on bone mineral density. Age had little influence before menopause. In multivariate linear regression analyses, weight was the strongest predictor of bone mineral density in pre- as well as postmenopausal women. After the inclusion in a single model of a term for current weight, weight at ages 12 and 30 years explained some additional variance, whereas high waist-to-hip ratio (an indicator of central adiposity) had no influence. Smoking 15 or more cigarettes per day entailed a small increased risk of osteoporosis, but this effect, independent of weight, appeared to be restricted to premenopausal women. No food or micronutrient that we examined was predictive of bone mineral density, nor was coffee or alcoholic beverage intake.