Search

The quantitative evaluation of human herpesvirus 8 (HHV8) DNA is not well described in the clinical management of HHV8-related lymphoproliferative diseases.To evaluate and to compare HHV8 viral load in different blood compartments from patients with multicentric Castleman's disease (MCD), primary effusion lymphoma (PEL) and HHV8-associated solid lymphoma (SLY) and to establish which clinical sample would be preferable for HHV8 DNA testing.We assessed HHV8 DNA in plasma and peripheral blood mononuclear cells (PBMCs) paired samples from 7 PEL, 8 MCD, 2 SLY HIV+ patients at the diagnosis and during the course of the illness by using a real time PCR assay.HHV8 viremia was always detectable at diagnosis. HHV8 DNA levels were correlated in matched pairs of samples at diagnosis and during follow-up (Spearman correlation coefficient: r=0.83, p0.001 and r=0.73, p0.001, respectively). The performance characteristics of the PCR assay with both materials did not show disparity by the analysis of the receiver operating characteristic (ROC) curve (X(1)(2)=0.50; p=0.48).Plasma or PBMCs are both adequate samples for HHV8 DNA quantification and Real time PCR provides a reliable method to estimate viral replication in patients with HHV8-related lymphoproliferations, where HHV8 viral load is a consistent feature.

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.

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% Cl: 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% Cl: 0.4-0.7; p-value for trend = 0.0002), and polyunsaturated fatty acids (OR = 0.5; 95% Cl: 0.40.7; 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.

The effect of various patient and tumor characteristics were evaluated in 378 laryngeal carcinomas treated only surgically between November 1974 and December 1987 at the Ear, Nose and Throat Clinic of Cagliari Medical University in South Sardinia. The overall three-year survival rate was 68%, the five-year survival rate was 61% (approximate 95% confidence interval (CI), 54-68%), and then a plateau seemed to emerge, with the ten-year survival rate being 51%. Tumor ulceration exerted a strong influence on survival: patients with ulcerated tumors had a twofold (95% CI, 1.4-2.9%) higher death rates. Conversely, the influence of tumor site and type of operation was not statistically significant in the multivariate analysis. A median delay in diagnosis of 4 months was found, with 30% of patients reporting an interval longer than 6 months between first symptoms and referral to a physician; overall, however, the influence of delay in diagnosis on survival rate was not significant. Dysphonia seemed to be the symptom less promptly recognized by the patient.

Epstein-Barr virus (EBV)-associatedundifferentiatedcarcinoma of thenasopharyngealtype (UCNT) is highly prevalent in southeast China, where immunoglobulin A (IgA) antibodies to viral capsid antigen and early antigen (EA) represent important markers, routinely used to assist in diagnosing this malignancy. Our study aimed at determining the EBV serological profiles of 78 UCNT patients from Italy, an area of nonendemicity for this tumor, using different assays specific for both lytic and latent EBV antigens. Serum IgA against both EA and EBNA1 and IgG and IgA to the latent membrane protein 1 (LMP1), to EA, and to the EBV transactivator ZEBRA protein were assessed. These serological responses were then evaluated according to the clinicopathologic parameters at diagnosis. The sensitivities of the IgG assays were 37.7% for LMP1, 73.6% for EA, and 61.0% for ZEBRA. EA/EBNA1 IgA reactivity was 84.4%, and a high association (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.7 to 4.0) with UCNT was observed. When EBV serological reactivities were analyzed according to the tumor, node, and metastasis staging system (TNM), a statistically significant association was found between N stage and IgG antibody rates for EA (OR, 3.6; 95% CI, 1.2 to 10.9) and ZEBRA (OR, 2.6; 95% CI, 1.2 to 5.5) and between M stage and IgG antibody rates for ZEBRA (OR, 7.1; 95% CI, 3.2 to 16.0) and LMP1 (OR, 14.0; 95% CI, 1.8 to 110.9). Our results show that no single serological marker allows the detection of all UCNT cases. EA/EBNA1 IgA represents a reliable marker for diagnosis, with a high predictive value also in areas where UCNT is not endemic, such as Italy. The analysis of serological results according to TNM classification is consistent with a progressive impairment of humoral immune response to EBV as the disease advances and may be used to improve the accuracy of diagnosis.

Arrays are one of the technologies able to detect autoantibodies by measuring simultaneously many thousands of markers from a unique biological sample. The main purpose of a diagnostic test is making an early and accurate diagnosis. From a statistical point of view, multiple testing increases the probability of false positive and false negative results. Some correction methods are available to account for this problem for instance family-wise error rate or false discovery rate. From an ethical point of view, the decision to accept or decline a test not requested has to be made autonomously. Some people may seek clarification about tests and implications of their choices. A scarcity of proven measures to reduce mortality has to be considered too. Reasons may also include avoidance of psychological harm or anxiety. Moreover, protection of confidentiality and privacy has to be respected. In conclusion, the fact that testing is optional and that surveillance advice can be offered on the basis of risk alone without a test should be discussed in the consultation. The implication of a positive test result should be discussed to make a decision about the degree to which early treatment of the condition is better than late (or no) treatment.

The effects of CD34 mobilization with chemotherapy and G-CSF administration were evaluated in 13 HIV-positive patients with relapsed lymphomas and low CD4 counts. After mobilization, CD4+ cells increased significantly while HIV-RNA and integrated HIV-DNA showed no increases. G-CSF led to an increase of CD4+ cells with limited effects on HIV replication.

A population-based serosurvey of Human Herpesvirus type 8 (HHV8) in Västerbotten County, an area of Northern Sweden with high incidence of Kaposi's Sarcoma, was conducted. Serum samples from an age- and sex-stratified random sample of 520 subjects (260 men and 260 women) participating in a population-based biobanking project were tested for antibodies against HHV8, using a sensitive indirect immunofluorescence assay to latent and lytic HHV8 antigens. Buffy coat DNA was also analyzed for viral DNA using real time PCR assay. HHV8 DNA was not detectable in any one of the buffy coat samples. Eighty-four subjects (16.2%) were HHV8 seropositive, 14.4% for the lytic HHV8 antigen, and 1.7% for the latent HHV8 antigen. HHV8 seroprevalences were not associated significantly with sex or age. HHV8 seropositivity was more common among smokers (OR: 1.95, 95% CI: 1.02-3.75), but was less common among consumers of wine and spirits (OR: 0.44, 95% CI: 0.25-0.77 and OR: 0.50, 95% CI: 0.26-0.95, respectively). In summary, HHV8 has an intermediate high and stable seroprevalence rate in Northern Sweden, but environmental determinants that can explain the viral distribution were not found.

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.

Background The clinical and pathological characteristics and the clinical course of patients with breast cancer and BRCA 1–2 mutation are poorly known. Methods From 1997, patients with breast cancer and a family history of breast or ovarian cancer were offered BRCA testing. The clinical and pathological features of patients with known BRCA status were retrospectively assessed and comparisons were made between cancers arising in BRCA positive and BRCA wild type (WT) patients respectively. Type of treatment, pattern of relapse, event (local relapse, contralateral breast cancer, metastases) free and overall survival were also compared in the two groups. Out of the 210 patients tested, 125 had been treated and followed-up at our Institution and were evaluated in this study. Results BRCA positive patients tended to be more often premenopausal (79% vs 65%) and to have positive lymphnodes (63% vs 49%), poorly differentiated tumours (76% vs 40% – p = 0.002 at univariate analysis, not significant at multivariate analysis) and negative estrogen receptors (43% vs 29%). Treatment was not different in the two groups. In the 86 BRCA-WT patients, the first event was a local relapse in 3 (3%), metachronous contralateral breast cancer in 7 (8%) and distant metastases in 16 (19%). In the 39 BRCA positive patients, the corresponding figures were 3 (8%), 8 (21%) and 3 (8%). There was no difference in event free survival, with a median of 180 months in both groups of patients. At 20 years, projected survival was 85% for BRCA positive patients and 55% for BRCA-WT, but this difference was not statistically significant. Conclusion Although BRCA positive patients have more frequently negative prognostic factors, their prognosis appears to be equal to or better than in patients with BRCA-WT.

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.

To describe the global impact of infectious diseases on mortality in Italy from 1969 to 1999.Statistical analysis of routinely collected mortality data, using a revised definition of infectious causes of death based on target organs.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".Age standardized mortality rates (/100,000); standardized mortality ratios (SMR); percentage of deaths attributable to infectious diseases.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.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.

Summary. Passenger leucocytes transfused with allogenic blood are responsible for potential adverse effects. The impact of pre-storage leucodepletion (in-line filtration) of all whole blood units on transfusion reaction rate among patients suffering from cancer was retrospectively studied, comparing all reactions following red blood cell (RBC) transfusions during 2 years of pre-storage vs. 2 years of selective (bedside) leucodepletion. During selective leucodepletion, 5165 RBC units – of which 2745 were bedside filtered units– were transfused to 866 patients. Twenty-eight reactions were recorded: 22 (15 in the bedside group) febrile non-haemolytic transfusion reactions (FNHTR) and six allergic reactions (five in the bedside group). The overall percentage of reactions was 0·54 (0·76 for bedside) and 0·42 for FNHTR (0·54 for bedside). During pre-storage leucodepletion, 4116 RBC units were transfused to 841 patients. Eleven reactions were recorded: four FNHTR and seven allergic reactions (urticaria). The percentage of reactions for transfused RBC units was 0·26 (0·09 for FNHTR). Comparison between pre-storage filtration and bedside filtration with regard to FNHTR showed an odds ratio of 2·80 (95% confidence interval = 0·83–14·87) for bedside filtration. The study suggests that, for transfused patients affected by cancer, pre-storage leucodepletion is more effective than selective (bedside) filtration in reducing the incidence of transfusion reactions (FNHTR).

Celiac disease (CD) may be found in association with other autoimmune diseases. We investigated the relation between autoimmune hepatitis (AIH) and CD by assessing the prevalence of IgA and IgG anti‐tissue transglutaminase (tTG) antibodies in AIH, and by verifying whether the findings were associated with clinical and histological features of CD. Forty‐seven consecutive patients with AIH (type I: n = 39; type II: n = 8) were studied. One hundred patients with chronic hepatitis C, and 120 healthy blood donors were also studied as controls. We analyzed sera for the presence of IgA and IgG anti‐tTG antibodies using a specific human recombinant tTG immunoenzymatic assay. Anti‐tTG positive patients and controls were further tested for anti‐endomysium antibodies (EMA) and HLA typing, and those found positive by either of these tests underwent duodenal biopsy to confirm a possible diagnosis of CD. Three of the 47 AIH patients (6.4%) were positive for IgA anti‐tTG and EMA antibodies, and were subsequently confirmed to be affected with CD by small‐bowel biopsy findings. No IgG anti‐tTG positivity was found in the AIH patients. None of the controls were positive for IgA anti‐tTG, and only one with chronic hepatitis C had a low positive reaction for IgG anti‐tTG, which resulted as a false positive. The crude prevalence rate of CD in AIH was 63.8 per 1,000 (95% CI, 13.2–186.1), and it was significantly higher than that found in the general population in Italy (4.9 per 1,000; 95% CI, 2.8–7.8). The results of this study showed a high prevalence of CD in patients with AIH. For this reason, early serological screening testing for CD is strongly recommended for all AIH patients. J. Clin. Lab. Anal. 19:6–10, 2005. © 2005 Wiley‐Liss, Inc.

Background: The role of selected macronutrients, fatty acids and cholesterol in the etiology of prostate cancer was analyzed using data from a case-control study carried out in five Italian areas between 1991 and 2002. Patients and methods: Cases were 1294 men with incident, histologically confirmed prostate cancer, and admitted to the major teaching and general hospitals of study areas. Controls were 1451 men admitted for acute, non-neoplastic conditions to the same hospital network. Information on dietary habits was elicited using a validated food frequency questionnaire including 78 food groups and recipes. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for increasing levels of nutrient intake. Results: A direct association with prostate cancer was found for starch intake (OR = 1.4 in the highest versus the lowest quintile of intake; 95% CI: 1.1-1.8), whereas an inverse association emerged for polyunsaturated fatty acids (OR = 0.8; 95% CI: 0.6-1.0). Among polyunsaturated fatty acids, linolenic acid (OR = 0.7; 95% CI: 0.6-0.9) and linoleic acid (OR = 0.8; 95% CI: 0.6-1.0) were inversely related to prostate cancer. When the six major macronutrients were included in the same model, the adverse effect of high intake of starch and monounsaturated fatty acids was statistically significant together with the protective effect of polyunsaturated fatty acids. Results were consistent in separate strata of age, body mass index and family history of prostate cancer. Conclusions: Starch and monounsaturated fatty acids were directly associated with prostate cancer risk and polyunsaturated fatty acids were inversely associated.

Background. Primary effusion lymphoma (PEL) represents a peculiar lymphoma infected with human herpesvirus 8 (HHV-8) and occurs predominantly in human immunodeficiency virus (HIV)-infected patients. The aim of the present study was to evaluate the immunologic and virological parameters, including HHV-8 viremia, of 5 HIV-infected patients with PEL whose disease was diagnosed and treated at our institute. Methods. Five patients were enrolled in the study. Biological parameters, such as latent and lytic HHV-8 antigen levels, plasma HHV-8 load, Epstein-Barr virus plasma DNA load, HIV-1 load, and CD4 cell count, were assessed before treatment, during therapy, and at follow-up. Results. Four patients were treated with chemotherapy and highly active antiretroviral therapy (HAART), and 1 was treated with HAART alone; 3 of 5 patients reached complete remission. HHV-8 could be detected before the initiation of therapy in plasma from all patients analyzed. HHV-8 levels decreased after therapy in 4 patients. During the whole observation period, plasma HHV-8 load showed a statistically significant inverse correlation with CD4 cell count but no significant correlation with HIV load and response to therapy. Conclusions. Our analysis demonstrates that HHV-8 can be detected in the plasma at the onset of PEL; its prognostic role needs to be explored. CD4 cell count seems to be the most important indicator of progression of PEL.

We assessed the performance of a Real Time PCR assay to be used for EBV viremia evaluation in clinical specimens. Sensitivity and intra-/interassay reproducibility were evaluated by using DNA serial dilutions from the Namalwa cell line. EBV DNA was analyzed in serum samples from 39 patients (pts) with undifferentiated type nasopharyngeal carcinoma (UCNT), from 5 infectious mononucleosis (IM) pts and from 18 healthy donors. Results obtained by Real Time PCR were compared with those obtained by quantitative competitive (QC)-PCR assay.We thereafter measured the dynamics of EBV DNA load in 5 HIV-seropositive (HIV+) and 9 HIV-seronegative (HIV-, as controls) pts with lymphoma, treated with high-dose chemotherapy (HCT) followed by autologus stem-cell transplantation (ASCT). We found a sensitivity of 100% at 10 EBV copies. The Spearman correlation for both the intra- and the interassay reproducibility was statistically significant (r=0.99; p20 copies/reaction and >30% for EBV viral loads

To investigate the relation between various micronutrients and laryngeal cancer risk.A case-control study was conducted in Italy and Switzerland between 1992 and 2000. Cases were 527 patients with incident cancer of larynx, admitted to the major teaching and general hospitals of the study areas. Controls were 1297 subjects admitted for acute, non-neoplastic diseases to the same network of hospitals. Dietary habits were assessed using a validated food-frequency questionnaire. Odds ratios (OR) and their corresponding 95% confidence intervals (CI) were computed using multiple logistic regression.Significant inverse relations emerged between laryngeal cancer risk and intake of vitamin C (OR = 0.2, for the highest versus the lowest intake quintile; 95% CI: 0.2-0.4), beta-carotene (OR = 0.2; 95% CI: 0.2-0.4), alpha-carotene (OR = 0.3; 95% CI: 0.2-0.5), lutein/zeaxanthin (OR = 0.4; 95% CI: 0.3-0.6), vitamin E (OR = 0.4; 95% CI: 0.3-0.6), beta-criptoxanthin (OR = 0.4; 95% CI: 0.2-0.5), folic acid (OR = 0.4; 95% CI: 0.2-0.6), thiamin (OR = 0.4; 95% CI: 0.3-0.6), glutathione (OR = 0.5; 95% CI: 0.4-0.8), reduced glutathione (OR = 0.6; 95% CI: 0.4-0.8), vitamin B6 (OR = 0.6; 95% CI: 0.4-0.9) and potassium (OR = 0.6; 95% CI: 0.4-0.9). Direct associations were found with zinc (OR = 1.5; 95% CI: 1.0-2.2) and vitamin D (OR = 1.8; 95% CI: 1.2-2.6). Combining low intakes of vitamin C, carotene, vitamin E, and folate with heavy smoking and drinking led to ORs between 80 and 170.This study provides further support that, independently from smoking and alcohol consumption, the intake of several micronutrients, including selected antioxidants, is inversely related to laryngeal cancer risk.

Gastric cancer is one of the most frequent human tumors. Most patients are diagnosed at advanced stages, and fatal outcome is expected. Seven-hundred and seven patient charts were retrospectively reviewed. Univariate and multivariate analyses were performed to evaluate the impact of clinicopathologic and treatment variables on survival. Most patients (50%) were at advanced stages, harboring poorly differentiated tumors. Surgery, mostly palliative, was performed in 85% of patients. Chemotherapy was administered to 52% of patients. On univariate analysis, significant prognostic factors were age, TNM stage, chemotherapy, radiotherapy, tumor grade, curative surgery attempt, performance status and tumor site. On multivariate analysis, independent prognostic factors were TNM stage, tumor site, postsurgical residual disease and chemotherapy. Median survival was 16.5 months. In our study, the use of chemotherapy has been shown to be an independent factor with a favorable impact on survival, also related to the regimen used. However, phase III prospective randomized trials are awaited.

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.

The role of selected macronutrients, cholesterol, and fatty acids in the etiology of epithelial ovarian cancer was analyzed using data from a case-control study carried out in five Italian areas between January 1992 and December 1999.Cases comprised 1,031 women with incident, histologically confirmed epithelial ovarian cancer, admitted to the major teaching and general hospitals of the study areas. Controls comprised 2,411 women admitted for acute, non-neoplastic conditions to the same network of hospitals. Information on dietary habits was elicited using a validated food-frequency questionnaire including 78 food groups and recipes. Odds ratios (OR) and their corresponding 95% confidence intervals (CI) were computed by subsequent quintiles of nutrient intake.Direct associations with ovarian cancer emerged for starch intake (OR = 1.4 in the highest vs the lowest quintile of intake; 95% CI 1.1-1.8), while inverse associations emerged for monounsaturated (OR=0.7; 95% CI 0.5-0.9), and polyunsaturated (OR = 0.7; 95% CI 0.5-0.9) fatty acids. Among fatty acids, oleic (OR = 0.7; 95% CI 0.5-0.9), linoleic (OR = 0.7; 95% CI 0.5-0.9), and linolenic (OR = 0.8; 95% CI 0.6-1.0) acids were inversely related to ovarian cancer. When, however, six macronutrients were included in the same model, only the adverse effect of high starch intake remained significant. Results were consistent in separate strata of menopausal status, parity, and energy intake.Starch was directly associated, and unsaturated fatty acids were inversely associated, with ovarian cancer risk.

Endometrial carcinoma (EC) is the second most common tumor in hereditary nonpolyposis colorectal cancer (HNPCC), with an incidence rate of 60% by the age of 70 in mutation carriers. The International Collaborative Group on HNPCC revised the Amsterdam criteria and proposed a new, wider definition including extracolonic cancers. The aim of our study was to evaluate the accuracy of a new definition called Amsterdam criteria II. We updated, reclassified and compared the pedigrees of 29 women, already reported as being affected by EC and having a colorectal cancer familial background, according to the two clinical diagnostic criteria for HNPCC (Amsterdam criteria I, ACI, and Amsterdam criteria II, ACII) after two periods of observation (1990-1995 and 1995-2000). According to ACII the frequency of HNPCC in the population under study increased from 0.9% to 3.7% in the period 1990-1995 and from 3.2% to 3.7% in the period 1995-2000. ACII allowed early detection of HNPCC families and thus made it possible to provide them with a suitable surveillance program and genetic testing.

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.

We assessed separate and combined sex-specific incidence rates of oral and pharyngeal cancer for 1988-92 and oral/pharyngeal ratios from 49 different cancer registries in five continents. Incidence trends over a period of approximately 30 years were evaluated in 16 long active registries for men and four for women. Cancers of the lip, salivary glands, and nasopharynx were excluded. The incidence of both oral and pharyngeal cancer among men is highest in northern France, southern India, a few areas of central and eastern Europe, and Latin America. Among women, the highest incidence is observed in India. Oral/pharyngeal ratio is everywhere systematically lower in men compared to women. Recent trends for oral cancer are more favourable than those for pharyngeal cancer in developing countries. In developed countries, trends in oral cancer appears to be more closely correlated to changes in alcohol consumption than those of pharyngeal cancer.

Comparison of incidence and mortality data between areas is useful for monitoring the health status of a population, for exploring quality of health care, and for planning studies on determinant(s) of heterogeneous patterns. Common statistical indicators involved, together with their confidence intervals, are age-specific and cumulative rates, age-standardized rates and ratios, and expected numbers. The data required for calculations include information of event distribution according to age and residence, and corresponding population at risk. The calcula tions of these indicators, although conceptually simple, can be a cumbersome task to carry out with available statistical packages; lack of flexibility to suit the need of specific researches represents another problem. In order to facilitate descriptive epidemiological studies, we devel oped a set of Statistical Analysis System macros to compute indicators but, also, to read and write data from/to some standard file formats. Important features of these macros are their flexibility, expandibility, and ability to be transferred to various computer platforms. Moreover, macros give an added value to raw data. The method is illustrated using published incidence data from Italy.

Aims and background The aim of the study was to evaluate the impact of information level on quality of life in cancer patients previously studied for their information level. Patients and methods The information level was determined by means of a questionnaire that explored the degree of information on diagnosis and status of disease, the patient's interpretation of his/her disease status, and his/her satisfaction with the information received. Quality of life was evaluated, some months after evaluation of the information level, by means of the Functional Living Index for Cancer (FLIC) and the State-Trait Anxiety Inventory (STAI 1-2). Results A total of 175 patients were studied. Information was adequate in 53.7% of patients. An adequate level of information was present more frequently among patients aged ≤65 years and in those patients followed at a cancer institute. There was no difference in the quality of life of adequately versus inadequately informed patients. Satisfaction with the information received influenced quality of life in both age groups. Objective clinical variables (active disease present and ongoing treatment) negatively affected quality of life in patients Conclusions In the study, although the level of information did not affect the quality of life, satisfaction with the information was associated with a better quality of life. The finding stresses the importance of a sensible disclosure of diagnosis and prognosis.

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.

In order to obtain prognostic clinicopathological information, 49 cases of pure ductal carcinoma in situ of the breast (DCIS), were evaluated for the immunohistochemical expression of potential predictor markers including c-erbB-2 oncogene product, p53 protein, oestrogen (ER) and progesterone (PR) receptors, oestrogen-regulated proteins pS2 and cathepsin-D (cath-D), CD44 protein and 67-kDa laminin receptor (MLuC5). Immunohistochemical findings were compared with conventional pathological parameters, clinical findings, and the clinical outcome of the patients. When markers were matched to each other, statistical analyses provided a significant positive correlation between c-erbB-2 overexpression and p53 positivity (P < 0.01) and between ER and PR (P < 0.01), ER, PR and pS2 (P < 0.01), pS2 and MLuC5 (P < 0.05). Significant negative correlations between c-erbB-2 overexpression and ER (P < 0.05), PR (P < 0.01) and pS2 (P < 0.01) positivity was also observed. Data on the relationship between marker status and pathological findings revealed a significant positive trend between c-erbB-2, p53, and increased grade values (P < 0.05) and opposite results with SR receptor expression (P < 0.01). c-erbB-2 overexpression was further significantly associated with comedotype carcinoma (P < 0.05) and distribution of disease in confluent neoplastic ducts (P < 0.01). Although no statistically significant correlation among biological markers expression, clinical findings and outcome was demonstrated, overall this study indicates that tumour cells from a subset of DCIS, which includes comedotype carcinoma, express significantly unfavourable prognostic factors. Copyright (C) 1996 Elsevier Science Ltd

Purpose/Objectives: Patients with locally advanced esophageal carcinoma are recommended to undergo treatment with radiation and chemotherapy, which may be followed by surgery in appropriate operative candidates. Radiation has traditionally been delivered with 3D conformal radiation therapy (3D CRT). This study is evaluating early outcomes and acute and late toxicity in patients treated with Intensity Modulated Radiation Therapy (IMRT) with concurrent chemotherapy. Materials/Methods: This is a retrospective review of 17 patients with esophageal carcinoma treated with IMRT and chemotherapy from 2008 2010. Pathology includes squamous cell and adenocarcinomas. Tumor sites include middle thoracic, lower thoracic and GE junction. Initial clinical stages are TX-T3, N0-3, and M0-1. All patients received at least one cycle of concurrent 5-fluorouracil with either cisplatin or oxaliplatin. IMRT dose was 50.4 Gy in 28 fractions prescribed to a target volume which included the tumor and regional lymphatics. All IMRT plans utilized coplanar beams in a 7-9 beam arrangement. Results: Median follow-up is 9 months (range, 4-20). Median patient age is 72 (range, 55-87). Sixteen patients received 50.4 Gy via an IMRT plan, and one received 25.2 Gy. Trimodality treatment was completed in 11 patients (65%). Surgery was either esophagogastrectomy or minimally invasive esophagectomy. Of the 11 patients who proceeded to surgery, 3 (27%) had a pathologic complete response, 7 (64%) had a partial response (PR) and 1 patient (9%) had stable disease. Of the 6 patients who received chemotherapy and IMRT alone, 2 patients had a clinical PR, 1 had disease progression, and 3 did not have follow-up data available. In the initial 17 patients, there were no local or regional recurrences, though 2 patients developed distant metastases. Twelve patients are alive at last follow-up. Of the 5 deaths, 2 were due to esophageal cancer, 1 from radiation complications, 1 from chemotherapy complications, and 1 from surgical complications. Acute CTCAE V4.0 grade 3 toxicities from concurrent chemotherapy and IMRT developed in the following patients: 2 esophagitis, 1 fatigue, 1 nausea/vomiting, 4 dehydration, 1 anemia, 1 thrombocytopenia and 5 neutropenia. Patients with grade 4 toxicities included 1 thrombocytopenia and 1 neutropenia. Four patients developed late grade 3 esophageal strictures. There was one grade 4 cardiac complication, and one grade 5 pleuro-esophageal fistula. There were no cases of radiation pneumonitis or ulcers. Conclusions: IMRT is a feasible treatment modality, which may be equally efficacious to 3D CRT for the treatment of esophageal carcinoma, and may offer fewer treatment complications, including a lower incidence of pneumonitis. Author Disclosure: K.V. Kowalchik: None. G. Kim: None. E. Johnson: None. N. Paryani: None. S. Ko: None.

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.

This case-control study evaluated the relationship between bladder cancer and occupational factors in an area of North-east Italy. The study included 273 bladder cancer cases and 573 controls identified through the services of local hospitals. Information on socio-demographic characteristics, past medical history, lifestyle factors, employment in certain industries and occupational exposures was obtained by interviewing study subjects. Elevated relative risks (RR), albeit not statistically significant, were found among males ever employed in the general chemical (RR = 2.8), dye (RR = 6.9) and painting (RR = 3.1) industries. When results related to the general chemical and specialty chemical industries were combined the RR was 3.1 (95% confidence interval [CI]: 1.2-8.5). The RR increased with increasing duration and decreasing age at starting and years since quitting employment. The risk was significantly decreased for subjects ever employed in agriculture (RR = 0.6 for males, 0.5 for females), livestock farming (RR = 0.5 for males, 0.4 for females) and furniture manufacturing (RR = 0.5 for males), whereas an elevated risk was found among white collar workers (RR and 95% CI: 1.5, 1.1-2.4 and 2.7, 1.1-6.6 for males and females, respectively). These results confirm a well-known risk among subjects employed in various sectors of the chemical industry, and indicate that bladder cancer is associated with urbanization indicators. Because lifestyle factors (i.e. smoking, coffee consumption, etc.) did not totally explain the results for white collar workers, it is possible that other still undefined aspects of the urban environment play a role in bladder carcinogenesis.

In view of the persisting uncertainty concerning possible mechanisms by which high vegetable and fruit intake decreases cancer risk, foods with divergent values for potentially important micronutrients are a priority for investigation. Tomatoes are low in beta-carotene, but high in lycopene, an active antioxidative agent. In order to assess the effect of tomatoes on risk of cancers of the digestive tract, data were analyzed from an integrated series of case-control studies conducted between 1985 and 1991 in northern Italy, where tomato intake is high but, also, heterogeneous. The overall dataset included the following histologically confirmed cancer cases: oral cavity and pharynx, 314; esophagus, 85; stomach, 723; colon, 955; and rectum, 629; and a total of 2,879 controls admitted to hospital for acute non-neoplastic or non-digestive conditions, unrelated to long-term dietary modifications. Multivariate odds ratios (OR) and 95% confidence interval (CI) for subsequent quartiles of intake of raw tomatoes were derived, after allowance for age, sex, study center, education, smoking and drinking level, and tertile of total caloric intake. There was a consistent pattern of protection for all sites (OR in the upper quartile ranging between 0.4 and 0.7), most notable for gastrointestinal neoplasms. All trends in risk were highly significant. The beneficial effect of raw tomatoes in this population may be partly due to the fact that they constitute perhaps the most specific feature of the Mediterranean diet. However, if it is true that tomatoes protect against digestive-tract cancers, this is of interest from both a scientific and a public health viewpoint. (C) 1994 Wiley-Liss, Inc.

The relationship between farming and cancer risk was investigated in an integrated series of case-control studies conducted from 1985 to 1991 in the Friuli Venezia Giulia region, north-east Italy. Patients with cancer of the oral cavity and pharynx, larynx, oesophagus, colon and rectum, pancreas, breast, thyroid gland, kidney and urinary tract, bladder, prostate, soft-tissue sarcomas, Hodgkin's diseases, non-Hodgkin's lymphomas and multiple myelomas, and controls admitted to hospital for acute, non-neoplastic conditions, were interviewed. For males, a significantly elevated relative risk was seen for oral cavity and pharynx. Farming, however, was associated with a significant protection against cancer of the colon and rectum and bladder. In females, only one significant association emerged, for multiple myeloma. A few significant interactions between cancer risk and year of birth (i.e., before 1930 or 1930 and after) were observed. The risk of cancer of the larynx was significantly elevated in younger male farmers but not in older ones. Our multi-site case-control study confirms that farmers have, for some cancer sites, a distinctive pattern. Excesses of cancer of the oral cavity and pharynx in farmers are characteristic of the present study area and, possibly, of similar European rural populations who have in common high levels of alcohol consumption and, at least in the past, unbalanced diets.

A population-based case-control study of 260 patients (74 males and 186 females, mean age = 56) with cutaneous malignant melanoma and 416 controls (211 males and 205 females, mean age = 55) was conducted in Turin, north-west Italy, to examine the relation between timing of sunburns and sun exposure and melanoma risk within a southern European population, which is still relatively little investigated. Particularly elevated risk was associated with history of sunburns in childhood [odds ratio 5.9; 95% confidence interval (CI) 3.6-9.5], and such risk elevation persisted after allowance for other major melanoma risk covariates. Conversely, risk increase from history of severe sunburns lifelong was lower (odds ratio = 1.7; 95% CI: 1.1-2.4) and was eliminated by allowance for type of skin reaction to sun exposure and history of sunburns in childhood. A significant increase in the risk of cutaneous malignant melanoma was also associated with number of weeks spent on holiday at the beach not only as an adult, but also as a child.

The role of reproductive and menstrual factors and a few medical conditions linked to female hormones in the aetiology of colorectal cancer was investigated in a case-control study conducted in Pordenone province in northeastern Italy, on 89 women with colorectal cancer and 148 controls admitted to hospital for a wide spectrum of acute, non-digestive nor neoplastic disorders. After adjustment for age and social class, parous women, as compared to nulliparous ones, were significantly protected against colorectal cancer (odds ratio, OR = 0.4, [95% confidence interval, CI:0.2-0.8]) and the risk appeared to decrease with successive pregnancies up to five or more (0.2, [0.04-0.6]). Compared to women who had their first birth at age 24 or less, the OR for those who had it at 30 or older was 2.0, but the inverse trend in risk was not significant. However, among parous women only, age at first birth, but not parity, seemed to retain a certain influence. Late age at menopause seemed to decrease colorectal cancer risk (OR for menopause at age greater than or equal to 50 vs. less than 45 = 0.4, [0.2-1.0] chi 2(1) (trend) = 3.66). Conversely, age at last birth, number of abortions, years between marriage and first birth, age at menarche, pattern of menstrual cycle and occurrence of a few medical conditions potentially linked to female hormones were similarly reported by cases and controls. Due to the very limited number of oral contraceptive (OC) users (9 controls but only 1 case), and the lack of oestrogen replacement therapy users, the influence of exogenous female hormones on colorectal cancer could not be analysed meaningfully.