An important hallmark of CRC is the evasion of immune surveillance. HLA-G is a negative regulator of host's immune response. Overexpression of HLA-G protein in primary tumour CRC tissues has already ...been associated to worse prognosis; however a definition of the role of immunogenetic host background is still lacking. Germline polymorphisms in the 3'UTR region of HLA-G influence the magnitude of the protein by modulating HLA-G mRNA stability. Soluble HLA-G has been associated to 3'UTR +2960 Ins/Ins and +3035 C/T (lower levels) and +3187 G/G (high levels) genotypes. HLA-G 3'UTR SNPs have never been explored in CRC outcome. The purpose of this study was to investigate if common HLA-G 3'UTR polymorphisms have an impact on DFS and OS of 253 stage II-III CRC patients, after primary surgery and ADJ-CT based on FL. The 3'UTR was sequenced and SNPs were analyzed for their association with survival by Kaplan-Meier and multivariate Cox models; results underwent internal validation using a resampling method (bootstrap analysis). In a multivariate analysis, we estimated an association with improved DFS in Ins allele (Ins/Del +Ins/Ins) carriers (HR 0.60, 95% CI 0.38-0.93, P = 0.023) and in patients with +3035 C/T genotype (HR 0.51, 95% CI 0.26-0.99, P = 0.045). The +3187 G/G mutated carriers (G/G vs A/A+A/G) were associated to a worst prognosis in both DFS (HR 2.46, 95% CI 1.19-5.05, P = 0.015) and OS (HR 2.71, 95% CI 1.16-6.63, P = 0.022). Our study shows a prognostic and independent role of 3 HLA-G 3'UTR SNPs, +2960 14-bp INDEL, +3035 C>T, and +3187 A>G.
The cardiotoxicity of fluoropyrimidines (FP) 5-Fluorouracil and Capecitabine is often reported as acute cardiac ischemia with rest typical angina, signs of ischemia at electrocardiogram (ECG), and ...ventricular kinetics abnormalities. However, silent ischemia, effort-related toxicity, and ventricular arrhythmias (VA) have been also described. The aim of this study is to report a consecutive series of 115 patients with FP cardiotoxicity observed in a single center both within clinical prospective studies and during the clinical routine. The clinical presentation widely varied as regards symptoms, ECG abnormalities, and clinical outcomes. We report also the strategies used to prevent cardiotoxicity in a subgroup of 35 patients who continued o rechallenged FP therapy after cardiotoxicity. In nearly half of the patients, the cardiotoxicity was triggered by physical effort. Typical angina was rare: the symptoms were absent in 51% of cases and were atypical in half of the other cases. ST-segment elevation and VA were the most frequent ECG abnormality; however, ST segment depression or negative T waves were the only abnormalities in 1/3 of the cases. Troponins essays were often within the normal limits, even in presence of extensive signs of ischemia. The most effective strategy to prevent cardiotoxicity at rechallenge was reducing FP dosage and avoiding physical effort. Anti-ischemic therapies were not always effective. Raltitrexed was a safe alternative to FP. Fluoropyrimidine cardiotoxicity shows a wide variety of clinical presentations in real life, from silent ischemia to atypical symptoms, acute coronary syndrome, left ventricular dysfunction (LVD), VA, or complete atrio-ventricular block. Physical effort is the trigger of cardiotoxicity in nearly half of the cases. The recognition of cardiotoxicity cannot rely on symptoms only but requires an active screening with ECG and stress test in selected cases.
The prognosis of cutaneous melanoma (CM) differs for patients with identical clinico-pathological stage, and no molecular markers discriminating the prognosis of stage III individuals have been ...established. Genome-wide alterations in DNA methylation are a common event in cancer. This study aimed to define the prognostic value of genomic DNA methylation levels in stage III CM patients.
Overall level of genomic DNA methylation was measured using bisulfite pyrosequencing at three CpG sites (CpG1, CpG2, CpG3) of the Long Interspersed Nucleotide Element-1 (LINE-1) sequences in short-term CM cultures from 42 stage IIIC patients. The impact of LINE-1 methylation on overall survival (OS) was assessed using Cox regression and Kaplan-Meier analysis.
Hypomethylation (i.e., methylation below median) at CpG2 and CpG3 sites significantly associated with improved prognosis of CM, CpG3 showing the strongest association. Patients with hypomethylated CpG3 had increased OS (P = 0.01, log-rank = 6.39) by Kaplan-Meyer analysis. Median OS of patients with hypomethylated or hypermethylated CpG3 were 31.9 and 11.5 months, respectively. The 5 year OS for patients with hypomethylated CpG3 was 48% compared to 7% for patients with hypermethylated sequences. Among the variables examined by Cox regression analysis, LINE-1 methylation at CpG2 and CpG3 was the only predictor of OS (Hazard Ratio = 2.63, for hypermethylated CpG3; 95% Confidence Interval: 1.21-5.69; P = 0.01).
LINE-1 methylation is identified as a molecular marker of prognosis for CM patients in stage IIIC. Evaluation of LINE-1 promises to represent a key tool for driving the most appropriate clinical management of stage III CM patients.
Incidence rates of various cancers are increasing in Arab countries and are expected to reach those of industrialized ones in few decades. This paper aimed to describe the incidence rates of most ...common cancers--and/or of those cancer preventable through modifiable behaviors--recorded in the province of Setif, Algeria from 1986 through 2010.
Cancer diagnoses for the 1986-2010 period were provided by the population-based Cancer Registry of Setif, disentangled by site, morphology, age (quinquennia), sex, and calendar period. The corresponding population was obtained from the Algerian Institute of Statistics. Age-standardized rates (world population) (ASR-WR) were computed by calendar period (five quinquennias from 1986-1990 to 2006-2010), while annual percent changes (APCs) were computed for the period 1996-2010.
During the 2006-2010 period, ASR-WR for all cancer sites were 106.4/100,000 in men and 110.3 in women. The four leading cancers were: lung (18.0%); colon-rectum (9.6%); bladder (9.1%); and prostate (6.5%) in men; breast (36.4%); colon-rectum (8.5%); cervix uteri (6.0%); and thyroid (6.0%) in women. Between 1996-2010, overall cancer incidence increased statistically significantly (p < 0.05) in both men (APC = +2.5%) and women (APC = +3.7%). Statistically significant decreasing trends were observed for nasopharyngeal carcinoma (APC = -3.4%) in men, and for cervical (APC = -4.2%) and gallbladder (APC = -3.2%) cancers in women. Statistically significant increasing trends were observed for most common cancers both in men (lung:+1.8%, colon-rectum:+5.4%, prostate:+4.3%, liver:+8.9%, and bladder:+5.9%) and women (breast:+8.2%, colon-rectum:+4.5%, lung:+10.0%, liver:+5.4%, thyroid:+5.3%, and larynx:+13.8%).
International recommendations against cancer must be strongly promoted in Setif after taking into account epidemiological transition, lifestyle, and environmental changes.
tumors are a major cause of morbidity and mortality after long-term solid organ transplantation. Chronic immunosuppression strongly affects solid organ transplanted (SOT) patients' immune system by ...promoting immune evasion strategies and reactivations of viruses with oncogenic potential, ultimately leading to cancer onset. In this scenario, an oncological Surveillance Protocol integrated with biobanking of peripheral blood samples and evaluation of immunovirological and molecular parameters was activated for SOT patients at CRO-IRCCS Aviano, with the aim of identifying suitable biomarkers of cancer development.
An exploratory longitudinal study was designed based on two serial peripheral blood samples collected at least three months apart. Forty nine SOT patients were selected and stratified by tumor onset during follow-up. Spontaneous T-cell responses to EBV, CMV and tumor associated antigens, EBV-DNA and CMV-DNA loads, and circulating
mRNA levels were investigated.
Significantly higher levels of circulating
mRNA were observed 3.5-23.5 months before and close to the diagnosis of cancer as compared to tumor-free patients. Plasmatic
mRNA levels >97.73 copies/mL at baseline were significantly associated with the risk of developing
tumors (HR=4.0, 95%C.I. = 1.4-11.5, p=0.01). In particular, the risk significantly increased by 4% with every ten-unit increment in
mRNA (HR=1.04, 95%C.I. = 1.01-1.07, p=0.01).
Although obtained in an exploratory study, our data support the importance of identifying early biomarkers of tumor onset in SOT patients useful to modulate the pace of surveillance visits.
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.
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.
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).
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.
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.
ObjectivesTo 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.DesignA 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.SettingAdministrative databases from Umbria Region, Azienda Sanitaria Locale (ASL) Napoli 3 Sud (NA) and Friuli VeneziaGiulia (FVG) Region.ParticipantsWomen with breast carcinoma in situ (n=246) or invasive breast cancer (n=384) diagnosed (in primary position) between 2012 and 2014.Outcome measuresSensitivity and specificity for codes 233.0 and 174.x.ResultsFor 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.ConclusionsAdministrative 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.
Objective: To evaluate whether plasma cell-free DNA (cfDNA) was related to clinical outcome in inoperable stage I non-small cell lung cancer (NSCLC) patients undergoing stereotactic body radiotherapy ...(SBRT).
Materials and methods: Plasma cfDNA was assessed at baseline, before the last day and 45 days after the end of SBRT, in 22 NSCLC patients. Twenty-two healthy controls were also evaluated.
Results: Plasma cfDNA was higher in patients than in controls. An association with unfavourable disease-free survival was found for continuous baseline cfDNA increments (HR = 5.9, 95%CI: 1.7-19.8, p = 0.04).
Conclusion: Plasma cfDNA may be a promising prognostic biomarker in high-risk NSCLC patients.
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.
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