[Show abstract][Hide abstract] ABSTRACT: An increase in the incidence of breast cancer in women aged<40 years has been reported in recent years. Increased incidence could be partly explained by subtle detection biases, but the role of other risk factors cannot be ruled out. The purpose of the present study was to investigate the changes in temporal trends in breast cancer incidence in European women aged 20-39 years at diagnosis. Age specific breast cancer incidence rates for 17 European Cancer Registries were retrieved for the calendar period 1995-2006. Cancer registries data were pooled to reduce annual fluctuations present in single registries and increase incidence rates stability. Regression models were fitted to the data assuming that the number of cancer cases followed the Poisson distribution. Mean annual changes in the incidence rate (AIC) across the considered time window were calculated. The AIC estimated from all European registries was 1.032 (95% CI=1.019-1.045) and 1.014 (95% CI=1.010-1.018) in women aged 20-29 and 30-39 years old at diagnosis, respectively. The major change was detected among women aged 25-29 years at diagnosis: AIC=1.033 (95% CI=1.020-1.046). The upward trend was not affected when registries with high or low AIC were removed from the analysis (sensitivity analysis). Our findings support the presence of an increase in the incidence of breast cancer in European women in their 20s and 30s during the decade 1995-2006. The interpretation of the observed increase is not straightforward since a number of factors may have affected our results. The estimated annual increase in breast cancer incidence may result in a burden of the disease that is important in terms of public health and deserves further investigation of possible risk factors.
Breast Cancer Research and Treatment 03/2012; 134(1):363-70. · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Development of graphical/visual presentations of cancer etiology caused by environmental stressors is a process that requires combining the complex biological interactions between xenobiotics in living and occupational environment with genes (gene-environment interaction) and genomic and non-genomic based disease specific mechanisms in living organisms. Traditionally, presentation of causal relationships includes the statistical association between exposure to one xenobiotic and the disease corrected for the effect of potential confounders.
Within the FP6 project HENVINET, we aimed at considering together all known agents and mechanisms involved in development of selected cancer types. Selection of cancer types for causal diagrams was based on the corpus of available data and reported relative risk (RR). In constructing causal diagrams the complexity of the interactions between xenobiotics was considered a priority in the interpretation of cancer risk. Additionally, gene-environment interactions were incorporated such as polymorphisms in genes for repair and for phase I and II enzymes involved in metabolism of xenobiotics and their elimination. Information on possible age or gender susceptibility is also included. Diagrams are user friendly thanks to multistep access to information packages and the possibility of referring to related literature and a glossary of terms. Diagrams cover both chemical and physical agents (ionizing and non-ionizing radiation) and provide basic information on the strength of the association between type of exposure and cancer risk reported by human studies and supported by mechanistic studies. Causal diagrams developed within HENVINET project represent a valuable source of information for professionals working in the field of environmental health and epidemiology, and as educational material for students.
Cancer risk results from a complex interaction of environmental exposures with inherited gene polymorphisms, genetic burden collected during development and non genomic capacity of response to environmental insults. In order to adopt effective preventive measures and the associated regulatory actions, a comprehensive investigation of cancer etiology is crucial. Variations and fluctuations of cancer incidence in human populations do not necessarily reflect environmental pollution policies or population distribution of polymorphisms of genes known to be associated with increased cancer risk. Tools which may be used in such a comprehensive research, including molecular biology applied to field studies, require a methodological shift from the reductionism that has been used until recently as a basic axiom in interpretation of data. The complexity of the interactions between cells, genes and the environment, i.e. the resonance of the living matter with the environment, can be synthesized by systems biology. Within the HENVINET project such philosophy was followed in order to develop interactive causal diagrams for the investigation of cancers with possible etiology in environmental exposure.
Causal diagrams represent integrated knowledge and seed tool for their future development and development of similar diagrams for other environmentally related diseases such as asthma or sterility. In this paper development and application of causal diagrams for cancer are presented and discussed.
Environmental Health 01/2012; 11 Suppl 1:S9. · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An important issue in human biomonitoring is determining how exposure duration affects the kinetics of molecular biomarkers. In this study we compare the influence of exposure variables on DNA adducts.
DNA adducts were analysed by 32P-postlabelling in lympho/monocytes of 677 Caucasian subjects.
After correction for other variables, DNA adducts increased depending on the length of occupational and smoke exposures. Higher DNA adducts were detected in workers with more than 14 years of exposure than in workers with shorter exposures (RR = 1.19, p = 0.049) and in smokers with more than 10 years of exposure than in smokers with shorter exposure (RR = 1.21, p <0.001).
Exposure length is the primary factor affecting DNA-adduct level in lympho/monocytes both in smokers and in occupationally exposed subjects.
[Show abstract][Hide abstract] ABSTRACT: Identification of modifiable risk factors is an attractive approach to primary prevention of esophageal adenocarcinoma (EAC) and esophagogastric junction adenocarcinoma (EGJAC). We conducted a review of the literature to investigate the association between specific dietary components and the risk of Barrett’s esophagus (BE), EAC and EGJAC, supposing diet might be a risk factor for these tumors. Consumption of meat and high-fat meals has been found positively associated with EAC and EGJAC. An inverse association with increased intake of fruit, vegetables and antioxidants has been reported but this association was not consistent across all studies reviewed. Few studies have examined the association between diet and BE. Additional research is needed to confirm the aforementioned association and clarify the mechanisms by which dietary components affect the risk of developing EAC and EGJAC. Future studies could advance our knowledge by emphasizing prospective designs to reduce recall bias, by using validated dietary intake questionnaires and biological measures and by considering important confounders such as gastro-esophageal reflux disease (GERD) symptoms, tobacco and alcohol use, biometrics, physical activity, and socioeconomic factors.
Gastroentérologie Clinique et Biologique 10/2010; 35(1):7-16. · 0.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Self-expanding metal stents (SEMS) are used to treat obstructive malignancies of the esophagus or esophagogastric junction; however, a potential complication is recurrent dysphagia because of tissue in/overgrowth. The placement of a second SEMS is one strategy to re-establish patency of the esophageal lumen. We evaluated the safety and efficacy of an alternative and likely less costly approach: placing a self-expanding plastic stent (SEPS) to manage relapsing dysphagia in patients previously treated with a partially covered SEMS. From December 2007 to January 2009, 13 patients previously treated with a SEMS for malignant dysphagia underwent treatment by inserting a SEPS to palliate relapsing dysphagia, as a result of tissue in/overgrowth. Stenosis was located in the upper esophagus in one patient, in the middle in four patients, and in the lower esophagus in eight patients. Clinical evaluation was performed at the time of stent placement, after 1 week, and then, monthly until death. The SEPS was successfully placed in a single treatment session for all patients. No preliminary dilation was required, and no further treatment was necessary for any patient. Before stenting, the median dysphagia score was 4 (range 3-4), and 1 week later the score was 0 for all patients. The resolution of dysphagia persisted until patient death (from tumor progression). The mean survival after the SEPS insertion was 4 months (range 3-8). This case series supports the use of a SEPS to palliate dysphagia from tissue in/overgrowth of a SEMS. Future clinical trials with larger patient samples are warranted.
Diseases of the Esophagus 09/2010; 23(7):590-6. · 1.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Standard endoscopic mucosal resection (EMR) is limited with regard to lesions below or involving the ileocecal valve. We describe the treatment and outcomes when using cap-assisted EMR (EMR-C) to remove large laterally spreading tumors (LSTs) with ileal infiltration in seven patients (median age 74 years). Each LST (median size 40 mm) was successfully resected in one session (median procedure time 50 minutes). Intraprocedural and early bleeding occurred in two patients, and delayed hemorrhage in one. Circumferential resection of the ileum caused asymptomatic strictures in six patients, with regression during follow-up for five. We conclude that the novel EMR-C method is a potentially effective treatment for cecal LST involving the distal ileum. Serious complications such as perforation or symptomatic strictures of the ileocecal valve were not observed and any procedure-related bleeding was easily controlled.
[Show abstract][Hide abstract] ABSTRACT: Asbestos is the principal etiological factor of malignant mesothelioma (MM), accounting for more than 80% of all tumor cases. However, other co-factors, including genetic susceptibility may play a role in the etiology of this disease, possibly modulating the effects of exposure to asbestos and other carcinogenic mineral fibers. The frequent report of familial clustering was the first indication supporting the involvement of genetic factors. Therefore, we performed an extensive literature search to evaluate existing studies reporting familial cases of MM.
Published reports addressing the issue of familial susceptibility to MM have been searched through PubMed using keywords and free text tools. Eighty-two citations were retrieved and 20 of them actually reported a familial cluster of MM. Three more articles were identified through the references. The probability that the observed familial clusters of mesothelioma could have randomly occurred in exposed families was evaluated with the Family History Score Zi (FHSi).
The result of this analysis suggested that clustering of MM cases in families exposed to asbestos may be explained with the additional contribution of other familial factors. The FHSi allowed to reject the hypothesis of random occurrence of these clusters with a probability of a first type error ranging between 1 per cent and 1 per billion.
The evaluation of the published materials supports the hypothesis that - although familial clustering of MM is largely attributable to shared asbestos exposure - the additional contribution of factors dealing with genetic susceptibility may play a role in the etiology of MM.
Mutation Research/Reviews in Mutation Research 03/2008; 658(3):162-71. · 6.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The predictive and prognostic role of neuron-specific enolase (NSE) in non-small cell lung cancer (NSCLC) is still under debate.
To study these aspects, serum NSE was prospectively measured at baseline of first-line chemotherapy treatment and tested for correlation with clinical outcome in 129 advanced NSCLC patients.
An objective response was achieved in 27 out of 65 (41.5%) patients with NSE < 8.6 ng/ml and in 38 out of 64 (59.4%) patients with NSE > or = 8.6 ng/ml (p = 0.05). Logistic analysis confirmed the positive association between objective response and NSE values > or = 8.6 ng/ml (odds ratio = 1.69; 95% confidence interval: 1.09-2.63; p = 0.02). Overall median survival was 10.8 months. A statistically significant prognostic effect on survival was found for performance status, stage and response to treatment, but not for baseline NSE value.
Based on these data, baseline circulating tumor NSE levels appear to have a weak predictive role, but not a prognostic significance in patients with advanced NSCLC submitted to standard chemotherapy.
Anticancer research 01/2008; 28(1B):507-13. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Self-expanding metal stents (SEMS) have gained a wide consensus in the treatment of malignant dysphagia. The small diameter of the delivery system has reduced the morbidity related to their placement. These stents could be a reasonable option also in patients with benign refractory esophageal strictures. Two types of stents have been used: self-expandable plastic stent (SEPS; Polyflex®) and SEMS. Fluoroscopy is recommended, and predeployment dilation should be performed when a SEPS is placed. SEMS should be completely covered with a silicone layer that opposes the granulomatous ingrowth through the meshes, which prevents imbedding and allows easy retrieval. Migration represents the most frequent complication and is due to the lack of imbedding of these stents. The techniques of stent placement are similar to those when stents are placed for malignant disease. Dilation is not advisable before placing a SEMS, but may be performed after its release. The prolonged and stable dilation of the endoprosthesis is believed to work in some patients by prevention of the scarring process and avoiding the adhesion of damaged areas (such as after extensive endoscopic mucosal resection). Remodeling of scar tissue by the indwelling stent is believed to occur in chronic strictures but is difficult to obtain in patients with refractory hypopharyngeal strictures following radiation therapy. Stents need to be removed, the timing of which is variable but usually more than 4 to 8 weeks after placement. Prolonged placement may lead to complications such as reactive overgrowth and result in a new stricture. This review analyses the risk and benefits of self-expandable stents in the management of dysphagia for benign esophageal strictures.
Techniques in Gastrointestinal Endoscopy 01/2008; 10(4):164-174.
[Show abstract][Hide abstract] ABSTRACT: Self-expanding metal stents (SEMS) provide effective palliation in patients with malignant dysphagia, although severe complications and mortality may result. We performed a prospective controlled trial to compare a new self-expanding polyester mesh stent (Polyflex) with SEMS (Ultraflex).
One hundred one patients with unresectable esophageal carcinoma were randomized to placement of a Polyflex (N=47) or a partially covered Ultraflex (N=54) stent. Patients with esophagogastric junction (EGJ) malignancy were excluded.
Placement was successful in 46 (98%) patients with the Polyflex and 54 (100%) patients with the Ultraflex stent. In one patient, the Polyflex stent could not be placed. After 1 wk, dysphagia was improved by at least 1 grade in 100% of the Polyflex group and in 94% of the Ultraflex group. Major complications were observed in 48% of the Polyflex group and 33% of the Ultraflex group. Intraprocedural perforation occurred in 1 Polyflex and 1 Ultraflex patient. Two Polyflex patients had postprocedural hemorrhage. Twenty (44%) patients with a Polyflex stent and 18 (33%) with an Ultraflex stent had recurrent dysphagia because of tumor overgrowth, stent migration, hyperplastic granulomatous reaction, or food bolus impaction. Multivariate analysis showed a significantly higher complication rate with Polyflex than with Ultraflex stents (odds ratio 2.3, 95% CI 1.2-4.4). However, median survival was 134 days with Polyflex and 122 days with Ultraflex stents (P=NS).
No difference was seen in palliation of dysphagia between the two stents. Significantly more complications, especially late stent migration, were observed in the Polyflex group.
The American Journal of Gastroenterology 01/2008; 102(12):2667-77. · 9.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: High levels of serum-soluble mesothelin family proteins (SMRP) have been found to be associated with malignant mesothelioma (MM), but not lung cancer (LC). To verify the clinical role of this marker for both these tumors, we tested serum SMRP in the largest population of thoracic cancers ever assembled.
SMRP blood concentrations were measured in 107 patients with MM, 215 patients with LC, 130 patients with benign respiratory diseases (BRD), and 262 controls. Statistical comparison between mean serum SMRP levels in all groups was done and receiver operating characteristic curves were constructed to evaluate the performance of this marker.
SMRP levels were significantly higher in patients with MM and LC than in patients with benign respiratory diseases and controls (P < 0.001). The area under the receiver operating characteristic curve for serum SMRP discriminating MM and controls was 0.77 (95% confidence interval, 0.71-0.83), with a best cutoff of 1.00 nmol/L (sensitivity, 68.2%; specificity, 80.5%). In both MM and LC, serum SMRP levels did not differ significantly between early and late stages. High SMRP levels proved to be an independent negative prognostic factor in patients with MM.
Our data confirm that serum SMRP is a promising marker for the diagnosis, prognosis, and clinical monitoring of MM. We found that serum SMRP dosage may prove helpful in LC diagnosis as well. These data may also have positive repercussions on secondary preventive medical strategies for workers previously exposed to asbestos.
Clinical Cancer Research 09/2007; 13(17):5076-81. · 7.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Adenomas of the duodenum have been described in patients with familial adenomatous polyposis (FAP). Patients with FAP are at high risk for the development of periampullary cancer. The aim of our study was to evaluate if endoscopic visualization of small polyps, often overlooked at standard endoscopic examination, was improved by chromoendoscopy. Ten patients with FAP and previous colectomy underwent upper gastrointestinal endoscopy. Two skilled endoscopists were involved for each endoscopy. Evaluation of number and diameter of polyps was made before and after staining. After staining we detected a larger number of duodenal polyps than found at the standard endoscopic examination, the difference being statistically significant. This result seems to suggest that chromoendoscopy may improve diagnostic yield of endoscopy. Further studies are needed to suggest the best surveillance program and the appropriate therapeutic modality for these patients.
Digestive Diseases and Sciences 09/2007; 52(8):1906-9. · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Individual response to oxidative stress, due to exposure to asbestos fibres plays a significant role in the malignant pleural mesothelioma (MPM) etiology. The differential impact on MPM risk of polymorphic alleles of glutathione-S-transferases (GSTs) and manganese superoxide dismutase (MnSOD/SOD2) genes involved in the defence against oxidative damage has been investigated. Ninety cases of MPM and 395 controls were genotyped using the arrayed-primer extension technique. Logistic regression analysis was applied to assess the predictive role of single nucleotide polymorphisms (SNPs) potentially involved in MPM carcinogenesis after adjustment for potential confounders. An increased risk of MPM was found in subjects bearing a GSTM1 null allele (OR = 1.69, 95% CI = 1.04-2.74; p = 0.034), and in those with the Ala/Ala genotypes at codon 16 within MnSOD (OR = 3.07, 95% CI = 1.55-6.05; p = 0.001). A stronger effect of MnSOD was observed among patients without a clear exposure to asbestos fibres. No effect was found for GSTA2, GSTA4, GSTM3, GSTP1 and GSTT1 genes. These findings, if replicated, contribute substantial evidence to the hypothesis that oxidative stress and cellular antireactive oxygen species systems are involved in the pathogenesis and in the natural history of MPM.
International Journal of Cancer 07/2007; 120(12):2739-43. · 6.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The management of patients with refractory hypopharyngeal strictures after surgery in combination with radiation therapy is disappointing, and nutrition through feeding tubes is often required.
To evaluate the efficacy and safety of a modified self-expanding Niti-S metal stent in the treatment of hypopharyngeal strictures after combined therapy for laryngeal cancer.
A general hospital and a university hospital.
Seven consecutive patients were included. One of them did not have laryngectomy.
All patients received a modified Niti-S stent.
Improvement of dysphagia, avoiding periodic bougienage, and enteral nutrition through feeding tubes.
After placement of the first stent, dysphagia improved in all patients. Six of 7 patients developed stent migration and/or granulomatous tissue ingrowth or overgrowth. Additional stents were placed in all patients after a median of 3 months after the previous stent placement. One patient developed an esophagorespiratory fistula caused by a Polyflex stent. Two patients died of causes unrelated to the stent. The remaining 5 patients remained alive and asymptomatic after a median follow-up of 10 months.
Periodic stent exchange. Stent placement did not resolve the stricture definitively. We had a limited number of patients and have no long-term outcome data yet.
The use of this modified Niti-S stent avoids both enteral nutrition through feeding tubes and the need for periodic bougienage in patients with difficult-to-treat benign hypopharyngeal strictures.
[Show abstract][Hide abstract] ABSTRACT: Dysphagia is the most distressing symptom in patients with cancer-related oesophageal obstruction. Endoscopic palliation aims to restore swallowing, avoid reintervention and to reduce hospitalization. This study reports an experience with a new self-expandable plastic stent (Polyflex) in patients with unresectable oesophageal and oesophagogastric junction cancer.
Sixty patients were prospectively collected. The cause of obstruction was oesophageal squamous cell carcinoma (44) and adenocarcinoma (eight), lung cancer (seven) and thyroid tumour (one).
The stent was successfully placed in 59 patients. Early minor complications occurred in 19 patients (32%), and major complications in 13 (22%). Death occurred in three patients owing to pulmonary embolism (one) and massive haemorrhage (two). Recurrent dysphagia for early stent migration was observed in seven patients. Delayed stent migration occurred in five patients and tumour overgrowth in eight patients. The mean dysphagia score of 2.8 improved to a mean score of 1.0 after stenting (P<0.001). Overall median survival time was 4.6 months.
Our study suggests that Polyflex stents are competitive with metal stents, with similar efficacy but lower cost. Technical improvements, however, are required to make these stents more user friendly. Large randomized clinical studies are needed to guide in the choice among the different available stents.
European Journal of Gastroenterology & Hepatology 04/2007; 19(3):195-203. · 1.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pleural Malignant Mesothelioma (MM) is a highly aggressive neoplasm with a poor survival rate, hard diagnosis and treatment. The incidence of MM in Western Europe countries is expected to increase drammatically in the next 10-15 years. In spite of this drammatic scenario, at this time the only instruments for screening and early diagnosis are based on radiological tests with evident ethical and economical problems. For this reason, some authors are evaluating biological indicators with the significance of screening and early diagnosis markers. One of the most promising marker is serum mesothelin (SMRP). SMRP levels appeares to be significantly related to MM and its clinical (diagnostic/prognostic) usefulnes has been suggested. The purpose of this research is to show SMRP trend in relation both to the course of the disease and the response to therapies in some Epithelioid MM patients. The analysis of SMRP levels in these patients suggests that it may be a useful marker for monitoring the response to treatment. In fact, it was observed that SMRP increases in patients who did not respond to therapy, it tends to remain stable when therapies results into a clinical stabilization, while it decreases after surgical procedure and in case of clinical improvement.
Giornale italiano di medicina del lavoro ed ergonomia 01/2007; 29(3 Suppl):339-42.
[Show abstract][Hide abstract] ABSTRACT: High dosages of Serum Mesothelin have been demonstrated to be significantly associated to Pleural Malignant Mesothelioma. We recently demonstrated that Serum Mesothelin may be clinically helpful both for diagnostic and prognostic purposes, with the best cut-off corresponding to 1 nM. We also discovered that high levels of Serum Mesothelin are significantly associated to Lung Cancer. The usefulness of this marker in secondary prevention has been suggested, though never demonstrated. We therefore started a long-term prospective cohort study including previously asbestos-exposed workers. These subjects periodically underwent both radiological tests and serum mesothelin dosages. As a mid-term goal of this longitudinal study we decided to check the variability of mesothelin dosages, comparing baseline and follow-up values, as well as the possible correlation with age, duration of exposure, smoking, any abnormality of respiratory functional tests (RFT) and/or radiological tests. At baseline, Mesothelin mean value was 0.66 +/- 0.4 (range 0.08-2.2 nM). Both age (p = 0.04) and abnormal thoracic TC (p = 0.04) were significantly correlated with increased serum mesothelin levels and increasing age. No association was found between baseline mesothelin levels and duration of asbestos exposure (p = 0.5), smoking habits (p = 0.2), abnormal RFT, DLCO (carbon monoxide diffusing capacity) or thoracic X-ray. No significant variation was observed between mesothelin values at baseline and at follow-up (p = 0.2).
Giornale italiano di medicina del lavoro ed ergonomia 01/2007; 29(3 Suppl):342-5.