Cancer risk and the complexity of the interactions between environmental and host factors: HENVINET interactive diagrams as simple tools for exploring and understanding the scientific evidence.

BACKGROUND: 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. METHODS: 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. INTRODUCTION: 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. RESULTS: 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.

Duration of exposure to environmental carcinogens affects DNA-adduct level in human lymphocytes.

BACKGROUND AND OBJECTIVE: 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. METHODS: DNA adducts were analysed by 32P-postlabelling in lympho/monocytes of 677 Caucasian subjects. RESULTS: 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). CONCLUSIONS: Exposure length is the primary factor affecting DNA-adduct level in lympho/monocytes both in smokers and in occupationally exposed subjects.

Predictive and prognostic significance of neuron-specific enolase (NSE) in non-small cell lung cancer.

BACKGROUND: The predictive and prognostic role of neuron-specific enolase (NSE) in non-small cell lung cancer (NSCLC) is still under debate. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Clinical significance of serum mesothelin in patients with mesothelioma and lung cancer.

PURPOSE: 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. EXPERIMENTAL DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.

Genetic susceptibility to malignant mesothelioma and exposure to asbestos: the influence of the familial factor.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Functional analysis of c-Met/hepatocyte growth factor pathway in malignant pleural mesothelioma.

c-Met receptor tyrosine kinase (RTK) has not been extensively studied in malignant pleural mesothelioma (MPM). In this study, c-Met was overexpressed and activated in most of the mesothelioma cell lines tested. Expression in MPM tissues by immunohistochemistry was increased (82%) in MPM in general compared with normal. c-Met was internalized with its ligand hepatocyte growth factor (HGF) in H28 MPM cells, with robust expression of c-Met. Serum circulating HGF was twice as high in mesothelioma patients as in healthy controls. There was a differential growth response and activation of AKT and extracellular signal-regulated kinase 1/2 in response to HGF for the various cell lines. Dose-dependent inhibition (IC50 < 2.5 micromol/L) of cell growth in mesothelioma cell lines, but not in H2052, H2452, and nonmalignant MeT-5A (IC50 > 10 micromol/L), was observed with the small-molecule c-Met inhibitor SU11274. Furthermore, migration of H28 cells was blocked with both SU11274 and c-Met small interfering RNA. Abrogation of HGF-induced c-Met and downstream signaling was seen in mesothelioma cells. Of the 43 MPM tissues and 7 cell lines, we have identified mutations within the semaphorin domain (N375S, M431V, and N454I), the juxtamembrane domain (T1010I and G1085X), and an alternative spliced product with deletion of the exon 10 of c-Met in some of the samples. Interestingly, we observed that the cell lines H513 and H2596 harboring the T1010I mutation exhibited the most dramatic reduction of cell growth with SU11274 when compared with wild-type H28 and nonmalignant MeT-5A cells. Ultimately, c-Met would be an important target for therapy against MPM.

Polyflex stents for malignant oesophageal and oesophagogastric stricture: a prospective, multicentric study.

OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

SV40 enhances the risk of malignant mesothelioma among people exposed to asbestos: a molecular epidemiologic case-control study.

We conducted a case-control study on asbestos exposure and presence of SV40 in tumor samples of malignant mesotheliomas (MMs) and bladder urotheliomas (BUs). PCR analysis revealed the presence of SV40 DNA (SV40+) in eight (42.1%) MMs and 6 (33.3%) BUs. The odds ratio for MM Asb- and SV40+ was 0.4 [95% confidence interval (95% CI), 0.03-4.0], for Asb+ and SV40- was 3.6 (95% CI, 0.6-21.0), and for Asb+ and SV40+ was 12.6 (95% CI, 1.2-133.9). Our results suggest that SV40 increases the risk of MM among individuals exposed to asbestos.

Trends in incidence rates of oesophagus and gastric cancer in Italy by subsite and histology, 1986-1997.

OBJECTIVE: Population-based studies in Western countries suggest that the incidence of oesophageal adenocarcinoma (OA) and gastric cardia adenocarcinoma (GCA) is increasing, whereas the incidence of distal gastric carcinoma and oesophageal squamous cell carcinoma (OSCC) is declining. This is the first population-based study carried out in a southern European region to evaluate the time trends in incidence rates of oesophageal and gastric tumours according to subsite and histology over the period 1986-1997. METHODS: Cancer cases were drawn from seven registries of the Italian Network of Cancer Registries, which covers approximately 9% of the Italian population (annual average 5 027 944). Time trends in age and sex-standardized incidence rates were reported. Estimated annual percentage changes (EAPC) and related 95% confidence intervals (CI) were estimated by modelling age, sex, subsite and morphology-specific incidence rates through Poisson log-linear regression, and whenever necessary negative-binomial regression. Overall, 25 895 gastric and 2497 oesophageal carcinomas were examined. RESULTS: On the whole, an increasing trend was observed for OA plus GCA. The increase was statistically significant in younger women (<60 years: EAPC 3.7; 95% CI 0.2; 7.3) and in older men (>75 years: EAPC 4.0; 95% CI 1.2; 6.9). Similar trends were also observed in proximal gastric cancer (GCA plus fundus). A decline in the stomach subfundus incidence was observed in both sexes and in each age group. OSCC decreased significantly in men (EAPC-2.6; 95% CI-4.1;-0.9). CONCLUSIONS: It is plausible that the different tendencies in oesophageal and proximal gastric cancer in men and women are attributable to heterogeneous distributions of risk factors by sex or age.

Endoscopic mucosal resection of large hyperplastic polyps in 3 patients with Barrett's esophagus.

AIM: To report the endoscopic treatment of large hyperplastic polyps of the esophagus and esophago-gastric junction (EGJ) associated with Barrett's esophagus (BE) with low-grade dysplasia (LGD), by endoscopic mucosal resection (EMR). METHODS: Cap fitted EMR (EMR-C) was performed in 3 patients with hyperplastic-inflammatory polyps (HIPs) and BE. RESULTS: The polyps were successfully removed in the 3 patients. In two patients, with short segment BE (SSBE) (<= 3 cm), the metaplastic tissue was completely excised. A 2 cm circumferential EMR was performed in one patient with a polyp involving the whole EGJ. A simultaneous EMR-C of a BE-associated polypoid dysplastic lesion measuring 1 cm multiply 10 cm, was also carried out. In the two patients, histologic assessment detected LGD in BE. No complications occurred. Complete neosquamous re-epithelialization occurred in the two patients with SSBE. An esophageal recurrence occurred in the remaining one and was successfully retreated by EMR. CONCLUSION: EMR-C appears to be a safe and effective method for treating benign esophageal mucosal lesions, allowing also the complete removal of SSBE.

Metabolic genotypes as modulators of asbestos-related pleural malignant mesothelioma risk: a comparison of Finnish and Italian populations.

The role of CYP1A1, GSTM1, GSTT1, EPHX1, and NAT2 genotypes in susceptibility to malignant mesothelioma (MM) was compared in two case-control studies, previously conducted in two countries where different types of asbestos fibers have been used [Hirvonen et al., 1995. Inherited GSTM1 and NAT2 defects as concurrent risk modifiers in asbestos-related human malignant mesothelioma. Cancer Res. 55, 2981-2983; Hirvonen et al., 1996. Glutathione S-Transferase and N-Acetyltransferase genotypes and asbestos-associated pulmonary disorders. J. Natl. Cancer Inst.88, 1853-1856; Neri et al., 2005. Pleural malignant mesothelioma, genetic susceptibility and asbestos exposure. Mutat. Res. 592, 36-44]. Fifty-seven asbestos-exposed MM patients and 255 controls were recruited in Italy, 48 cases and 121 controls in Finland. In order to make the two studies comparable, they have been updated and new genotyping analyses have been performed. The NAT2 fast acetylator and EPHX1 low-activity genotypes were positively associated with MM in the Italian study, while they were negatively associated with this malignancy in the Finnish one. A combined significant effect was also observed in the Italian study for the NAT2 fast acetylator and EPHX1 low-activity genotypes, while this combination was protective in the Finnish study. Combination of NAT2 fast acetylator and GSTM1 null genotype posed a significantly increased risk of MM in the Italian, but not in the Finnish study. The opposite results obtained in Finland and Italy may be ascribed to random chance, but a role may be hypothesized for the fact that different types of asbestos have been used in the two countries.

High frequency of micronuclei in peripheral blood lymphocytes as index of susceptibility to pleural malignant mesothelioma.

We evaluated the frequency of micronuclei (MN) in peripheral blood lymphocytes of patients with pleural malignant mesotelioma (MM), lung cancer, benign respiratory diseases, and healthy controls. A significant increased frequency of MN was observed in patients with MM in comparison with all the other groups (median, 11.4 binucleated MN/1000 binucleated cells versus 5.1, 6.1, and 6.2, respectively). No association was found between MN and asbestos exposure. Recently, genetic susceptibility associated with asbestos exposure has been recognized in the development of MM. The presence of high frequency of MN in peripheral blood lymphocytes of patients with MM could represent a useful index of individual susceptibility to this tumor.

Endoscopic mucosal resection for high-grade dysplasia and intramucosal carcinoma in Barrett's esophagus: an Italian experience.

AIM: To evaluate endoscopic mucosal resection (EMR) in patients with high-grade dysplasia (HGD) and/or intramucosal cancer (IMC) in Barrett's esophagus (BE). METHODS: Between June 2000 and December 2003, 39 consecutive patients with HGD (35) and/or IMC (4) underwent EMR. BE >30 mm was present in 27 patients. In three patients with short segment BE (25.0%), HGD was detected in a normal appearing BE. Lesions had a mean diameter of 14.8+/-10.3 mm. Mucosal resection was carried out using the cap method. RESULTS: The average size of resections was 19.7+/-9.4 x 14.6+/-8.2 mm. Histopathologic assessment post-resection revealed 5 low-grade dysplasia (LGD) (12.8%), 27 HGD (69.2%), 2 IMC (5.1%), and 5 SMC (-12.8%). EMR changed the pre-treatment diagnosis in 10 patients (25.6%). Three patients with SMC underwent surgery. Histology of the surgical specimen revealed 1 T0N0 and 2 T1N0 lesions. The remaining two patients were cancer free at 32.5 and 45.6 mo, respectively. A metachronous lesion was detected after 25 mo in one patient with HGD. Intra-procedural bleeding, controlled at endoscopy, occurred in four patients (10.3%). After a median follow-up of 34.9 mo, all patients remained in remission. CONCLUSION: In the medium term, EMR is effective and safe to treat HGD and/or IMC within BE and is a valuable staging method. It could become an alternative to surgery.

Pleural malignant mesothelioma, genetic susceptibility and asbestos exposure.

Pleural malignant mesothelioma (MM) is a rare but extremely aggressive cancer. The limited impact of standard therapeutic treatments on survival rates makes the identification of factors that increase the individual risk a leading priority. The high proportion of cases explained by exposure to asbestos has guided intervention policies to an effective ban of this compound from our environment. However, MM cannot be solely attributed to this agent, and the role of predisposing factors and their interaction with asbestos exposure is increasingly studied. The role of mEH, GSTM1, GSTT1, NAT2, and CYP1A1 genotypes in modulating susceptibility to MM was examined in a case-control study of 80 subjects with a confirmed diagnosis of MM and 255 controls. Subjects with low mEH activity showed a significantly increased risk of MM (OR, 2.51; 95% CI, 1.11-5.68). The association was stronger in the group with low asbestos exposure (OR, 7.83; 95% CI, 0.98-62.60). A significant increased risk of MM was also found in NAT2 fast acetylators (OR, 1.74; 95% CI, 1.02-2.96). The presence of synergisms between genotypes, i.e., mEH and NAT2 (LRT for heterogeneity p<0.023), mEH and GSTM1 (LRT p<0.061), and NAT2 and GSTM1 (LRT p<0.049), combined with the interaction observed with exposure to asbestos, suggests the presence of gene-environment and gene-gene interactions in the development of MM, although the size of the study group does not allow to draw clearcut conclusions. Since genetic polymorphisms can also modify the extent of genetic damage occurring in subjects exposed to carcinogens, we measured the frequency of micronuclei in peripheral blood lymphocytes of a subgroup of MM cases. The limited number of cases (28) did not allow to observe significant effects. In conclusion, these results strengthen the hypothesis that individual susceptibility to MM can be modulated by the interaction between polymorphic genes involved in the metabolism and the intensity of asbestos exposure.

Barrett's esophagus: an update.

Barrett's esophagus (BE) is a complication observed in a small subset of patients with chronic gastroesophageal reflux. It is characterized by the presence of intestinal-type goblet cells in biopsies from the lower esophagus. The prevalence of BE increases with age, affecting 1% of the population older than 60 years. A genetic predisposition to reflux disease has been proposed. In a twin study of reflux disease, concordance was greater in monozygotic than dizygotic twins. An association between BE and esophageal adenocarcinoma, the incidence of which has increased remarkably in the last few decades, has been established. Esophagogastric junction cancers can arise from small areas of cardia intestinal metaplasia (CIM). Regular endoscopic and histologic follow-up of BE patients is recommended. Surveillance of patients with CIM is not advised. Chromoendoscopy may help to detect areas of high-grade dysplasia (HGD). The ablation of BE, e.g. by PDT or argon plasma coagulation, is not yet proven to reduce the cancer risk. Esophagectomy is still the standard management of HGD. Endoscopic mucosal resection may be used for visible, localized lesions with HGD, and this technique may be combined with thermal ablation for areas of HGD without visible abnormality.

Simian virus 40 and malignant mesothelioma (Review).

Simian virus 40 (SV40) was recognized as a contaminant of early poliovirus vaccines that were provided to millions of individuals in Europe and in the USA between 1955 and 1963. SV40, a DNA virus of the family of papovaviridae, was proven to be oncogenic in rodents and able to transform human and animal cells in vitro. In 1993 SV40 was accidentally discovered to produce mesotheliomas in hamsters when it was injected in visceral cavities. Afterwards, SV40 DNA sequences were detected with significative frequency in human pleural mesotheliomas by using polymerase chain reaction (PCR) and then SV40 DNA oncogenicity was associated with its large T antigen (Tag). This finding was confirmed by many laboratories, while a few research groups failed to replicate these data and argued that the SV40 DNA detection might be a PCR contamination artefact. In this review the dispute is examined in the light of recent experiments performed to identify molecular and cellular aspects of carcinogenicity and/or co-carcinogenicity of SV40 in human mesothelioma.

Epidemiology of pleural mesothelioma in Italy.

The incidence of malignant mesothelioma (MM) in Italy is increasing and is assumed to be a consequence of high levels of asbestos exposure. Establishment of the National Mesothelioma Registry (ReNaM) and the co-operation of five regional centers has allowed the estimation of the incidence of malignant mesothelioma in major parts of Italy and the definition of exposure to asbestos.

Serum anti-p53 autoantibodies in pleural malignant mesothelioma, lung cancer and non-neoplastic lung diseases.

Alterations of the p53 gene may lead to the production of detectable autoantibodies (p53-Abs) in cancer patients. In order to evaluate the association of p53-Abs with pleuropulmonary diseases, four groups of subjects were analyzed by ELISA for serum p53-Abs, in the framework of a molecular epidemiologic study. Two of 30 pleural malignant mesothelioma patients (MM; 6.7%) and 8/48 lung cancer patients (LC; 16.7%) were seropositive, while all 51 healthy controls (HC) were negative. Two of 55 (3.6%) at-risk controls (RC) with non-malignant respiratory diseases were positive and were not subsequently diagnosed any cancer. The difference was statistically significant between LC and RC or HC (P = 0.01), but not between MM and any other group. No correlation was found with age, sex, cancer stage or histology, cigarette smoking or occupational exposure. A longer survival (not significant) was shown in seropositive LC but not in MM. p53 expression in tumor tissue was also evaluated in a subgroup of MM. In conclusion, the presence of detectable p53-Abs in serum was associated in a statistically significant proportion of cases with LC but only occasionally with MM. The longer survival among positive LC patients and the presence of two seropositive among patients with non-neoplastic respiratory diseases should be further investigated.

Implementation of a molecular epidemiology approach to human pleural malignant mesothelioma.

The carcinogenic effect of asbestos has been reported in the literature since 40 years, and early studies describing the epidemic occurrence of malignant mesothelioma (MM) in asbestos workers, have become a paradigm of occupational cancer research. Research on MM was abandoned for many years since MM was considered as an asbestos-related disease, interesting only from a perspective of disease control and preventive policies. The introduction of new biological endpoints in the epidemiological studies has boosted research in the field, providing new tools for the study of emerging priority in cancer research and in public health. This approach, known as molecular epidemiology has a great potential in the study of MM, contributing to the understanding of susceptibility factors, to the evaluation of cancer risk in people occupationally or environmentally exposed to carcinogens, and to the enhancement of diagnosis and therapy. A comprehensive approach based on the use of banks of biological samples is presented and its advantages discussed here. The application of innovative endpoints, such as oncoproteins in biologic fluids, genetic polimorphisms, or gene function is discussed, and relevant literature reviewed.

The role of chromoendoscopy in the surveillance of the duodenum of patients with familial adenomatous polyposis.

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.