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Rosangela Filiberti

Publications and source records attributed to Rosangela Filiberti.

At least 19 recordsLinked to original sources
PubMed2006

Decline in serum carcinoembryonic antigen and cytokeratin 19 fragment during chemotherapy predicts objective response and survival in patients with advanced nonsmall cell lung cancer.

BACKGROUND: The authors assessed the predictive and prognostic role of decline in the serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA 21-1) during chemotherapy in patients with advanced nonsmall cell lung cancer (NSCLC). METHODS: Changes in serum levels of CEA and CYFRA 21-1 during first-line, conventional chemotherapy were studied prospectively with an immunometric assay at baseline and every 2 courses in 117 patients with advanced NSCLC. Data were correlated with radiologic objective response (OR) and survival. RESULTS: One hundred seven patients were evaluable for radiologic and serologic response assessment after 2 chemotherapy courses. The radiologic OR rate was 44% overall. The CEA and CYFRA 21-1 responses (> or =20% reduction over baseline level; assessed after the second course of chemotherapy) were 38% and 61%, respectively. Statistically significant correlations were observed between CEA and CYFRA 21-1 responses and OR (P = .01 and P = .004, respectively). The median survival from response assessment (landmark analysis) was 9 months. In a univariate analysis, disease stage, performance status, baseline lactate dehydrogenase level (LDH), OR, CEA response, and CYFRA 21-1 response were correlated significantly with survival. In particular, the median survival was 13 months for patients who had a CEA response and 11 months for patients who had a CYFRA 21-1 response compared with 8 months and 6 months for patients who did not respond, respectively. In a multivariate analysis, performance status (P = .005), baseline LDH level (P = .02), CEA response (P = .03) and CYFRA 21-1 response (P = .01) were confirmed as independent prognostic factors for survival. CONCLUSIONS: CEA and CYFRA 21-1 responses appeared to be reliable surrogate markers of chemotherapy efficacy in patients with advanced NSCLC.

Adult↗
PubMed2006

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.

Aged↗
PubMed2006

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.

Arylamine N-Acetyltransferase↗
PubMed2006

Endoscopic mucosal resection.

Endoscopic mucosal resection (EMR) is a promising therapeutic option for removal of superficial carcinomas or premalignant lesions throughout the gastrointestinal tract. This review discusses indications and the several techniques of EMR in early tumors of esophagus, stomach, duodenum, and colon. EMR is not yet widely utilized in the West. However, great benefits may be obtained from this non-invasive technique after an accurate evaluation of patients and a careful staging of lesions that may assess the depth of infiltration and exclude the presence of lymph node metastases. EMR permits a complete removal of the lesion with histologic assessment of the entire specimen and the change in the pathologic stage in a significant number of patients. To minimize the risk of serious complications (mostly bleeding and perforation), only experienced endoscopists should undertake EMR in an appropriate environment. Data from literature are encouraging on the use of EMR, but a long-term follow-up of a large number of patients is necessary to confirm the effectiveness of this therapy.

Endoscopy, Gastrointestinal↗
PubMed2006

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.

Aged↗
PubMed2006

Mucosectomy for high-grade dysplasia in Barrett's esophagus.

Reports on the natural history of high-grade dysplasia (HGD) are sometimes contradictory, but suggest that 10-30% of patients with HGD in Barrett's esophagus (BE) will develop a demonstrable malignancy within five years of the initial diagnosis. Surgery has to be considered the best treatment for HGD or superficial carcinoma, but is contraindicated in patients with severe comorbidities. Non-surgical treatments such as intensive endoscopic surveillance, endoscopic ablative therapies, and endoscopic mucosal resection (EMR) have been proposed. EMR is a newly developed procedure promising to become a safe and reliable non-operative option for the endoscopic removal of HGD or early cancer within BE. It is important to assess the depth of invasion of the lesion and lymph node involvement before choosing EMR. This technique permits more effective staging of disease obtaining a large sample leading to a precise assessment of the depth of malignant invasion. Complications such as bleeding and perforation may occur, but can be treated endoscopically. Trials are needed to compare endoscopic therapy with surgical resection to establish clear criteria for EMR and ablative therapies.

Barrett Esophagus↗
PubMed2006

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.

Adenocarcinoma↗
PubMed2005

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.

Aged↗
PubMed2005

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.

Asbestos↗
PubMed2005

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.

Aged↗
PubMed2005

Endoscopic treatment of high-grade dysplasia and early cancer in Barrett's oesophagus.

Barrett's oesophagus is the premalignant precursor of oesophageal adenocarcinoma. Non-dysplastic metaplasia can progress to low-grade dysplasia, high-grade dysplasia, and finally to invasive cancer. Although the frequency of adenocarcinoma in patients with Barrett's oesophagus is low, surveillance is justified because the outcome of adenocarcinoma is poor. Oesophagectomy remains the standard treatment for patients with high-grade dysplasia and superficial carcinoma. However, it has been associated with substantial morbidity and mortality and some patients are judged unfit for surgery. In this review, the present status of less invasive procedures is discussed. Endotherapy preserves the integrity of the oesophagus and allows a better quality of life to patients at low risk of developing lymph-node metastases. Opposition to endoscopic treatment is based mainly on the identification of undetected foci of cancer and high-grade dysplasia in oesophagectomy samples. The current ablative techniques used are photodynamic therapy, argon plasma coagulation, laser treatment, and endoscopic mucosal resection.

Adenocarcinoma↗
PubMed2004

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.

Aged↗
PubMed2004

EMR of large sessile colorectal polyps.

BACKGROUND: EMR optimizes histopathologic assessment of resected lesions. This study evaluated the outcome of EMR of large sessile colorectal polyps in terms of complications and recurrence. METHODS: An uncontrolled prospective study was conducted of a cohort of 136 patients with sessile colorectal polyps referred for EMR. After submucosal injection, EMR was performed piecemeal by either snare polypectomy alone or with cap aspiration. RESULTS: In 136 patients, a total of 139 sessile polyps were resected, 86 of which were in the right colon. Median polyps diameter was 20 mm in the right colon and 30 mm in the other colonic segments. Intraprocedure bleeding occurred after 15 polypectomies (10.8%) and was controlled endoscopically in all cases; there was no delayed bleeding. Post-polypectomy syndrome occurred in 5 patients (3.7%). There was no perforation. Invasive carcinoma was found in 17 sessile colorectal polyps, and surgery was performed in 10 of 17 cases. Follow-up colonoscopy in 93 patients without invasive carcinoma (96 polyps), over a median of 12.3 months, disclosed local recurrence of 21 adenomatous polyps (21.9%). Colonoscopic follow-up in 5 of the 7 patients, who had sessile colorectal polyps with invasive carcinoma and did not undergo surgery, disclosed no local recurrence. CONCLUSIONS: EMR, including EMR with cap aspiration, is effective and safe for removal of sessile colorectal polyps throughout the colon.

Adenocarcinoma↗
PubMed2003

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.

Asbestos↗
PubMed2003

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.

Aged↗
PubMed2003

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.

Adenocarcinoma↗