Biomedical subjects

Stefano Ferretti

Publications and source records attributed to Stefano Ferretti.

13 recordsLinked to original sources

PubMed2006

Axillary lymph node nanometastases are prognostic factors for disease-free survival and metastatic relapse in breast cancer patients.

PURPOSE: Early breast cancer presents with a remarkable heterogeneity of outcomes. Undetected, microscopic lymph node tumor deposits may account for a significant fraction of this prognostic diversity. Thus, we systematically evaluated the presence of lymph node tumor cell deposits<or=0.2 mm in diameter [pN0(i+), nanometastases] and analyzed their prognostic effect. EXPERIMENTAL DESIGN: Single-institution, consecutive patients with 8 years of median follow-up (n=702) were studied. To maximize chances of detecting micrometastases and nanometastases, whole-axilla dissections were analyzed. pN0 cases (n=377) were systematically reevaluated by lymph node (n=6676) step-sectioning and anticytokeratin immunohistochemical analysis. The risk of first adverse events and of distant relapse of bona fide pN0 patients was compared with that of pN0(i+), pN1mi, and pN1 cases. RESULTS: Minimal lymph node deposits were revealed in 13% of pN0 patients. The hazard ratio for all adverse events of pN0(i+) versus pN0(i-) was 2.51 (P=0.00019). Hazards of pN1mi and pN0(i+) cases were not significantly different. A multivariate Cox model showed a hazard ratio of 2.16 for grouped pN0(i+)/pN1mi versus pN0(i-) (P=0.0005). Crude cumulative incidence curves for metastatic relapse were also significantly different (Gray's test chi2=5.54, P=0.019). CONCLUSION: Nanometastases are a strong risk factor for disease-free survival and for metastatic relapse. These findings support the inclusion of procedures for nanometastasis detection in tumor-node-metastasis staging.

Adult↗

PubMed2006

Molecular subtyping of breast cancer from traditional tumor marker profiles using parallel clustering methods.

PURPOSE: Recent small-sized genomic studies on the identification of breast cancer bioprofiles have led to profoundly dishomogenous results. Thus, we sought to identify distinct tumor profiles with possible clinical relevance based on clusters of immunohistochemical molecular markers measured on a large, single institution, case series. EXPERIMENTAL DESIGN: Tumor biological profiles were explored on 633 archival tissue samples analyzed by immunohistochemistry. Five validated markers were considered, i.e., estrogen receptors (ER), progesterone receptors (PR), Ki-67/MIB1 as a proliferation marker, HER2/NEU, and p53 in their original scale of measurement. The results obtained were analyzed by three different clustering algorithms. Four different indices were then used to select the different profiles (number of clusters). RESULTS: The best classification was obtained creating four clusters. Notably, three clusters were identified according to low, intermediate, and high ER/PR levels. A further subdivision in two biologically distinct subtypes was determined by the presence/absence of HER2/NEU and of p53. As expected, the cluster with high ER/PR levels was characterized by a much better prognosis and response to hormone therapy compared to that with the lowest ER/PR values. Notably, the cluster characterized by high HER2/NEU levels showed intermediate prognosis, but a rather poor response to hormone therapy. CONCLUSIONS: Our results show the possibility of profiling breast cancers by means of traditional markers, and have novel clinical implications on the definition of the prognosis of cancer patients. These findings support the existence of a tumor subtype that responds poorly to hormone therapy, characterized by HER2/NEU overexpression.

Adult↗

PubMed2006

HLA-G 14-bp polymorphism regulates the methotrexate response in rheumatoid arthritis.

OBJECTIVE: Methotrexate (MTX) represents the antirheumatic drug mainly used in rheumatoid arthritis (RA). HLA-G antigens are inducible nonclassical major histocompatibility complex class Ib molecules important for maintaining anti-inflammatory conditions. The HLA-G gene is characterized by a deletion/insertion polymorphism of 14 bp that controls specific mRNA stability and protein levels. It has been reported that MTX therapy mediates an increase of interleukin-10-producing cells. This cytokine up-regulates HLA-G expression. For this, we tested the hypothesis of an MTX-mediated HLA-G production and the possible relationship with the HLA-G 14-bp polymorphism. METHODS: Peripheral blood mononuclear cells from healthy individuals and non-MTX-treated RA patients were activated with different MTX concentrations, and soluble HLA-G (sHLA-G) and interleukin-10 production was investigated by specific immunoenzymatic assay. HLA-G 14-bp polymorphism genotyping was performed in healthy individuals and RA patients, defined as 'responders' and 'nonresponders' to the MTX therapy. RESULTS: MTX activation induces the production of sHLA-G molecules. A significant association was observed between the highest sHLA-G1 concentrations and the -14/-14 bp genotype. The analysis of the HLA-G 14-bp polymorphism in MTX-treated RA patients has confirmed an increase of the -14/-14 bp genotype in the responder group (chi=6.12, P=0.02; chi test) (odds ratio=2.46 (95% confidence interval, 1.26-4.84) P=0.009; logistic regression model). CONCLUSION: Our results propose that the MTX induces the production of the anti-inflammatory sHLA-G molecules that concur with the therapy response. Furthermore, the association between -14/-14 bp genotype and MTX clinical outcome proposes this polymorphism as a therapy marker in the early phases of the disease.

Aged↗

PubMed2006

Estimate of overdiagnosis of breast cancer due to mammography after adjustment for lead time. A service screening study in Italy.

INTRODUCTION: Excess of incidence rates is the expected consequence of service screening. The aim of this paper is to estimate the quota attributable to overdiagnosis in the breast cancer screening programmes in Northern and Central Italy. METHODS: All patients with breast cancer diagnosed between 50 and 74 years who were resident in screening areas in the six years before and five years after the start of the screening programme were included. We calculated a corrected-for-lead-time number of observed cases for each calendar year. The number of observed incident cases was reduced by the number of screen-detected cases in that year and incremented by the estimated number of screen-detected cases that would have arisen clinically in that year. RESULTS: In total we included 13,519 and 13,999 breast cancer cases diagnosed in the pre-screening and screening years, respectively. In total, the excess ratio of observed to predicted in situ and invasive cases was 36.2%. After correction for lead time the excess ratio was 4.6% (95% confidence interval 2 to 7%) and for invasive cases only it was 3.2% (95% confidence interval 1 to 6%). CONCLUSION: The remaining excess of cancers after individual correction for lead time was lower than 5%.

Aged↗

PubMed2005

In situ breast cancer: incidence trend and organised screening programmes in Italy.

The effect of mammography screening programmes on the incidence of in situ breast cancer (CIS) is described by analysis of the CIS incidence trend in the 1990s and comparison of pre-screening and screening periods in six areas of Italy. All 1069 CIS arising in women aged 40-79 years between 1988 and 1999 were analysed through age-standardised rates and Poisson regression models. The results show that, for the whole series, ductal carcinoma in situ (DCIS) represented 89% and lobular carcinoma in situ (LCIS) 11% of CIS detected. For all six areas, the introduction of screening increased the incidence of DCIS (screening/pre-screening ratio, range 1.12-1.77). Overall, DCIS represented 11% (226/2022) of all screening-detected cancers. A significant increasing trend in DCIS incidence during the 1990s and a modification in pattern of age-specific incidence rates after the beginning of screening programmes were observed. This increase can largely be explained by screening programmes. The incidence observed during the screening period was a persistent 39% higher than during the pre-screening period, after adjustment for the "percentage of cases diagnosed by screening". The increase also involves women at an age not targeted by screening programmes. In conclusion, as the increasing trend in DCIS is not completely explained by the effect of the screening programmes, this supports the use of mammography as a "spontaneous" preventive practice during ongoing organised screening programmes, particularly among age groups not usually invited for screening. Therefore, the effect of mammography on stage-specific incidence of CIS may be more marked than expected on the basis of the effect of screening programmes.

Adult↗

PubMed2005

Defective production of soluble HLA-G molecules by peripheral blood monocytes in patients with asthma.

BACKGROUND: HLA-G, a human nonclassic MHC class I molecule, is responsible for complex immunoinhibitory functions. HLA-G is expressed as membrane-bound and is secreted as soluble molecules by the peripheral blood CD14+ monocytes activated by IL-10. OBJECTIVE: It has been reported that LPS stimulation induces IL-10 production by PBMCs and that IL-10 levels are reduced in patients with severe asthma compared with patients with mild asthma and healthy subjects. The study was designed to investigate whether this impaired IL-10 production can affect the expression and the secretion of soluble HLA-G (sHLA-G)-1/HLA-G5 molecules. METHODS: We investigated the production of sHLA-G1/HLA-G5 and IL-10 by specific ELISAs in the culture supernatants of LPS-activated PBMCs from 24 healthy subjects and 20 patients with moderate to severe persistent asthma. RESULTS: LPS stimulation induced the secretion of IL-10 and sHLA-G1/HLA-G5 molecules in all healthy subjects, whereas in patients with asthma, the levels of IL-10 were significantly lower (P < .001) and the number of cultures exhibiting detectable sHLA-G1/HLA-G5 was reduced (7/20; P < .001). The addition of exogenous IL-10 to LPS-stimulated PBMCs from patients with asthma restored normal sHLA-G1/HLA-G5 production. CONCLUSION: Our data suggest that a specific deficit of IL-10 secretion in patients with asthma could prevent the normal production of sHLA-G1/HLA-G5 molecules. The reduction of immunosuppressive activity mediated by HLA-G could in turn contribute to the persistence of chronic airway inflammation in asthma.

Adult↗

PubMed2005

Confirmatory tests in the diagnosis of brain death: comparison between SPECT and contrast angiography.

OBJECTIVE: Cerebral blood flow tests have increasingly been advocated for the confirmation of brain death (BD). Four-vessel angiography has been considered the most reliable investigation in the diagnosis of BD for >30 yrs, but it is invasive. (99m)Tc-HMPAO SPECT provides noninvasive, multiplanar imaging of brain tissue perfusion. The aim of this study was to check the reliability of SPECT compared with contrast angiography. DESIGN: Prospective, blind study. SETTING: Neurointensive care unit of a university hospital. PATIENTS: Consecutive clinically brain dead patients with flat electroencephalogram. INTERVENTIONS: BD was diagnosed according to Italian law. (99m)Tc-HMPAO SPECT and four-vessel angiography were performed in the same session; the rater of each investigation ignored the results of the other. Blood pressure, Sp(O2), and P(ECO2) were monitored throughout the study: any episode of hypoxia or hypotension caused exclusion of the patient from the study. MEASUREMENTS AND MAIN RESULTS: Twenty brain dead patients were enrolled. The cause of BD was head injury in seven cases (35%), subarachnoid hemorrhage in seven (30%), spontaneous hemorrhage in one (10%), brain tumors in two (10%), stroke in two (10%), and thrombosis of the sagittal sinus in one (5%). Both angiography and SPECT confirmed BD in 19 of 20 patients: angiography showed the absence of filling of intracranial arteries, while SPECT showed a picture of "empty skull." For the remaining patient, angiography showed slight and late filling of left vertebral, basilar, and posterior cerebral arteries, while SPECT showed faint traces of uptake in the posterior fossa on the right side and on the midline. For this patient, the tests were repeated 48 hrs later, and both showed the arrest of intracranial circulation, thus confirming BD. CONCLUSIONS: Our results confirm the reliability of SPECT in the diagnosis of BD; because SPECT is noninvasive, it is a good candidate for the "gold standard" of diagnosis.

Adult↗

PubMed2003

Incidence of AIDS-defining cancers after AIDS diagnosis among people with AIDS in Italy, 1986-1998.

A record linkage was carried out between the Italian National Registry of AIDS and 19 cancer registries. The aim was to evaluate the 1986 through 1998 trends in incidence rate (IR) of AIDS-defining cancers (ADCs) among persons with AIDS (PWA) in Italy overall and according to various characteristics. A steady decrease in IRs was found for Kaposi sarcoma (KS) in men between 1986-1992 (2.5 per 100 person-years [py]) and 1997-1998 (1.0 per 100 py). Conversely, the first decrease in IRs of KS in women (from 0.9 to 0.6 per 100 py) and of non-Hodgkin lymphoma in both genders (from 1.7 to 0.7 per 100 py) was seen between 1993-1996 and 1997-1998, thus pointing to a favorable impact of highly active antiretroviral therapies. The decline was consistent across different age and HIV transmission groups, but it was more marked in PWA with a CD4 count >50 cells/microL than in PWA with more severe immune suppression. As a proportion of AIDS cases, invasive cervical cancer increased from 1.5% in 1993-1996 to 2.4% in 1997-1998, but IRs after AIDS could not be evaluated. On account of the marked decline of KS in men in 1997-1998, the overall burden of ADCs in Italy became similar in both genders.

AIDS-Related Opportunistic Infections↗

PubMed2002

Stage-specific incidence of breast cancer before the beginning of organized screening programs in Italy.

OBJECTIVE: To measure stage-specific geographic and time variability of breast cancer in seven Italian areas before the onset of organized screening programs. METHODS: All invasive cancers (8689 cases) arising in women aged 40-79 years during the pre-screening period 1985-1997, were considered. Multiple Poisson regression analysis was performed. RESULTS: About 39% of the cases were classified as "early," 52% as "advanced," and 9% as "unspecified" stage. Age-adjusted incidence rates showed a significant geographic variation for early but not for advanced cancers (range: 58-103 cases/100,000 and 104-125 cases/100,000, respectively). The result was confirmed in the multiple regression analysis after adjustment for year of diagnosis and age. Early breast cancer risk adjusted for age and registry showed a significant increase over time (+3.9% per year for all ages, and +6.2% per year for age category 50-79). In contrast, a decreasing time trend was observed for advanced cancer of 3 cm or over in women aged less than 60. CONCLUSIONS: In our study, early breast cancer incidence varied both by geographic area and time before the commencement of screening. The differences in early-stage incidence may well be related to differences in availability of "spontaneous" mammography. Late-stage incidence decreased over time in younger women and for very advanced cases, but not in the older ones, nor for cancers less than 3 cm. Early detection outside organized screening was only partially efficient in reducing advanced breast cancer incidence. The trend of incidence of advanced disease, as previously proposed, is confirmed to be a valid early indicator of effectiveness of screening.

Adult↗

PubMedDate not supplied

National estimates of cancer patients survival in Italy: a model-based method.

AIMS AND BACKGROUND: To provide model-based estimates of all cancers patient survival in Italy and in Italian large geographical areas (North-West, North-East, Center, South), where only partial coverage of cancer registries data is available, and to describe them in terms of time trends. Moreover, to measure the degree of representativeness of cancer patient survival obtained from Italian cancer registries data. METHODS: Relative survival in the four main Italian geographical areas was estimated by a parametric mixture model belonging to the class of "cure" survival models. Data used are from Italian cancer registries, stratified by sex, period of diagnosis and age. The Italian national survival was obtained as a weighted average of these area-specific estimates, with weights proportional to the number of estimated incident cases in every area. The model takes into account also differences in survival temporal trends between the areas. RESULTS: Relative survival for all cancers combined in Italian patients diagnosed in 1990-1994 was estimated to be higher in women (53%) than in men (38%) at 5 years from the diagnosis. The survival trend is increasing by period and decreasing by age, both for men and women. The greatest gain in terms of survival was obtained by the elderly, with annual mean growth rates in the period 1978-1994 equal to 3.5% and 3.2% for men and women, respectively. More than 50% of the youngest cancer patients were "cured", whereas for the elderly this proportion dropped to 15% and 25% for men and women, respectively. The South of Italy had the lowest survival and the North the most pronounced increase. CONCLUSIONS: The obtained national survival estimates are similar, but not identical, to previously published estimates, in which Italian registries' data were pooled without any adjustment for geographical representativeness. The four Italian areas have different survival levels and trends, showing variability within the country. The differences in survival between men and women may be explained by the different proportion of lethal cancers. Among males, most cases had a poor prognosis (lung and stomach cancers), whereas among females the largest proportion was made up of curable and less lethal cancers (breast cancer).

Adolescent↗

PubMedDate not supplied

Cancer trends in Italy: figures from the cancer registries (1986-1997).

The Italian Network of Cancer Registries analyzed incidence and mortality cancer trends during the period 1986-1997 Overall, 525,645 incident cancers and 269,902 cancer deaths (in subjects 15 years and older) were included. Age-adjusted rates, joinpoints (points in time where trend significantly changes from linearity) and estimated annual percent changes in rates (EAPC) were computed. Overall cancer incidence was significantly increasing in both sexes and cancer mortality was significantly decreasing (since 1991 among males). Incidence and mortality trends are summarised for single cancer sites. Crude rates are also showed to evaluate the effect of population ageing in terms of diagnostic and therapeutic burden for the National Health System.

Adolescent↗

PubMedDate not supplied

Quality and completeness indices.

In the present study, time trends of the main quality indices in the pool of the Italian Network of Cancer Registries (pool AIRT) are presented for the period 1986-1997. The percentage of cases with morphological verification increased from 75% to 83% among males and from 77% to 85% among females. Cases known only from death certificates (DCO) decreased over time in both sexes; in recent years they were about 3% of the whole case-series. Mortality incidence ratio decreased over time, from 66% to 54% among males and from 55% to 48% among females. Also cases with unknown primary site showed a decreasing time tendency. Such quality indices are also presented for specific cancer sites and for elderly subjects (75+ years). The overall trends of quality indices showed an improvement in both the activity of Cancer Registries and of the Health System.

Aged↗

PubMedDate not supplied

Upper gastrointestinal tract cancers: oesophagus, stomach, liver, gallbladder and biliary ducts, pancreas.

In this paper temporal trend of the upper gastrointestinal tract cancers in the Italian Network of Cancer Registries (pool AIRT) are analysed during the period 1986-1997. Oesophagus cancer (4477 cases and 4226 deaths analysed) showed a decrease in incidence rates that was statistically significant among males and less evident in recent years among females. Mortality is significantly decreasing both among males (since 1993) and females. Stomach cancer (34282 cases and 26430 deaths) had a stable decreasing trend, in both sexes, for both incidence which decreased at a rate of more 3% every year, and of mortality, mean annual rate decrease over 4%. As regards liver cancer (13893 cases 13655 deaths) an increasing incidence trend (up to 1993 among males) has been documented; mortality was stable. Cancers of the biliary tract (6662 cases and 5065 deaths) showed stable rates both in incidence (slightly decreasing among females) than in mortality. Pancreas cancer (13300 cases and 12937 deaths) presented increasing incidence in both sexes with stable mortality rates.

Aged↗