Biomedical subjects

S Ferretti

Publications and source records attributed to S Ferretti.

At least 19 recordsLinked to original sources

PubMed2006

Mastectomy rates are decreasing in the era of service screening: a population-based study in Italy (1997-2001).

We enrolled all 2162 in situ and 21 148 invasive cases of breast cancer in 17 areas of Italy, diagnosed in 1997-2001. Rates of early cancer increased by 13.7% in the screening age group (50-69 years), and breast conserving surgery by 24.6%. Advanced cancer rates decreased by 19.4%, and mastectomy rates by 24.2%. Service screening did not increase mastectomy rates in the study population.

Aged↗

PubMed2006

Bisphosphonates and jaw osteonecrosis in patients with advanced breast cancer.

BACKGROUND: In recent years, several cases of mandibular necrosis associated with long-term use of bisphosphonates have been reported. The estimated incidence varies from 1% to 4.6%. PATIENTS AND METHODS: We conducted an observational study with the aim of determining the incidence of jaw osteonecrosis in advanced breast cancer patients with bone metastases under bisphosphonate treatment and to identify subjects at higher risk of developing this complication evaluating preclinical signs. We considered two groups of patients. All the patients complaining of odontostomatological symptoms underwent maxillary CT scan and maxillo-surgeon clinical examination. Asymptomatic patients were asked to perform a standard orthopantomography (OPT). RESULTS: From February 2005 to October 2005, we observed five patients with jaw bone necrosis (6%). Diagnosis was radiological and clinical. In two patients a confirmatory biopsy was performed. In the same time interval, OPTs were collected from 76 asymptomatic patients. Three OPTs revealed radiological features of suspicious mandibular necrosis. Maxillary CT scan confirmed the presence of an osteolityc area with signs of periosteal reaction. All the three patients were referred to maxillo-surgeon and two out of three patients underwent mandibular biopsy, but histopathological results were not conclusive. CONCLUSIONS: In our experience, the incidence of jaw bone necrosis in breast cancer patients seems to be higher than in other reports (6%). Radiological features of suspicious jaw necrosis were observed in three asymptomatic patients. We do not know how these findings should be considered. Anyway, standard OPT is a simple procedure, and may allow identification of periodontal conditions that in some way can predispose to the development of this uncommon event.

Adult↗

PubMed2005

Classic Kaposi's sarcoma in Italy, 1985-1998.

To evaluate incidence rates (IRs) of classic Kaposi's sarcoma (CKS) in Italy after the spread of AIDS, we distinguished CKS from AIDS-related KS (AKS) using an 'ad hoc' record linkage procedure between 15 Cancer Registries (CRs) (21% of the Italian population) and the national AIDS Registry. Between 1985 and 1998, 874 cases of CKS and 634 cases of AKS were diagnosed in the study areas. CKS accounted for 16 and 27% of KS cases below 55 years of age in men and women, respectively, but for 91 and 100% of those above age 55. The IRs for CKS were 1.0/ in men and 0.4/100,000 in women, but they varied between 0.3 in Umbria and 4.7 in Sassari in men, and between 0.1 in Parma and 1.7 in Sassari in women. IRs of CKS in both genders were stable between 1985-1987 and 1993-1998. In Northern and Central CRs the IR (adjusted for age and gender) for CKS was 0.5 in individuals born in the same area, but 1.6 in individuals born in Southern Italy or in the Islands (rate ratio = 3.2) suggesting that KS-associated herpesvirus, the cause of KS, is acquired early in life.

Acquired Immunodeficiency Syndrome↗

PubMed2005

Screen-detected vs clinical breast cancer: the advantage in the relative risk of lymph node metastases decreases with increasing tumour size.

Screen-detected (SD) breast cancers are smaller and biologically more indolent than clinically presenting cancers. An often debated question is: if left undiagnosed during their preclinical phase, would they become more aggressive or would they only increase in size? This study considered a registry-based series (1988-1999) of 3329 unifocal, pT1a-pT3 breast cancer cases aged 50-70 years, of which 994 were SD cases and 2335 clinical cases. The rationale was that (1) the average risk of lymph node involvement (N+) is lower for SD cases, (2) nodal status is the product of biological aggressiveness and chronological age of the disease, (3) for any breast cancer, tumour size is an indicator of chronological age, and (4) for SD cases, tumour size is specifically an indicator of the duration of the preclinical phase, that is, an inverse indicator of lead time. The hypothesis was that the relative protection of SD cases from the risk of N+ and, thus, their relative biological indolence decrease with increasing tumour size. The odds ratio (OR) estimate of the risk of N+ was obtained from a multiple logistic regression model that included terms for detection modality, tumour size category, patient age, histological type, and number of lymph nodes recovered. A term for the detection modality-by-tumour size category interaction was entered, and the OR for the main effect of detection by screening vs clinical diagnosis was calculated. This increased linearly from 0.05 (95% confidence interval: 0.01-0.39) in the 2-7 mm size category to 0.95 (0.64-1.40) in the 18-22 mm category. This trend is compatible with the view that biological aggressiveness of breast cancer increases during the preclinical phase.

Aged↗

PubMed2004

Patupilone (epothilone B, EPO906) and imatinib (STI571, Glivec) in combination display enhanced antitumour activity in vivo against experimental rat C6 glioma.

PURPOSE: The microtubule-stabilizing agent patupilone (epothilone B, EPO906) and the tyrosine kinase inhibitor imatinib (STI571, Glivec) which primarily inhibits Bcr-Abl, PDGF and c-Kit tyrosine kinase receptors, were combined in vivo to determine if any interaction would occur with respect to antitumour effect and tolerability using rat C6 glioma xenografted into nude mice. METHODS: Patupilone and imatinib were administered alone or in combination at suboptimal doses. Imatinib treatment (orally once daily) was initiated 4 days after s.c. injection of rat C6 glioma cells into athymic nude mice and patupilone administration (i.v. once per week) was started 3 or 4 days after imatinib treatment. RESULTS: As a single agent, imatinib was inactive in the regimens selected (100 mg/kg: T/C 86% and 116%; 200 mg/kg: T/C 68% and 84%; two independent experiments), but well tolerated (gain in body weight and no mortalities). Patupilone weekly monotherapy demonstrated dose-dependent antitumour effects (1 mg/kg: T/C 67% and 70%; 2 mg/kg: T/C 32% and 63%; 4 mg/kg: T/C 3% and 46%). As expected, dose-dependent body weight losses occurred (final body weight changes at 1 mg/kg were -7% and -3%; at 2 mg/kg were -23% and -13%; and at 4 mg/kg were -33% and -15%). Combining 2 mg/kg patupilone and 200 mg/kg per day imatinib in one experiment produced a non-statistically significant trend for an improved antitumour effect over patupilone alone (combination, T/C 9%), while in the second experiment, enhancement was seen with the combination and reached statistical significance versus patupilone alone (combination, T/C 22%; P=0.008). Reduction of the imatinib dose to 100 mg/kg per day resulted in no enhancement of antitumour activity in combination with 2 mg/kg patupilone. Reduction of the patupilone dose to 1 mg/kg resulted in a reduced antitumour effect, and only a trend for synergy with either imatinib dose (combination, T/C 46% and 40%). Pooling the data from the two experiments confirmed a significant synergy for the combination of 2 mg/kg patupilone and 200 mg/kg per day imatinib (P=0.032), and a trend for synergy at the 1 mg/kg patupilone dose. Reduction in the imatinib dose to 100 mg/kg per day resulted only in additivity with either dose of patupilone. Body weight losses were dominated by the effect of patupilone, since no greater body weight loss was observed in the combination groups. CONCLUSION: Combining patupilone with high-dose imatinib produced an increased antitumour effect without affecting the tolerability of treatment in a relatively chemoresistant rat C6 glioma model. Such results indicate that further evaluation is warranted, in particular to elucidate possible mechanisms of combined action.

Animals↗

PubMed2004

Low-dose intramuscular hepatitis B immune globulin and lamivudine for long-term prophylaxis of hepatitis B recurrence after liver transplantation.

The combination of lamivudine and hepatitis B immunoglobulins (HBIg) to prevent recurrence of HBV hepatitis has significantly improved the survival of patients transplanted for HBV-related end-stage liver disease. Generally, HBIg are administered intravenously. We evaluated the efficacy, tolerability, and cost savings of long-term intramuscular HBIg and lamivudine in 28 patients (23 men and 5 women), who received liver transplants for acute or chronic HBV-related liver disease. Twelve patients started lamivudine before and 16 at the time of liver transplantation. HBIg were administered intravenously during the first week (50 to 70,000 IU) and intramuscularly thereafter (1200 IU every 3 to 6 weeks) to maintain an HbsAb titer >100 IU/L. Mean follow-up was 20 +/- 13 months. Only one patient experienced HBV recurrence (9 months after transplantation). This patient had failed to follow the scheduled prophylaxis. Cumulative survival at 3 years was 83%. Intramuscular HBIg were well tolerated in all cases. Cost analysis comparing intramuscular vs intravenous HBIg administration showed that 39,490 Euros were saved per patient per year. These preliminary results show that low-dose intramuscular HBIg and lamivudine are efficacious and cost-effective for long-term prophylaxis of hepatitis B recurrence after liver transplantation.

Antiviral Agents↗

PubMed2004

Population-based incidence and mortality cancer trends (1986-1997) from the network of Italian cancer registries.

The objective of this study was to analyse incidence and mortality cancer trends in the Italian Network of Cancer Registries (about 8,000,000 inhabitants) during the period 1986-1997. Included were 525,645 newly diagnosed cancers and 269,902 cancer deaths (subjects > 14 years). Joinpoints (points in time where trend significantly changes from linearity) were found and estimated annual percentage changes (EAPC) used to summarize tendencies. Overall cancer incidence increased in both sexes and cancer mortality significantly decreased (since 1991 among men). Lung cancer showed significantly decreasing incidence (EAPC = -1.4%) and mortality (EAPC = -1.6%) among men and increasing trends among women. In women, breast cancer incidence significantly increased (EAPC= +1.7%) and mortality decreased since 1989 (EAPC= -2.0%). Stomach cancer incidence and mortality decreased in both sexes. Prostate incidence sharply increased since 1991 and mortality decreased. Colon cancer incidence increased and rectum mortality decreased significantly in both sexes. Significant increases in incidence were also found for kidney (up to 1991 among men), urinary bladder, skin epithelioma, melanoma, liver (up to 1993 among men), pancreas, mesothelioma, Kaposi's sarcoma (up to 1995 among men), testis, thyroid, non-Hodgkin's lymphomas and multiple myeloma. Mortality significantly decreased for cancers of the oral cavity and pharynx, oesophagus, liver (women), larynx (men), bone, cervix (since 1990), central nervous system, urinary bladder, thyroid, Hodgkin's lymphomas and leukaemias (men). Non-Hodgkin's lymphoma mortality increased in both sexes. In conclusion, most of the changes seen can be explained as the effect of changes in smoking habits and of the extension of secondary prevention activities. The Italian health care system will also have to cope with growing cancer diagnostic and therapeutic needs due to population ageing.

Age Distribution↗

PubMed2003

The impact of organised screening programmes on the stage-specific incidence of breast cancer in some Italian areas.

The aim of this study was to examine the effects of mammographic screening programmes on stage-specific incidence of breast cancer. The study compared prescreening and screening periods in seven areas in Italy, primarily evaluating the first screening round. All 17617 breast cancers (16554 invasive, 1063 in situ) registered in women aged 40-79 years between 1988 and 1999 were analysed through age-standardised rates and Poisson regression models. For all areas, independent of the baseline rates, the introduction of screening increased incidence for invasive cancers overall and, more markedly, for early cancers (screening/prescreening ratio: range 1.07-1.47 and 1.23-1.82, respectively), modifying the pattern of age-specific rates. The multiple regression analysis showed that the percentage of cases diagnosed at screening explained most of the increase; a residual effect of diagnosis period (screening versus prescreening) suggested a role for 'spontaneous' early detection in ages outside of the screening programme. Advanced cases did not show consistent variations across the registries for those aged 40-79 years (range: 0.91-1.21), whereas a more coherent picture was observed for those aged 50-69 years. In one area, a moderate reduction in the number of 'advanced' cases in the second screening period was observed. For all stages, the age-specific incidence rates of cases diagnosed outside of the screening programme for the age groups 50-69 years were lower than the corresponding rates in the prescreening period, suggesting a shift from the usual clinical services to the screening programme. Our results confirmed the increase in early-stage cancers occurring at the start of screening, and substantially explained the rise in breast cancer incidence. In addition, our study confirms the importance of cancer registries in monitoring the effect of breast cancer screening and the validity, for this purpose, of the linkage between cancer registries and screening programme databases.

Adult↗

PubMed2002

Ultrastructural basis for the efficiency of an ileal orthotopic neobladder 27 years after surgery.

The morphological and functional basis of the excellent clinical outcome of ileal orthotopic neobladders are largely unknown. Only long-term follow-up studies will provide an adequate answer to this unsettled question. We have studied a patient who underwent this type of surgery over 27 years ago. Besides an important secretive adaptation we have found, at the ultrastructural level, that the monolayered epithelium does not show signs of true metaplasia and that changes had occurred in the intercellular junctions, namely that desmosomes are significantly increased. Although limited to a single case, these features, if confirmed by further observations, suggest a working hypothesis for the understanding of the definitive phenotypic adaptation of the ileal epithelium to the new aggressive environment.

Aged↗

PubMed2001

Non-Hodgkin lymphoma among young adults with and without AIDS in Italy.

To compare the presentation and prognosis of non-Hodgkin lymphoma (NHL) in people with AIDS (PWA) and in the general Italian population, a record linkage study was carried out. The fraction of NHLs attributable to HIV/AIDS was also estimated. Information from the National AIDS Registry (RAIDS) was linked with records from 13 cancer registries (CR), covering about 15% of the Italian population. During the period 1985--94, among PWA ages 15--49, 136 NHLs were identified (8% of all NHLs) and were compared with 1,481 concurrent incident NHL cases of the same age group among non-PWA. Percentages above 13% of all NHLs were registered in the northern areas of Genoa and Varese, i.e., the most heavily affected by the AIDS epidemic. Between 1 year prior to and 3.5 years after AIDS diagnosis, PWA showed an overall standardised incidence ratio (SIR) for NHL of 302. SIR was particularly high (394) within 3 months after AIDS diagnosis and subsequently declined to 170. SIR was somewhat higher in females (428) than in males (280) but similar among intravenous-drug users (299) and other HIV-transmission groups (309). High-grade NHL, particularly immunoblastic and Burkitt's lymphoma, were twice as frequent among PWA than non-PWA. Conversely, low-grade NHL were less frequent. Except for the high proportion of brain localisation, no clear difference emerged in the pattern of NHL presentation site in PWA compared with non-PWA. At variance with NHL in the general population, among PWA histological grade had little impact on survival, which overall appeared to be very poor (2-year survival: 10%; 95% confidence interval: 3%--17%). Our present linkage of RAIDS and CRs represents an efficient tool for the surveillance of trends in incidence and survival of NHL among PWA in Italy.

Adolescent↗

PubMed2001

Vesical continence in bilateral ectopic single ureters.

PURPOSE: We explore the possibility of gaining suitable vesical capacity and continence in bilateral single ureters without having to resort to urinary diversion or bladder neck reconstruction. MATERIALS AND METHODS: In the last 10 years we treated 6 girls with bilateral ectopic ureters, and 2 with a single kidney and urethral ectopic ureter. Both ureters were ectopic in the urethra in 3 cases, and 1 ureter was inserted in the urethra and 1 in the bladder neck in the other 3. Preoperative examinations included ultrasonography, cystography, excretory urography and endoscopy in all cases, and magnetic resonance imaging in 2. Patient age at intervention ranged from 1 month to 8 years. RESULTS: Cross-trigonal reimplantation of the ectopic ureters through a correctly positioned neomeatus was performed in 7 cases. In 2 patients it was impossible to reach the ureteral insertion from inside the bladder (1 ureter in 1 and both ureters in 1), and so the distal tract of these ureters was resected extravesically as close as possible to the urethra. One patient with a single kidney also had an anorectal malformation and a rectovaginal fistula. She had pelvic renal ectopia and the ureter was inserted beneath the urogenital diaphragm causing minimal bladder capacity. Therefore, a sigmoid neobladder with appendicostomy was constructed according to the Mitrofanoff principle. A Young-Dees bladder neck plasty was done in 2 patients at the same time as ureteral reimplantation and 3 years later in 1. Followup urodynamics revealed more than acceptable continence. Bladder capacity was insufficient in only 1 polyuric patient. CONCLUSIONS: A bladder with bilateral ureteral ectopia is not necessarily useless, and the majority of patients can achieve normal bladder function and capacity along with normal transurethral voiding and satisfactory continence.

Choristoma↗

PubMed2001

Biophenotypes and survival of BRCA1 and TP53 deleted breast cancer in young women.

The aim of this study was to examine the loss of heterozygosity (LOH) of BRCA1 (17q21) and TP53 (17p13.1) in early-onset breast cancer patients; to correlate biopathological characteristics with molecular alterations; and to investigate the survival of LOH-related cancers. BRCA1 and TP53 LOH were evaluated in 78 early-onset breast cancers (< or = 40 years, Group 1) and 80 patients with age > 55 years (Group 2). Cases were characterized for multiple biological markers (ER, PR, proliferation index (PI), NEU and p53). LOH was carried out on microdissected paraffin embedded tissues; microsatellites D17S855 (BRCA1) and D17S786 (TP53) were amplified by fluorescent PCR and analyzed by an automated DNA sequencer. Early-onset breast cancers showed a higher frequency of ductal histotype (89.7% vs. 56.3% p < 0.001), node-positive (53.8% vs. 38.7%), larger size (p = 0.017), higher mitotic rate (p = 0.025), higher nuclear and final grade (p = 0.01 and p = 0.001, respectively). D17S855 LOH was 32.8% in group 1 vs. 21% in group 2; D17S786 LOH was 50.7% vs. 31.3% (p = 0.03), respectively. BRCA1 LOH was correlated with higher PI (p = 0.032) and higher p53 expression (p < 0.001) in group 1 and with higher NEU expression (p = 0.028) in group 2. TP53 LOH was correlated with p53 overexpression (p = 0.03) in group 1. A worse clinical outcome in early-onset LOH related cancers emerged from follow-up data: TP53 and BRCA1 LOH were associated with a shorter relapse free interval (RFI) (p = 0.03) and a poorer overall survival (OS) (p = 0.04), respectively. This study underlines different biological profiles in the two age groups investigated, probably reflecting different mechanisms of carcinogenesis. In accordance with adverse histopathological features in early-onset patients, LOH-related cancers have an unfavorable prognosis.

Adult↗

PubMed2001

Aggressive angiomyxoma of the spermatic cord. Two unusual cases occurring in childhood.

We report on two cases of aggressive angiomyxoma (AAM) of the spermatic cord occurring in two 13-year-old children. Clinically, the tumor simulated a mass of the spermatic cord. Histologically, it represented a poorly circumscribed, benign myxoid tumor, with a sparse population of stromal cells immunoreactive for vimentin and, focally, for smooth muscle actin. No immunostaining for desmin, S-100, p53, p21waf-1, c-Erb-B2 and estrogen-progesterone receptors was found. High proliferating cell nuclear antigen (PCNA) immunoexpression found in most of the tumor cells may explain the high risk of recurrence. AAM should be considered in the differential diagnosis of a spermatic cord mass occurring during infancy.

Adolescent↗

PubMed2001

One shot: a novel method to dilate the nephrostomy access for percutaneous lithotripsy.

BACKGROUND AND PURPOSE: The creation of the nephrostomy access is a fundamental step of percutaneous nephrolithotripsy (PCNL). Dilation of the track is usually achieved with multiple incremental flexible exchange dilators of the Amplatz type, metal telescoping dilators of the Alken type, or a balloon. Currently, balloon dilation is regarded as the most modern and safest system, though it has the disadvantage of relatively high cost. The aim of this study was to demonstrate that a procedure that we named "one shot," which consists of a single dilation of the track with a 25F or 30F Amplatz dilator, compares favorably in terms of efficacy, costs, and length with the other techniques of track dilation, without a significant increase in morbidity. PATIENTS AND METHODS: Seventy-eight consecutive patients who underwent PCNL for stone disease from June 1998 to July 1999 were considered and divided into three groups according to the type of tract dilation used: A (Alken telescoping dilators), B (balloon), or C (one shot). Radiologic exposure, blood loss, and costs were evaluated. RESULTS: The one-shot procedure compared favorably with both of the other dilation techniques without an increase in morbidity and with significant reductions in X-ray exposure and costs. Indeed, significant differences in estimated blood loss were observed between groups B and C and the minor bleeding for group C. CONCLUSION: Our experience indicates that one-shot dilation is feasible in the majority of patients. It is as safe and effective as the technique regarded today as the gold standard but less time consuming and less expensive. These encouraging results should be confirmed by further studies.

Adult↗

PubMed2001

Comparability issues of survival data.

This study examines the level of homogeneity in cancer registration and follow up techniques adopted by each registry, in order to ensure a correct evaluation of the data and of the geographical differences observed within Italy. A quality check was performed on the registration techniques, assuring that they met the international standards and yielded correct data, and on follow up methods. Difficulties concerning the assessment of certain tumours emerged from international debates. Thus, registries were requested to fill in a questionnaire to thoroughly examine differences in the management of tumour cases with difficult biological and clinical assessment (e.g. in situ and urinary bladder tumours). Some discrepancies in registration methods were observed. The most significant problems concern urinary bladder tumours, especially in coding procedures of in situ and uncertain behaviour tumours and the proportion of short-term survivors proportions for some geographical areas. Good quality and comparability indices were generally observed (microscopic verification, follow up management). In conclusions, quality standards in cancer registration appear good and allow for a correct geographical comparability. Some important problems regard only a small number of cancer sites (namely urinary bladder), whose results should be examined with caution.

Female↗

PubMed2001

Coding criteria of bladder cancer: effects on estimating survival.

The aim of this study is to evaluate the consistency between routine methods for coding urinary bladder tumours in eight Italian cancer registries and the European Network of cancer registries (ENCR) criteria. Furthermore, it aims to evaluating the impact of the discordance on survival data. Eight cancer registries took part in the study: Ferrara, Florence, Macerata, Ragusa, Romagna, Sassari, Turin and Varese. The first 100 cases of neoplasm of the urinary bladder incident in the years 1993-1994 were identified from the files of each registry. The original pathology reports were made available. A working group considered eligible to the study 699 cases of microscopically confirmed transitional carcinoma (ICD-O morphology code 812-813). Using the ENCR criteria, each of these was classified according to morphology code (8120 vs. 8130) and behaviour (1/ uncertain, /2 non-invasive, 3/ invasive). Information of tumour behaviour was classified as follows: (i) present, when expressly stated in the original report, (ii) deducible, when not expressly stated but suggested by the pathologist's description, and (iii) absent, when impossible to determine on the basis of the original pathology report. The working group classification of tumour behaviour and the classification of the registry of origin were compared. There was a full concordance in the case of complete agreement on the morphology code, and partial concordance when only the invasive or non-invasive behaviour code was agreed upon. As much as 92.5% cases were microscopically confirmed. Tumour behaviour was expressly stated in the original report of 69.2% cases, not stated but suggested by the pathologist's description in 21.2% cases, and impossible to determine in 9.6%. Agreement between the panel and the registry of origin was complete in 71.2% cases and partial in 12.3% while there was a complete discordance in 16.5% cases. The panel interpreted as non-invasive 111 cases coded as invasive by the registry of origin. Conversely, it was estimated that 24% cases included in incidence data were non-invasive. This article discusses the impact of misclassification on survival data.

Female↗

PubMed2000

Sporadic colorectal adenocarcinomas with high-frequency microsatellite instability.

BACKGROUND: Widespread microsatellite instability (MSI) occurs in nearly 15% of sporadic colorectal cancers. Large bowel carcinomas with high-frequency MSI (MSI-H) (instability at > or = 30% of microsatellite loci) are believed to display distinctive pathologic features and to behave less aggressively than microsatellite-stable (MSS) tumors and carcinomas with low-frequency MSI (MSI-L) (instability at < 30% of microsatellite loci). The aim of the current study was to accurately define the clinicopathologic and biologic features of MSI-H sporadic colorectal carcinomas. METHODS: MSI status was evaluated in 216 large bowel adenocarcinomas using polymerase chain reaction (PCR) and 6 microsatellite markers. Tumors that showed instability with at least two microsatellite markers were classified as MSI-H, whereas the other tumors were classified as MSI-L (instability at one locus) or MSS (no instability). Expression of p53, hMLH1, and hMSH2 gene products was determined by immunohistochemistry, and DNA ploidy pattern was determined by flow cytometry. The prognostic significance of MSI status was assessed by univariate and multivariate survival analyses. RESULTS: The significantly different pathologic features of MSI-H carcinomas were proximal location; large size; mucinous and medullary histotype; poor differentiation; expanding pattern of growth; more frequent Crohn-like conspicuous lymphoid reaction; and low incidence of extramural vein invasion. Most MSI-H tumors were DNA diploid (33 of 40 tumors; 82.5%) and p53 negative (34 of 44 tumors; 77.3%). Conversely, DNA aneuploidy and p53 overexpression were observed in 82.3% (130 of 158 tumors; P < 0.0001) and 54.1% (93 of 172 tumors; P = 0.0002) of MSI-L/MSS tumors, respectively. Loss of hMLH1 or hMSH2 expression was detected in a high fraction of MSI-H carcinomas (86. 0%). Patients with MSI-H tumors showed a better clinical outcome than patients with MSI-L/MSS tumors (P = 0.0017). Furthermore, in multivariate analysis that included conventional clinicopathologic parameters, MSI status, and p53 expression as covariates, MSI status was a significant independent prognostic indicator of disease specific survival. CONCLUSIONS: Assessment of MSI status is an essential step in the genetic characterization of large bowel carcinomas and identifies a subset of tumors with distinct clinical, pathologic, and biologic features.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Changes in HDL-cholesterol and lipoprotein Lp(a) after 6-month treatment with finasteride in males affected by benign prostatic hyperplasia (BPH).

Androgen effects on lipoproteins, mainly high density lipoprotein (HDL), could be exerted by a direct interaction of testosterone (T) or dihydrotestosterone (DHT) with liver androgen receptors. To assess if T needs to be converted into DHT to affect lipid metabolism, 13 patients were studied, affected with benign prostatic hyperplasia (BPH) and treated with an inhibitor of 5 alpha-reductase (finasteride). They were compared with 15 untreated controls. At baseline and after 3 and 6 months of therapy, each patient was evaluated as for lipoprotein and hormone concentrations, as well as for nutritional status. Body composition was assessed by anthropometry and bio-impedance analysis (BIA). Treatment was associated with a significant increase of HDL-cholesterol (HDL-C), mainly HDL3 subclass, and lipoprotein(a) (Lp(a)), as well as a decline of DHT, whereas no significant changes were apparent for T, estradiol (E2), sex hormone binding hormone (SHBG) and body composition indexes. However, no significant associations between DHT and lipid relative changes were apparent at bivariate correlation analysis. This finding was confirmed by comparing patient subsets identified by cluster analysis, according to HDL subclass individual responses. Rather, a slight association with E2 for HDL2 (positive) and HDL3 (negative) was found. In conclusion, finasteride can modify HDL and Lp(a) concentrations. However, by the data, these effects cannot be definitively attributed to the changes in DHT synthesis induced by finasteride, since a direct and non-specific interference of the drug on liver metabolism cannot be excluded.

Aged↗