Early detection of second breast cancers improves prognosis in breast cancer survivors.

BACKGROUND: The impact of early detection of second breast cancers in women who have survived a primary breast cancer is unknown. We examined the prognostic effect of detection of ipsilateral breast relapse (IBR) or contralateral breast cancer (CBC) in the asymptomatic relative to symptomatic phase. PATIENTS AND METHODS: Subjects were women with histology-verified second (invasive or in situ) breast cancer (N = 1044) in a breast centre in Florence (1980-2005). Symptom status, test, tumour stage, and outcomes data were obtained from clinical records and linkage with mortality registry. Disease-specific survival was measured from first cancer diagnosis to avoid lead-time bias. Sensitivity analysis was used to allow for length-time bias. RESULTS: Second cancers (IBR = 455; CBC = 589; median age 60 years) were diagnosed in 699 asymptomatic and 345 symptomatic women (67% versus 3%, P < 0.0001). Mammography was more sensitive than clinical examination (86% versus 57%, P < 0.0001); however, 13.8% of cases were only identified clinically. Asymptomatic cancers were smaller than symptomatic for both IBR (P < 0.001) and CBC (P < 0.001). Early-stage tumours were more frequent in asymptomatic (58.1%) than symptomatic (22.6%) women (P < 0.0001). Fewer women with asymptomatic than symptomatic CBC had node metastases (P = 0.0001). Hazard ratio (HR) for asymptomatic (relative to symptomatic) detection was 0.51 (0.32-0.80) for IBR, 0.53 (0.36-0.78) for CBC, and 0.53 (0.40-0.72) in all subjects (P < 0.0001). Length bias-adjusted HRs ranged from 0.53 to 0.73. CONCLUSION: Detection of second breast cancers in the asymptomatic phase leads to detection of early-stage cancer and improves relative survival by between 27% and 47%.

Severe HDL deficiency due to novel defects in the ABCA1 transporter.

OBJECTIVES: The objective was the identification and functional characterization of mutations in the ABCA1 gene in four patients with severe HDL deficiency. SUBJECTS: Patients were referred to the clinic because of almost complete HDL deficiency. METHODS: The ABCA1 gene was sequenced directly. The analysis of the ABCA1 protein, ABCA1 mRNA and ABCA1-mediated cholesterol efflux was performed in cultured fibroblasts. Intracellular localization of ABCA1 mutants was investigated in transfected HEK293 cells. RESULTS: Two patients were homozygous for mutations in the coding region of the ABCA1 gene, resulting in an amino acid substitution (p.A1046D) and a truncated protein (p.I74YFsX76). The third patient was homozygous for a splice site mutation in intron 35 (c.4773 + 1g>a), resulting in an in-frame deletion of 25 amino acids (del p.D1567_K1591) in ABCA1. These patients had clinical manifestations of accumulation of cholesterol in the reticulo-endothelial system. The fourth patient, with preclinical atherosclerosis, was a compound heterozygote for two missense mutations (p.R587W/p.W1699C). ABCA1-mediated cholesterol efflux was abolished in fibroblasts from patients with p.A1046D and del p.D1567_K1591 mutants and in fibroblasts homozygous for p.R587W. A reduced ABCA1 protein content was observed in these cells, suggesting an increased intracellular degradation. The mutant p.W1699C was largely retained in the endoplasmic reticulum, when expressed in HEK293 cells. CONCLUSIONS: The homozygotes for mutations which abolish ABCA1 function showed overt signs of involvement of the reticulo-endothelial system. This was not the case in the compound heterozygote for missense mutations, suggesting that this patient retains some residual ABCA1 function that reduces cholesterol accumulation in the reticulo-endothelial system.

Second breast cancers in a Tuscan case series: characteristics, prognosis, and predictors of survival.

Little is known about long-term outcomes following a second breast cancer diagnosis. We describe the epidemiology, characteristics and prognosis of second breast cancers in an Italian cohort. We identified women with two breast cancer diagnoses from 24 278 histology records at a Tuscan breast cancer service between 1980 and 2005, and determined their survival status. Disease-specific survival from second diagnosis was examined using Cox regression analyses. Second cancers were identified in 1044 women with a median age of 60 years. In all 455 were ipsilateral relapses and 589 were contralateral cancers. Median time between first and second diagnosis was 63.4 months. The majority of second cancers was small invasive or in situ tumours. Estimated 10-year survival from a second cancer diagnosis was 78%. Survival was poorest when the second cancer was large (HR=2.26) or node-positive (HR=3.43), when the time between the two diagnoses was <5 years (HR=1.45), or when the diagnosis was in an earlier epoch (HR=2.20). Second tumours were more likely to be large or node-positive if the first breast cancer had these features. Prognosis following a second breast cancer in this cohort was generally good. However, large or node-positive second tumours, and shorter intervals between diagnoses were indicators of poorer survival.

Hepatocellular carcinoma complicating primary sclerosing cholangitis in Crohn's disease. A case report.

The prevalence of primary sclerosing cholangitis (PSC) in Crohn's disease (CD) patients is up to 8.5%. Although cholangiocarcinoma may complicate long-standing PSC in one third of the cases if follow-up is extended long enough, hepatocellular carcinoma (HCC) is a rare complication of PSC. The concomitant presence of PSC, HCC and CD have been reported sporadically. We discuss here a case of association of these three conditions.

Efficacy and safety of oral beclomethasone dipropionate for ileal or ileal-right colon Crohn's disease of mild-to-moderate activity or in remission: Retrospective study.

Although conventional glucocorticosteroids are the main treatments for active Crohn's disease, several problems are associated with steroid dependence and steroid-related adverse events. To assess the efficacy and safety of oral beclomethasone dipropionate (BDP) coated tablets in adults with mild-to-moderate Crohn's disease. Thirty-four patients (age 18-70years) with a diagnosis of Crohn's disease confirmed by conventional criteria (barium enema, clinical criteria, colonoscopy, histology) were retrospectively evaluated in the study. All subjects received a treatment schedule with BDP 5-10mg/day for 24weeks. BDP significantly (p=0.005) reduced mean Crohn's Disease Activity Index (CDAI) score from 169.6 at baseline to 123.2 after 24weeks. Clinical success was evident at 24weeks in 66.7% of patients with initial active disease, and remission was maintained at week 24 in 93.8% of patients with remission at baseline. Overall, female non-smokers had the best response to treatment. BDP was well tolerated and the only adverse events observed were nausea (n=1), facial erythema (n=1) and one patient with raised fasting blood glucose level. These results clearly suggest that oral BDP coated tablets are effective and safe for treatment of mild-to-moderate Crohn's disease of ileal or ileal-right colonic localisation.

Assessment of liver fibrosis in the clinical setting: something is changing?

Clinical management of compensated chronic liver diseases (CLD) requires precise definition of the stage of liver fibrosis which is the key histologic predictor of progression to cirrhosis. Several methods are used to assess liver fibrosis. Among those, percutaneous liver biopsy is still the gold standard. However, the recent introduction of liver imaging techniques, the rising of statistical tests able to classify CLD noninvasively, and a reconsideration of its potential complications, have contributed to an audit of the evolving role of liver biopsy. At present, there is an increasing interest for noninvasive approaches to evaluate the stage of liver fibrosis in the clinical work-up of patients with CLD. Transient elastography (FibroScan) is a new, noninvasive method to assess liver stiffness and, consequently, the degree of liver fibrosis. Since its use in the clinical setting is of great interest, further studies should define the exact role of this procedure.

[Gastroenterology outpatient clinic of the Molinette Hospital (Turin, Italy): the 2003-2006 report]. / Poliambulatori specialistici di gastroenterologia: l'esperienza 2003-2006 dell'Ospedale Molinette di Torino.

AIM: Given the demographic shifts and needs of cost rationalization, it is of high priority to organize health care on the basis of ambulatory outpatients models. The aim of this study was to examine activity at the gastro-hepatology outpatients clinic of the Molinette Hospital. In this facility, the management is based on a work team organization that follows cohorts of patients with specific pathologies. METHODS: All services, consultations and urea breath test (UBT) for the diagnosis of Helicobacter pylori infection, carried out from January 2003 to December 2006, were extrapolated from the computerized system. Consultations were divided into first examination and controls. Furthermore, the destination of the patients after each consultation was considered. RESULTS: During the year 2003, 8 842 consultations and 4 071 UBT were carried out, in the year 2004, 11 342 consultations and 2 409 UBT, in the year 2005, 12 474 consultations and 2 510 UBT, in the year 2006, 12 249 consultations and 2 357 UBT. No further specialistic management was required for 25% of patients, while 2% had been hospitalized in the bed unit, 3% in the short hospitalization unit or the day-hospital. The remaining 70% were included in work teams or monitored thereafter. The comparison with consultations from 1994 shows an increase due to both first examination (+300%) and controls (+83%). CONCLUSIONS: The burden of the requests from the population and primary care structures addressed to the outpatients clinic of gastro-hepatology is relevant. The activity of this facility leads to a low rate of hospitalization as well as of cost reduction.

Minority report - false negative breast assessment in women recalled for suspicious screening mammography: imaging and pathological features, and associated delay in diagnosis.

AIM: We studied imaging, pathology and diagnostic aspects of false negative assessment (FNA) in women recalled for suspicious screening mammography. METHOD: Subjects were women aged 50-69 years undergoing biennial screening mammography within the Florence District screening programme from January 1992-December 2001 (339,953 consecutive screens). We identified all cancers occurring in women recalled to assessment and ascertained, and reviewed, all cases considered as negative on assessment and subsequently diagnosed with breast cancer. We compared imaging features, tumour histology and stage, and diagnostic testing on assessment for all women with cancer, and presentation and length of delay in women falsely negative on assessment. RESULTS: Eleven thousand six hundred and twenty four women were recalled to diagnostic assessment (recall rate = 3.4%) predominantly for suspicious mammography (9,216 positive screens). Breast cancer was missed in 57 cases: a FNA rate of 0.50% (0.37-0.62%) and comprising 4.1% (3.0-5.1%) of cancers occurring in women recalled after a positive screen. Two types of abnormalities were significantly more frequent in FNA cases than cancers detected at assessment: mass with regular borders (21.1 vs. 5.6%, p = 10(-5)), and asymmetrical density (22.8 vs. 5.4%, p = 10(-5)). On review 56% of FNAs were benign or probably benign BI-RADS categories. FNA occurred in 1.4% of early recalls and in 0.4% of initial assessment (p=0.0001). Significantly fewer tests were performed when assessing missed cancers than detected cancers with the most significant difference noted for FNAC (29.8 vs. 96.0%, p=10(-6)); mammography as the only evaluation on assessment was more frequent in missed cancers (31.5% vs 0.2%, p = 10(-6)). The 57 missed cases were subsequently diagnosed at early recall (2 cases), next biennial screen (11 cases), or as interval breast cancers (44 cases) with a mean delay in diagnosis of 628 days. Tumour histology, size and nodal status did not significantly differ between cancers missed and cancers diagnosed on assessment. CONCLUSION: False negatives on assessment represent a minority group in whom screening has failed. They might be reduced by adopting a more intensive diagnostic approach to assessment. Although there was no evidence of a worse prognosis in cancers missed at assessment, the delay in diagnosis is substantial and may impact long-term outcomes.

[Non-invasive diagnosis of Helicobacter pylori infection in the 2006 clinical practice]. / La diagnosi "non invasiva" dell'infezione da Helicobacter pylori nella pratica clinica del 2006.

At present, 2 approaches are used to detect Helicobacter pylori (H. pylori): invasive, if based on biopsies taken during endoscopy, and non-invasive, if they do not rely on endoscopic approach. A 3rd option is offered by the string test, that employs an invasive non-endoscopic strategy. The present review attempts to update on the diagnostic non-invasive approaches to patients in the clinical setting. Non-invasive tests include urea breath test (UBT), antigen stool assay, serology, and ''doctor's tests''. The choice of the methods depends on the situation, for example, the clinical circumstances, the diagnostic accuracy, the costs of the testing strategy, and the availability of the tests in the respective area. According to European guidelines, UBT and antigen stool assay are recommended in patients without alarm symptoms or under 45 years of age, at low risk of malignancy in the test and treat strategy. Confirmation of H. pylori eradication following treatment should be tested by UBT; the stool antigen assay is the alternative if the former is not available.

Second reading of screening mammograms increases cancer detection and recall rates. Results in the Florence screening programme.

OBJECTIVE: To assess double reading effectiveness in mammography screening. DESIGN: Retrospective study of 177,631 consecutive mammograms double read during 1998-2003. SETTING: The Florence screening programme, involving 11 trained radiologists. Abnormalities reported by at least one reader prompted assessment. RESULTS: The referral rate was 2.89% for the first reader, 3.15% for the second reader, and 3.59% for either reader. Of 713 total cancers detected, 43 were suspected only by the second reader (6.4% relative, 0.024% increase in absolute detection rate) and had a lower stage compared to the first reader (pTis-pT1b = 65.7 versus 52.0%): 41 were reviewed and classified (error type) as "minimal sign" in six, and "screening error" in 35 cases, or as BI-RADS 3 in one, 4a in 20, 4b in 13, and 4c in three cases. The second reading cost was 2.70 per woman examined, or 11,168 per additional cancer detected (versus 11,585 at a single reading). DISCUSSION: Second reading is effective in detecting a limited number of additional cancer cases. Tumour stage (one-third over 1 cm in diameter) and review findings (high rate of "screening errors" and BI-RADS R4b-c categories) suggest that second reading detects small "difficult cases" as well as larger cancers missed due to fatigue or loss of attention. Second reading reduces screening specificity to a minor extent, and since cancer detection at second reading seems cost-effective the procedure is recommendable in routine practice.

Autoimmune manifestations during interferon therapy in patients with chronic hepatitis C: the hepatologist's view.

In face of numerous benefits induced by therapy based on interferon (IFN) associated with ribavirin for the treatment of chronic hepatitis C, there is an increasing concern regarding its tolerance, which can, in some cases, reduce the quality of life as well as compliance of patients. Among the less common side effects, there are the autoimmune ones which can be globally divided into appearance or increase in titres of auto-antibodies and/or manifestation of overt autoimmune pathologies. Whereas the former may concern more than 50% of treated subjects, the latter is reported in only 1-2% of patients under therapy. Thyroid dysfunction represents the well-studied autoimmune disorder. The presence of pre-existing anti-thyroid antibodies and being of female sex, constitute relevant risk factors for the development of a disease involving this gland. Often the treatment of thyropathy must be continuous in spite of IFN discontinuation because the disturbance usually does not abate with stopping antiviral therapy. Some observations have pointed out to the fact that IFN can lead to the development of insulin-dependent diabetes mellitus. Sometimes, during, as well as after IFN treatment, the appearance of anti-islet cell antibodies has been shown, but its interrelationship with the development of disease is uncertain. While being treated with IFN for chronic hepatitis C, the finding of non-organ specific antibodies at baseline can increase the likelihood of the development of autoimmune hepatitis. However, their presence does not constitute an absolute contraindication to the treatment, except in case of high titre. Other disorders, such as a lupus erythematosus-like syndrome, haemolytic anaemia, and immune-mediated thrombocytopenia have been reported. In conclusion, although the presence of auto-antibodies is considered to be an epiphenomenon without pathogenic significance in most patients suffering from chronic hepatitis C, it poses a problem when they need to be treated with IFN. This antiviral drug can induce or exacerbate a multitude of autoimmune-related disorders, however, clinically overt immune-mediated diseases are rare and affect a subset of subjects who have an underlying autoimmune diathesis.

Florence-Sydney Breast Biopsy Study: sensitivity of ultrasound-guided versus freehand fine needle biopsy of palpable breast cancer.

BACKGROUND: Fine needle aspiration biopsy (FNAB) is widely used in the diagnosis of breast cancer. It is unknown whether, for palpable cancers, ultrasound-guided FNAB is more accurate than freehand FNAB, and practice varies between physicians, services and countries. METHODS: From consecutive women attending a major cancer centre in Florence, we prospectively recruited subjects who had a definitely palpable lump which was solid on ultrasound and suspicious of malignancy (n = 102). All subjects were investigated using both ultrasound-guided and freehand FNAB (one aspirate with each method). Radiologists skilled in both sampling techniques performed all clinical examinations and aspirations, and for each subject the same radiologist obtained both FNAB samples. Sequence of aspiration method was randomised. Cytological interpretation was blinded to method of sampling. Comparative sensitivity (and insufficiency) for FNAB using the two methods was calculated in all cancers (n = 97). RESULTS: Ultrasound-guided FNAB resulted in 13.6% (5-22%) less insufficient aspirates than freehand FNAB (chi2 = 7.58; p = 0.006). When insufficient aspirates are included and considered as negative, ultrasound-guided FNAB has a 14.6% (5.8-23%) or a 16.5% (7.6-25.4%) significantly better sensitivity than freehand FNAB (for cytology 3-5 positive or cytology 4-5 positive respectively). When insufficient aspirates are excluded from the analysis, ultrasound-guided FNAB has a 1.4% (-1.2 to 3.9%) or a 2.6% (-2.5 to 7.8%) higher sensitivity than freehand FNAB (for cytology 3-5 positive or cytology 4-5 positive respectively) but this difference in the sensitivity of the two methods is not statistically significant. CONCLUSION: Our data suggest that ultrasound-guided FNAB has better sensitivity than freehand FNAB in palpable breast cancer, which is predominantly an effect of a significant reduction in insufficient aspirates, but in part an effect of 'upgrading' cytological classification of cancers.

Laboratory evaluation of the patient with liver disease.

Because the liver performs multiple functions, no single laboratory test or battery of tests is sufficient to provide a complete estimate of the function of the liver in every clinical situation. A broad array of biochemical tests are used to assess the many functions of the liver and to evaluate patients with suspected or established liver disease. These tests are referred to collectively as "liver function tests" (LFTs). LFTs are used to screen people for the presence of liver disease, suggest the underlying cause, estimate the severity, assess prognosis, and monitor the efficacy of therapy. Abnormal LFTs may be the first indication of sub clinical liver disease and may thereby guide further diagnostic evaluation. After the existence of hepatic dysfunction is recognized, the specific pattern of liver test abnormalities may suggest the category of the underlying liver disease, such hepatitis, biliary obstructions, or infiltrative liver disease. The value of screening healthy, asymptomatic persons for liver disease with the use of LFTs is controversial and may not be cost-effective. If screening is performed a panel of tests (e.g., AST, alkaline phosphatase, bilirubin, albumin) is preferable to using a single test because of superior sensitivity and specificity for liver disease and lower cost than the sum of individually performed tests.

Analysis of PSA velocity in 1666 healthy subjects undergoing total PSA determination at two consecutive screening rounds.

The study purpose was to assess PSA velocity (PSAV) in healthy subjects in order to establish a reliable cutoff for the differential diagnosis of prostate cancer in a screening setting. We studied a series of 1666 healthy men aged 55 to 74 years undergoing two total PSA determinations at a four-year interval within a population-based randomized screening trial at the Centro per lo Studio e la Prevenzione Oncologica of Florence. First and second screening round PSA assays (PSA1 and PSA2) were carried out with the same method and by the same laboratory. PSAV (PSA1-PSA2/year) was determined in non-cancer subjects in the overall series or in specific age and PSA subgroups, and in subjects with cancer detected at the second screening round. Average PSAV in 1648 non-cancer subjects was 0.07 ng/mL/year (range -2.18+5.99, 95% CI 0.05-0.09); at least one third of subjects showed a decrease in PSA (negative PSAV), mostly of limited magnitude and in the low PSA range. Average PSAV in the 18 cancer patients was 1.16 ng/mL/year (range 0.10-5.6, 95% CI 0.56-1.77), which is significantly higher (p<0.01) than in non-cancer subjects. None of the cancer patients showed a PSA decrease over time. Whatever cutoff was taken for PSAV, its power to discriminate cancer was limited: in particular the previously used PSAV cutoff of 0.75 ng/mL/year would have included only 42 of the 1648 non-cancer subjects (specificity 97.5%) but excluded eight of the 18 cancer patients (sensitivity 55.5%). At best, with the adopted screening protocol PSAV (cutoff 0.10 ng/mL/year) could have spared 27.9% of non-cancer subjects with PSA > or =2.5 ng/mL further diagnostic assessment and 22.7% of non-cancer subjects with PSA > or =4 ng/mL random sextant biopsy, while missing no cancers. This study provides a reliable estimate of PSAV based on a large unbiased population sample. PSAV is widely variable over time, particularly at low PSA values. PSAV might be of value as an indicator for diagnostic assessment and random sextant biopsy in a screening setting.

Transperineal sonography guided biopsy of the prostate: critical review of 1107 cases.

PURPOSE: To assess the predictive value for a positive biopsy of different indicators (rectal examination, transrectal ultrasonography, total PSA, PSA density). MATERIAL AND METHODS: Positive predictive value was assessed on 1107 consecutive US-guided transperineal biopsies performed from 1991 to 2001 (cancer=344, dysplasia (PIN)=64, atypical hyperplasia=4, benign hyperplasia=686, inadequate=9) with univariate and multivariate analysis. RESULTS: Increasing age (chi square for trend 52.2, p <0.001), positive rectal examination (chi square 233, df=1, p<0.001) or ultrasonography (chi square 191, df=1, p<0.001), total PSA (chi square for trend 68.9, p<0.001) and PSA density (cutoff 0.15, chi square 104, df=1, p<0.001; cutoff 0.20, chi square 104, df=1, p<0,001) were all significantly associated to the likelihood of a positive biopsy outcome. Multivariate analysis stresses the independent role of Psa density over total PSA. If the parameters studied had determined the biopsy, spared benign biopsies [positive rectal examination=505 (66%), positive ultrasonography=467 (61%), PSA>4=124 (16%), PSA>10=159 (74%), PSA density >0,15=426 (62%), PSA density >0.20=517 (75%)] would not have justified the amount of delayed cancer biopsies [positive rectal examination=103 (29%), positive ultrasonography=55 (15%), PSA>4=42 (12%), PSA>10=569 (46%), PSA density >0,15=73 (25%), PSA density >0,20=107 (37%)]. CONCLUSIONS: The parameters currently available prior to biopsy, if used alone, allow no reliable prediction of biopsy outcome. Positive predictive value, particularly for PSA density, allows a better evaluation of biopsy indication, particularly for random sextant biopsies in the 4-10 ng/ml PSA range, which are frequently negative.

Monitoring interval cancers in mammographic screening: the Florence District programme experience.

The aim of the present study was to monitor the occurrence of interval (breast) cancers (IC) as an interim outcome measure of quality assurance in the mammographic screening programme of the District of Florence. IC were identified by linking breast screening data with registrations of breast cancers from the Tuscany Tumour Registry. The main outcome measures were the numbers, rates, and the proportionate incidence of IC. Overall, 90 invasive IC were observed among women who attended the breast screening programme in the District of Florence from 1 January 1985 to 31 December 1993, respectively, 23, 50, on 17 cases, at 1, 2, and 3 years after the last negative screening test. Expressed as a proportion of underlying incidence, the figures are 16, 44, and 46%. As to risk factors for IC, mammographic density was the most important one in the present survey, whereas no effect of age emerges from the present study.

Decreasing eradicaton rate of Helicobacter pylori infection with metronidazole-based triple therapy. A randomised study.

BACKGROUND: Helicobacter pylori (H. pylori) infection plays an important role in the pathogenesis of duodenal ulcer (DU) disease. Low DU recurrences and reinfection rates were universally described, when treatment was effective. It has been suggested that short-term triple therapy, comprising a proton pump inhibitor plus two antibiotics (clarithromycin, amoxicillin or a nitroimidazole), should be used as first choice in treating H. pylori infection. Nevertheless, conflicting results have been reported on using these treatment regimens in different countries, due to the resistance of H. pylori against one or more antibiotics. Our aim was to compare the efficacy, for H. pylori eradication, of 1-week triple therapy versus 10 and 14-day triple schedules, in patients with a history of recurrent DU. METHODS: A total of 159 patients (85 males, mean age 59.2+/-3.2 years) was randomly treated with a triple therapy including a standard dose of omeprazole twice daily, amoxicillin 1 g twice daily and metronidazole 500 mg twice daily. Fifty-three patients received 1-week triple therapy (Group I), 53 subjects were treated with 10-day triple therapy (Group II) and 53 others with 14-day triple therapy (Group III). H. pylori infection at entry and eradication, at least 4 weeks after therapy had ended, was assessed by 13C urea breath test and histology on biopsies from the antrum and the corpus. RESULTS: Of the 159 subjects randomised into the study, 6 (3 in group II and 3 in group III) were excluded from the per protocol (PP) analysis because of discontinuations. At the end of the course of treatment, the overall H. pylori eradication rate in the intention-to-treat analysis, was 73.5% (39/53) in group I, 71.6% (38/53) in group II and 73.5% (39/53) in group III, without any statistically significant difference. Moreover, the PP analysis also showed no statistical differences, with an eradication rate of 73.5% (39/53) in group I, 76% (38/50) in group II and 78% (39/50) in group III. The reported frequency of side-effects was evenly distributed between the groups, but 6 patients (3.7%) stopped because of adverse events only in groups II and III. CONCLUSIONS: The present study shows that there is no significant difference between the three regimens although the 14-day triple therapy shows a slightly higher H. pylori eradication rate. There is a strong need, in our region, to put forward surveillance programmes to monitor the prevalence of local resistant strains and to guide treatment on the basis of resistance patterns.

Predicting prostate biopsy outcome by findings at digital rectal examination, transrectal ultrasonography, PSA, PSA density and free-to-total PSA ratio in a population-based screening setting.

The study offers a retrospective analysis of the positive predictive value (PPV) of several variables, i.e. digital rectal examination (DRE), transrectal ultrasonography (TRUS), PSA value, PSA density (PSAD), and free/total PSA ratio (F/T), for the histologic outcome of 179 prostate biopsies performed within a population-based screening trial. The ratio of spared benign biopsies to missed cancers (SBB/MC) if biopsy results had been decided on the basis of single variables was also evaluated. PPV was 82.9% for DRE, 56.3% for TRUS, 26.6% for PSA (cutoff > or =4 ng/mL), 47.4% for PSA (cutoff > or =10 ng/mL), 42.0% for PSAD (cutoff 0.15), 59.2% for PSAD (cutoff 0.20), 34.9% for F/T (cutoff 0.20) and 40.0% for F/T (cutoff 0.15). SBB/MC was 121/23 for DRE, 96/12 for TRUS, 11/10 for PSA (cutoff > or =4 ng/mL), 107/34 for PSA (cutoff > or =10 ng/mL), 87/23 for PSAD (cutoff 0.15), 109/26 for PSAD (cutoff 0.20), 45/8 for F/T (cutoff 0.20) and 70/14 for F/T (cutoff 0.15). Multivariate analysis of the association with biopsy outcome showed the highest odds ratio for TRUS (13.24, 95% CI=4.4-30.7), and considerably lower values for DRE (4.17, 95% CI=2.0-8-9), PSAD (cutoff 0.20: 3.24, 95% CI=-1.8-5.7) and F/T (cutoff <0.15: 3.16, 95% CI=1.7-1.8). None of the possible variable combinations was clinically useful: the highest PPV (83.3%) was obtained with a combination of suspicious DRE/TRUS, PSAD >0.20 and F/T <0.15, which nevertheless missed 20 of 52 cancers.

Interferon and amantadine in combination as initial treatment for chronic hepatitis C patients.

BACKGROUND/AIMS: To evaluate the efficacy and tolerance of amantadine in combination with interferon in the treatment of chronic hepatitis C. METHODS: Multi-centre trial including 180 chronic hepatitis C patients without cirrhosis, randomly enrolled to receive interferon 6 MU every other day for 6 months followed by 3 MU for further 6 months (group A, 90 patients), or the same schedule plus amantadine 200 mg/day (group B, 90 patients). Primary end-point was a sustained virological and biochemical response, secondary end-points were on-treatment (third month) and end-of-treatment response rates. RESULTS: The two groups had similar demographic, biochemical and virological characteristics. A sustained response after 6 months follow-up was observed in 17% of group A and 24% of group B patients (P not significant), an end-of-treatment response was observed in 37% in group A and 47% in group B (P not significant), an on-treatment response was observed in 46% in group A and 61% in group B patients (P < 0.05). No major side effects due to amantadine administration were observed. CONCLUSIONS: Adding amantadine to interferon did not improve the sustained treatment efficacy. However, the rate of early response at the third month of therapy was significantly higher in the combination therapy group.

[Impact of replacement hormone therapy in menopause on breast radiologic density and possible complications of mammography in the assessment of breast masses]. / Impatto della terapia ormonale sostitutiva in menopausa sulla densità radiologica della mammella e possibili implicazioni della mammografia nelle indagini di massa.

PURPOSE: To analyse the association of hormone replacement therapy (HRT) and radiological density, defined as the fraction of breast volume occupied by fibroglandular opacity. MATERIAL AND METHODS: We considered 678 postmenopausal women, consecutively undergoing mammography within an organized screening program, 188 (27.7%) of whom were receiving HRT. Attribution of radiological density was performed prospectively and blind as to HRT status. RESULTS: Both radiological density (p = 0.12) and exposure to HRT (p < 0.001) were found to correlate with age (younger women are more likely to use HRT and to have denser breasts, even without HRT) so the analysis of the correlation between HRT and radiological density was adjusted for the possible confounding effect of age. After stratification by age group, univariate analysis showed a significant correlation between HRT and radiological density (density = > 50%: HRT+ = 34.0%, HRT- = 17.6%: F-value 18.86, df = 1, p < 0.001). Also the duration of HRT was significantly associated to radiological density (Pearson coeff. = 0.12: p = 0.0011). Multivariate analysis adjusting for the confounding effect of age showed an increased risk of dense breast (17% or 7% for a radiological density > 25% or > 50%, respectively) in HRT users with respect to non users. DISCUSSION: The study design, the adoption of a classification of breast density less exposed to intraobserver variability and multivariate analysis of a large series, allows a reliable evaluation of the association of HRT to breast density. As no threshold value is known for the masking effect of density on breast cancer, the negative effect of HRT on screening sensitivity cannot be accurately quantified. CONCLUSIONS: This study confirms the effect of HRT on radiological density in postmenopausal women, suggesting a possible reduction of screening sensitivity and efficacy. Such a hypothesis still needs validation by means of a prospective analysis of the correlation between HRT and the frequency of interval cancer occurrence (the best indicator of sensitivity).