Post-diagnosis serum 25-hydroxyvitamin D concentrations in women treated for breast cancer participating in a lifestyle trial in Italy.

OBJECTIVE: To report cross-sectionally serum levels of 25-hydroxyvitamin D [25(OH)D] in women living in Italy within 12 months from breast cancer (BC) diagnosis. METHODS: Baseline data were obtained from 394 women diagnosed with primary BC, enrolled from 2016 to 2019 in a lifestyle trial conducted in Italy. Subjects' characteristics were compared between two 25(OH)D concentrations (hypovitaminosis D<20 and ≥20 ng/mL) with the Chi-squared test or Fisher's exact test for small-expected counts. Using multiple logistic regression-adjusted models, we estimated odds ratios (ORs) of hypovitaminosis D with 95% confidence intervals (CIs) in the total sample and in the unsupplemented subgroup. RESULTS: Hypovitaminosis D was found in 39% of all subjects, 60% in unsupplemented subjects, and 10% in supplemented subjects. Increasing ORs of hypovitaminosis D were found with increasing body mass index, 25-30, >30, and ≥35 versus <25 kg/m2 (ORs: 2.50, 4.64, and 5.81, respectively, in the total cohort and ORs: 2.68, 5.38, and 7.08 in the unsupplemented); living in the most southern Italian region (OR 2.50, 95%CI 1.22-5.13); and with hypertriglyceridemia (OR 2.46; 95%CI 1.16-5.22), chemotherapy history (OR 1.86, 95%CI 1.03-3.38), and inversely with anti-estrogenic therapy (OR 0.43, 95%CI 0.24-0.75) in the total sample. CONCLUSIONS: Hypovitaminosis D in women recently diagnosed with BC and participating in a lifestyle trial in Italy was widespread and highest with obesity, hypertriglyceridemia, and chemotherapy use. Considering that hypovitaminosis D is a risk factor for lower efficacy of bone density treatments and possibly BC mortality, our results suggest the need to promptly address and treat vitamin D deficiency.

Menstrual cycle length, serum lipids and lipoproteins in a cohort of Italian Mediterranean women: findings from Progetto ATENA.

BACKGROUND AND AIMS: Clinical studies suggest that menstrual irregularities are associated with metabolic and hormonal abnormalities, insulin resistance and a hyperestrogenic/hyperandrogenic imbalance, that may influence the risk of cardiovascular disease. METHODS AND RESULTS: The association of these abnormalities with the metabolic syndrome suggests that information on lipid patterns at different menstrual cycle length may be of interest in identifying women at higher cardiovascular risk. The association of lipid patterns with menstrual cycle length was evaluated in a cohort of 5062 women participating in the Progetto ATENA Study. Questions were administered to the participants about their cycle lengths at different periods of time over their reproductive life. The period between 20 and 50 years was investigated: normal cycle length was defined as short (30 days). Perimenopausal women were excluded and variables adjusted for age, BMI and menopausal status. In 4434 participants serum triglycerides were found to increase with an increased number of days in the menstrual cycle: 106 mg/dl in the short cycle pattern (21-26 days); 113 mg/dl in the medium cycle pattern (27-29 days); and 116 mg/dl in the long cycle pattern (30-31 days), whereas total and LDL cholesterol were found to be higher and HDL was lower in women with longer cycles, but the difference was not statistically significant. The results were very similar when the same adjusted analysis was restricted to a subgroup of 3823 women with a stable cycle length over the fourth and the fifth decade of life. CONCLUSIONS: These results suggest that cycle length may be a marker of higher cardiovascular risk due to associated metabolic and hormonal patterns.

Impact of false-negative sentinel lymph node biopsy on survival in patients with cutaneous melanoma.

BACKGROUND AND OBJECTIVES: Sentinel lymph node biopsy is widely accepted as standard care in melanoma despite lack of pertinent randomized trials results. A possible pitfall of this procedure is the inaccurate identification of the sentinel lymph node leading to biopsy and analysis of a nonsentinel node. Such a technical failure may yield a different prognosis. The purpose of this study is to analyze the incidence of false negativity and its impact on clinical outcome and to try to understand its causes. METHODS: The Melanoma Data Base at National Cancer Institute of Naples was analyzed comparing results between false-negative and tumor-positive sentinel node patients focusing on overall survival and prognostic factors influencing the clinical outcome. RESULTS: One hundred fifty-one cases were diagnosed to be tumor-positive after sentinel lymph node biopsy and were subjected to complete lymph node dissection. Thirty-four (18.4%)patients with tumor-negative sentinel node subsequently developed lymph node metastases in the basin site of the sentinel procedure. With a median follow-up of 42.8 months the 5-year overall survival was 48.4% and 66.3% for false-negative and tumor-positive group respectively with significant statistical differences (P < .03). CONCLUSIONS: The sensitivity of sentinel lymph node biopsy was 81.6%, and a regional nodal basin recurrence after negative-sentinel node biopsy means a worse prognosis, compared with patients submitted to complete lymph node dissection after a positive sentinel biopsy. The evidence of higher number of tumor-positive nodes after delayed lymphadenectomy in false-negative group compared with tumor-positive sentinel node cases, confirmed the importance of an early staging of lymph nodal involvement. Further data will better clarify the role of prognostic factors to identify cases with a more aggressive biological behavior of the disease.

Age as predictor in patients with cutaneous melanoma submitted to sentinel lymph node biopsy.

AIMS: To analyse the age as prognostic factor exploring the melanoma database at the National Cancer Institute in Naples. METHODS: Three hundred and ninety-nine patients with cutaneous melanoma were treated with sentinel lymph node biopsy from 1996 to 2003 at the National Cancer Institute of Naples. The results were analysed with particular attention to the overall survival among patients younger or older than 50 years of age. RESULTS: No differences were recorded between the younger and older group in terms of the identification rate and incidence of metastases. The analyses of disease-free survival and overall survival showed a significantly more favourable outcome in younger patients. The 5-year overall survival and the 5-year disease free survival were 81.8% vs. 68.0% and 76.3% vs. 59.1% for the younger and older group, respectively. CONCLUSIONS: The results suggest that in the management of cutaneous melanoma, age might be considered as prognostic factor both for disease free survival and overall survival.

Plasma carotenoids as biomarkers of intake of fruits and vegetables: ecological-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC).

OBJECTIVE: The aim of this study was to assess the ability of a single 24-h dietary recall (24HDR) and food questionnaires (FQ) to predict plasma carotenoid levels at the ecological level by assessing the relationship between mean plasma carotenoid levels and mean intake of fruit and vegetables measured by 24HDR and FQ across 16 European regions. DESIGN: A random subsample of 3089 subjects was included, stratified by age and gender. They provided blood samples and dietary information between 1992 and 2000 as part of the European Prospective Investigation into Cancer and Nutrition. RESULTS: Using Spearman's correlation coefficients, the correlations between mean regional 24HDR fruit and vegetable variables and corresponding mean plasma carotenoid levels were generally higher than the correlations using FQ means. The highest correlation was between the 24HDR citrus fruit variable and beta-cryptoxanthin (r = 0.90). For 24HDR, total fruits and vegetables were highly correlated with lutein, zeaxanthin, and beta-cryptoxanthin (r = 0.83-0.87), while vegetables were more closely related with lutein (r = 0.69) and zeaxanthin (r = 0.68), and fruits correlated with zeaxanthin (r = 0.87) and beta-cryptoxanthin (r = 0.84). Root vegetables (r = 0.81) and total carrots (r = 0.71) were well correlated with alpha-carotene. In the multivariate models adjusting for age, body mass index, and season, and using observations of means stratified by sex and region, the association was generally higher for 24HDR compared to FQ. CONCLUSION: Mean regional intakes of fruits and vegetables in several European countries were closely correlated with corresponding mean plasma levels of individual carotenoids. Fruits and vegetables measured by 24HDR were generally better able to predict plasma carotenoids at the ecological level.

Recovery of erection after pelvic urologic surgery: our experience.

The incidence of erectile dysfunction (ED) in patients undergoing pelvic urologic surgery, the efficacy and tolerability of vardenafil-based rehabilitative treatment as first option in these patients, the role of spontaneous erection (SE) as a possible positive predictive factor to erection recovery after such treatment, and the role of second-line therapies in those nonresponders are evaluated. All the patients undergoing pelvic urologic surgery at our Institution between November 2002 and December 2003 were considered. Preoperative erectile function (EF) was evaluated by using the abridged five-item version of the International Index of Erectile Function (IIEF5) questionnaire. Study population was divided into separate groups considering grade of preoperative EF, nerve sparing (NS) surgery and type of procedure (radical prostatectomy, radical cystectomy (RC) or nerve and seminal sparing cystectomy). In total, 86 patients were evaluated. After 6 months, an increase in mean IIEF5 score of 12.9 points was found in those who had undergone a bilateral NSRP after vardenafil therapy, of 8.0 points in those who had undergone unilateral NSRP, of 11.3 in those who had undergone NSRC and of 11.5 in nerve and seminal sparing cistectomies. A better vardenafil response was found in patients with SE+(P<0.001). Among those vardenafil notresponders, 13 were treated by using intracavernous injections, one by vacuum device and three with penile prosthesis implant. In conclusion, in our experience, vardenafil showed to be well tolerated and effective for recovery of EF in patients undergoing pelvic urologic surgery. This drug was particularly effective for those with a normal preoperative EF undergoing an NS procedure. Of course, it should be recognized that the absence of a control group in the study represents an important limitation. However, based on the data from the literature, there is a strong belief that such an approach will lead to an earlier recovery of EF than without rehabilitative treatment.

HLA allele frequency and clinical outcome in Italian patients with cutaneous melanoma.

The current study focuses the analysis on the possible relationship between HLA allele frequency and clinical outcome of melanoma in a population of 382 Italian patients, as compared with 203 ethnically matched controls. In a 3-year follow-up study, results showed significant differences between groups of patients selected according to clinical stage, histology, and progression of the disease. A*01 seems to be correlated with a less aggressive variant of the disease, whereas DRB1*01-DQB1*0501 seems to be associated with metastatic progression of melanoma. Moreover, a negative association with B*13, B*44, as well as with DRB1*04-DQB1*0302 was found. A multivariate logistic regression model showed HLA-DRB1*04 to behave as an independent favorable prognostic marker of melanoma in our population (OR = 2.34, CI = 1.15-4.74).

Sentinel lymph node biopsy in patients with cutaneous melanoma: outcome after 3-year follow-up.

AIMS: The management of patients with cutaneous melanoma in the absence of lymph-node metastases is still controversial. The experience of the National Cancer Institute in Naples was analysed to evaluate the 3-year disease free survival and overall survival for all patients submitted to sentinel node biopsy (SNB). METHODS: Data from 265 sentinel biopsies performed in the last five years were reviewed to determine the effect of the treatment on disease free survival and overall survival stratified the patients for node status and tumour ulceration. RESULTS: Statistical analysis showed a 3-year survival advantage for sentinel node negative patients compared to sentinel node positive cases with a 88.4 and 72.9%, respectively (p < 0.05). CONCLUSIONS: SNB provides an accurate staging of nodal status in patients with melanoma in the absence of clinical evidence of metastases. Longer follow-up and final results from multicenter selective lymphadenectomy (MSLT) are needed to clarify the role of this procedure.

Cooking of meat and fish in Europe--results from the European Prospective Investigation into Cancer and Nutrition (EPIC).

OBJECTIVES: There is epidemiologic evidence that the consumption of fried, grilled or barbecued meat and fish that are well-done or browned may be associated with an increased cancer risk. These high-temperature cooking methods are thought to be surrogates for mutagens and carcinogens produced in meat and fish, eg heterocyclic amines or polycyclic hydrocarbons. Since data on food cooking methods are scarce, the aim of this study was to describe the variation in meat and fish cooking methods in different parts of Europe. DESIGN: Using a standardized 24 h recall from a sub-sample of the EPIC cohort (35 644 persons, 35-75 y old), mean daily intake of meat and fish prepared by different cooking methods and the relative contribution of the cooking methods to the overall cooking of meat and fish was calculated. RESULTS: Whereas frying was more often noted in northern Europe, roasting and stir frying were more often used in the south. Concerning high-temperature cooking methods, their frequency of application varies between 15% in the EPIC cohort of North-Italy and 49% in the cohort of The Netherlands. Average consumption of fried, grilled and barbecued meat and fish ranges from a low of 12 g/day in the centres in southern Spain to a high of 91 g/day in northern Spain. CONCLUSION: High variation in both the kind of meat/fish consumed as well as its cooking methods is observed within EPIC. In order to use this variation for the evaluation of the impact of cooking methods on cancer risk, a questionnaire on meat and fish cooking methods is being developed and could be applied in the whole EPIC cohort.

Patterns of alcohol consumption in 10 European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) project.

OBJECTIVE: The aim of this study was to compare the quantities of alcohol and types of alcoholic beverages consumed, and the timing of consumption, in centres participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). These centres, in 10 European countries, are characterised by widely differing drinking habits and frequencies of alcohol-related diseases. METHODS: We collected a single standardised 24-hour dietary recall per subject from a random sample of the EPIC cohort (36 900 persons initially and 35 955 after exclusion of subjects under 35 and over 74 years of age). This provided detailed information on the distribution of alcohol consumption during the day in relation to main meals, and was used to determine weekly consumption patterns. The crude and adjusted (by age, day of week and season) means of total ethanol consumption and consumption according to type of beverage were stratified by centre and sex. RESULTS: Sex was a strong determinant of drinking patterns in all 10 countries. The highest total alcohol consumption was observed in the Spanish centres (San Sebastian, 41.4 g day-1) for men and in Danish centres (Copenhagen, 20.9 g day-1) for women. The lowest total alcohol intake was in the Swedish centres (Umeå, 10.2 g day-1) in men and in Greek women (3.4 g day-1). Among men, the main contributor to total alcohol intake was wine in Mediterranean countries and beer in the Dutch, German, Swedish and Danish centres. In most centres, the main source of alcohol for women was wine except for Murcia (Spain), where it was beer. Alcohol consumption, particularly by women, increased markedly during the weekend in nearly all centres. The German, Dutch, UK (general population) and Danish centres were characterised by the highest percentages of alcohol consumption outside mealtimes. CONCLUSIONS: The large variation in drinking patterns among the EPIC centres provides an opportunity to better understand the relationship between alcohol and alcohol-related diseases.

XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample of healthy subjects.

DNA repair genes have an important role in protecting individuals from cancer-causing agents. Polymorphisms in several DNA repair genes have been identified and individuals with non-dramatic reductions in the capacity to repair DNA damage are observed in the population, but the impact of specific genetic variants on repair phenotype and cancer risk has not yet been clarified. In 308 healthy Italian individuals belonging to the prospective European project EPIC, we have investigated the relationship between DNA damage, as measured by (32)P-DNA adduct levels, and three genetic polymorphisms in different repair genes: XRCC1-Arg399Gln (exon 10), XRCC3-Thr241Met (exon 7) and XPD-Lys751Gln (exon 23). DNA adduct levels were measured as relative adduct level (RAL) per 10(9) normal nucleotides by DNA (32)P-post-labelling assay in white blood cells from peripheral blood. Genotyping was performed by PCR-RFLP analysis. The XRCC3-241Met variant was significantly associated with higher DNA adduct levels, whereas XRCC1-399Gln and XPD-751Gln were associated with higher DNA adduct levels only in never-smokers. XRCC3-241Met homozygotes had an average DNA adduct level of 11.44 +/- 1.48 (+/-SE) compared with 7.69 +/- 0.88 in Thr/Met heterozygotes and 6.94 +/- 1.11 in Thr/Thr homozygotes (F = 3.206, P = 0.042). Never-smoking XRCC1-399Gln homozygotes had an average DNA adduct level of 15.60 +/- 5.42 compared with 6.16 +/- 0.97 in Gln/Arg heterozygotes and 6.78 +/- 1.10 in Arg/Arg homozygotes (F = 5.237, P = 0.007). A significant odds ratio (3.81, 95% CI 1.02-14.16) to have DNA adduct levels above median value was observed for XPD-751Gln versus XPD-751Lys never-smoking homozygotes after adjustment for several confounders. These data show that all the analysed polymorphisms could result in deficient DNA repair and suggest a need for further investigation into the possible interactions between these polymorphisms, smoking and other risk factors.

Site-specific atherosclerotic plaques in the carotid arteries of middle-aged women from southern Italy: associations with traditional risk factors and oxidation markers.

BACKGROUND AND PURPOSE: Studies on cardiovascular disease have preferentially involved men because of the lower frequency of the disease in preelderly women. The aim of this analysis was to examine, with the use of a standardized ultrasound protocol, a cohort of women to differentiate early atherosclerotic lesions in different carotid segments in relation to traditional (lipoprotein abnormalities, high blood pressure, cigarette smoking) and nontraditional (oxidation markers) cardiovascular risk factors. METHODS: More than 5000 clinically healthy, middle-aged women (n=5062; age range, 30 to 69 years) living in the area of Naples in southern Italy participated in the Progetto Atena, a population-based study on the etiology of cardiovascular disease and cancer in the female population. A subsample of 310 participants underwent high-resolution B-mode ultrasound to assess intima-media thickness of common carotid artery and carotid bifurcation. RESULTS: Early atherosclerotic plaques (intima-media thickness >1.2 mm) were detected within the common carotid arteries in 37 women, in the carotid bifurcations in 77 women, and in both sites in 91 women. After age adjustment, common carotid plaques were found to be associated with higher systolic blood pressure (143 versus 138 mm Hg; P<0.05) and higher body mass index (29 versus 27 kg/m(2); P<0.01), while lesions at the carotid bifurcations were associated with higher LDL cholesterol (4.3 versus 3.8 mmol/L; P<0.01) and with smoking habit. Multivariate odds ratios for the presence of common carotid plaques were related to antibodies against oxidized LDL (odds ratio, 2.72; 95% CI, 1.46 to 5.07), and those for plaques at the bifurcation were related to lipid peroxides (odds ratio, 1.90; 95% CI, 1.04 to 3.47), and both relationships were independent of age, LDL cholesterol concentrations, body mass index, smoking habit, and systolic blood pressure. CONCLUSIONS: In a cohort of clinically healthy, middle-aged women, we found a site-specific association of traditional risk factors and oxidation markers with early atherosclerotic lesions in arterial segments differing in geometry, shear stress, extracellular matrix composition, and cell type populations.

Drainage in thyroid surgery: a prospective randomised clinical study.

Drainage in thyroid surgery is still an area of controversy. We analysed the results of a prospective randomised trial conducted in our institution in order to assess the utility of drainage after thyroid surgery. Sixty patients were entered into the study, thirty of whom were drained after surgery and thirty who received no drainage. The two groups were well matched with regard to most characteristics. There was no difference between the two groups in terms of early or late postoperative complications. We therefore conclude that, in our experience, drainage after uncomplicated thyroid surgery is of no benefit.

Long-term prognostic value of dipyridamole and dobutamine stress echocardiography in patients with known or suspected coronary artery disease.

BACKGROUND: Pharmacological stress echocardiography (PSE) is increasingly used for cardiac risk stratification. Our study was undertaken to assess the long-term prognostic significance of PSE in patients with known or suspected coronary artery disease. METHODS: We studied 622 consecutive patients who underwent PSE with either dobutamine or dipyridamole. Outcome was finally assessed in 448 patients for a mean period of 32.9 months. Death and hard events (death and myocardial infarction) were considered as endpoints. RESULTS: PSE was positive for ischemia in 192 patients (42.9%). During the follow-up, 53 hard events occurred, including 28 deaths and 25 acute non-fatal myocardial infarctions. With multivariate analysis, peak ejection fraction < 40% appeared to be the strongest predictor of cardiac-related deaths and of hard endpoints (chi2 28.4 and 32.0, respectively). Peak wall motion score index revealed a strong predictive value of the same events (chi2 8.6 and 16.3, respectively). An ischemic pattern at PSE predicted a 2.4 higher cardiac mortality rate over a 5-year follow-up (9.4 vs 3.9%, p < 0.01; log rank 5.68), while patients with a peak ejection fraction < 40% had a cardiac-related mortality 4 times higher (16.3 vs 4.1%, p < 0.00001; log rank 21.16). Hard events occurred in 6.7% of patients with a negative test vs 18.8% of patients with a positive test (p < 0.001; log rank 15.8), while hard event rate was 8.4% in patients with a peak ejection fraction > 40% vs 27.5% in patients with a peak ejection fraction < 40% (p < 0.00001; log rank 38.64). CONCLUSIONS: The ischemic response to PSE showed a sustained prognostic value for cardiac events, especially in patients considered at either intermediate or high risk on the basis of recognized clinical risk factors. However, only the evaluation of both descriptors of global left ventricular performance and of the extension of induced ischemia may better help to select patients at higher risk of cardiac death.

Detection of occult melanoma cells in paraffin-embedded histologically negative sentinel lymph nodes using a reverse transcriptase polymerase chain reaction assay.

PURPOSE: Detection of occult metastasis before the development of clinical disease could allow more accurate staging, appropriate follow-up procedures, and adjuvant therapies in patients with malignant melanoma (MM). The sentinel lymph node (SLN) has been proposed as a reliable predictor of metastatic disease in the lymphatic basin draining the primary melanoma. In this study, we screened both paraffin-embedded SLNs and peripheral-blood (PB) samples from MM patients at various stage of disease using a multimarker reverse transcriptase polymerase chain reaction (RT-PCR) assay. The prognostic significance of the presence of PCR-positive markers was also evaluated. PATIENTS AND METHODS: Total RNA was obtained from paraffin-embedded SLN sections and PB samples of 75 MM patients. RT-PCR was performed using tyrosinase and MelanA/MART1 as melanoma-associated markers. Radiolabeled PCR products were analyzed on denaturing polyacrylamide gels. RESULTS: Good sensitivity of the RT-PCR assay on archival tissues was demonstrated after comparison of RT-PCR results on frozen and paraffin-embedded SLNs from 16 MM patients. Significant correlation between the disease stage and marker expression in both PB and SLN samples was observed; the highest value was for patients who were positive for both markers in SLN (P =.006). Progression of disease was significantly associated with the total number of PCR-positive markers in both PB (P =.034) and SLN (P =.001) samples. CONCLUSION: Although sensitivity is lowered by the use of paraffin-embedded specimens, our data indicate that RT-PCR analysis of serial sections from archival SLNs may be helpful in improving detection of occult micrometastases, thus improving staging of patients with melanoma.

Large-scale hormone replacement therapy and life expectancy: results from an international comparison among European and North American populations.

OBJECTIVES: An analysis was performed to determine the risks and benefits of a 10-year hormone replacement therapy regimen that had been applied to all women at 50 years of age in 8 countries. METHODS: Cumulative mortality with and without hormone replacement therapy over 20 years was estimated, with both current and predicted total and disease-specific secular mortality trends and the influence of a generational cohort effect taken into account. RESULTS: In countries with high ischemic heart disease frequency and predictable relative predominance of ischemic heart disease rates over breast cancer rates for the next 20 years, hormone replacement therapy could result in benefits with regard to overall mortality; this advantage decreases in younger-generation cohorts. In countries in which breast cancer mortality predominates over ischemic heart disease in early postmenopause and in which the predictable trends for both diseases reinforce this condition, a negative effect on overall mortality would be observed. In the United States, the effect of large-scale hormone replacement therapy would change over time. CONCLUSIONS: The long-term effect of hormone replacement therapy on life expectancy of postmenopausal women may vary among countries.

Sensitivity and specificity of epiluminescence microscopy: evaluation on a sample of 2731 excised cutaneous pigmented lesions. The Melanoma Cooperative Study.

To evaluate the role of epiluminescence microscopy (ELM) in the differential diagnosis of cutaneous pigmented lesions, and to improve the early diagnosis of cutaneous malignant melanoma (CMM), 15,719 pigmented lesions from 8782 consecutive patients were evaluated using ELM with a hand-held video microscope imaging system (MS 500B Micro-Scopeman, Moritex). Comparison between risk levels as inferred from ELM screening and histology was performed on 2731 surgically excised lesions. ELM sensitivity, specificity, positive and negative predictive values, as well as agreement with histological results for the different subgroups of lesions, were determined. Overall agreement was 87.3% (ranging from 85.1% to 92.2% for melanocytic and non-melanocytic lesions, respectively); sensitivity and specificity were high (values ranging from 87.3% to 96.3% among different subsets of ELM-analysed lesions) and statistically significant (P < 0.0001). ELM screening identified 165 new cases of CMM with a high proportion of lesions (115; 70%) in an early phase of tumour growth (Breslow thickness