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.

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.

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.

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.

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.

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.

Raised plasma fibrinogen concentrations in subjects attending a metabolic ward--relation to family history and vascular risk factors.

We have evaluated plasma fibrinogen levels in 171 subjects attending a metabolic ward. As in the general population, a significant difference in plasma fibrinogen concentrations (p < 0.05) was found between subjects with diabetes mellitus or hypertension and those without. However, fibrinogen was also abnormally high (p < 0.05) when evaluated according to the presence of a family history of ischemic complications of atherosclerosis (p < 0.05). In this setting, fibrinogen correlated with diabetes mellitus or hypertension as well as with familial risk, and the latter interacted with hypertension (p < 0.05) in accounting for plasma fibrinogen. The relationships between certain fibrinogen genotypes and familial risk have then been evaluated. Analysis of a locus (1.3 kb, HAE III digestion) of the promoter region of the B beta fibrinogen gene, identified a polymorphic cutting site. The allele with the alternative restriction site (H1) was associated with mean fibrinogen levels which were 0.1-0.3 g/l lower than those associated with the other allele (H2). This difference was not statistically significant. No obvious association was found between the familial risk and the presence of the H2 allele. We conclude that in a group of subjects from a metabolic ward, a positive family history for ischemic complications of atherosclerosis is consistently associated with high plasma fibrinogen levels. Interaction with hypertension significantly strengthens the association.

Relative validity of multiple telephone versus face-to-face 24-hour dietary recalls.

The relative validity of multiple telephone 24-hour dietary recalls was evaluated in a feasibility study within the framework of a large prospective investigation on the cause of chronic disease in women. Forty-nine women were interviewed four times both face-to-face and by telephone. Comparison of the total number of calories and intake of protein, carbohydrate, total and saturated fats, cholesterol, fiber, sodium, potassium, calcium, vitamin A, and vitamin C as estimated by multiple face-to-face and telephone interviews revealed an acceptable relative validity for the telephone procedure. Analysis of the position variation in the distribution (percent agreement) comparing the two procedures showed that a change in the distribution of none or one quintile occurs in more than 70% of individuals for all nutrients but vitamin C (69.4%), cholesterol (61.2%), and vitamin A (51.4%). Correlation coefficient analysis showed similar results. Adjustment for nutrient densities did not affect the overall results. Multiple 24-hour telephone dietary recalls appear to be a valid alternative to face-to-face interviews in population studies.

Body fat distribution, peripheral indicators of androgenic activity, and blood pressure in women.

This report analyzes the association between blood pressure and three indicators of peripheral androgenic activity (PIAAs): body fat distribution, hirsutism, and sebum production. Furthermore, it analyzes the associations among these PIAAs to understand whether they are indicators of the same androgenic pattern. The study was conducted among 314 healthy women, aged 35-69 years, participating in the baseline examination of the Study of Hormones and Diet in the Etiology of Breast Cancer (ORDET), an Italian cohort study of breast cancer. Body fat distribution was measured as the ratio of waist-to-hip circumference (waist-to-hip ratio). Three hirsutism scores were developed by use of factor analysis after nine areas of androgen-sensitive, pilo-sebaceum units of the body were examined. Sebum production was measured by a sebumeter. Results indicated a positive correlation between the waist-to-hip ratio and the lip hirsutism score (r = 0.157). Conversely, sebum production correlated negatively with both the lip hirsutism score (r = -0.154) and the waist-to-hip ratio (r = -0.153). By use of multiple regression and with adjustment for age and body mass index, the waist-to-hip ratio was found to be positively and significantly related to both diastolic and systolic blood pressure, whereas sebum production was inversely and significantly related to both diastolic and systolic blood pressure. The facial hirsutism score was positively related to systolic blood pressure, while the limb hirsutism score was inversely and significantly related to diastolic blood pressure. Finally, interrelationships among these markers of androgenic activity were found to be weak, suggesting that these markers may be under the influence of local metabolism of the androgenic steroids. Further hormonal analyses are needed to determine whether PIAA measures obtained in epidemiological settings are useful in study of androgenic patterns and blood pressure.

Coffee and serum lipids: findings from the Olivetti Heart Study.

The relationship between coffee consumption and blood lipids was analyzed in a sample of 900 male workers of southern Italy participating in the Olivetti Heart Study. In the univariate analysis, coffee drinkers (n = 856) had higher values for body mass index (P < or = 0.05) and number of cigarettes smoked per day (P < or = 0.001) and lower levels of serum high-density-lipoprotein cholesterol (P < or = 0.05), compared to noncoffee drinkers (n = 44). In addition, coffee consumption (cups/d) was positively related to serum triglyceride levels (r = 0.105, P < or = 0.01) and cigarette smoking (r = 0.491, P < or = 0.01), and was inversely related to age (r = -0.122, P < or = 0.01). After multivariate adjustment, coffee consumption remained significantly related to age, cigarette smoking, and body mass index (data not shown). After stratification for smoking status, a significant positive linear trend between coffee consumption and serum total cholesterol was observed only in smokers. No significant trend was observed for serum triglycerides and high-density-lipoprotein cholesterol with coffee intake according to smoking status. This finding suggests that the relationship between coffee consumption and serum total cholesterol may change with the smoking status.

Does a relationship exist between trends in estrogen receptor levels and breast cancer incidence and mortality?

Estrogen receptor data from 4,049 patients with primary breast cancer treated at the National Cancer Institute of Naples between 1984 and 1996, have been evaluated to analyze temporal trend of this tumor marker. The prevalence rate of estrogen receptor levels falls from >75% in women older than 60 years to <70% in younger patients. The analysis of these data by birth cohort shows a trend very similar to that of breast cancer incidence in Italy, suggesting that the breast cancer appearance could be modulated in different period of life.

Lipoprotein(a) concentrations in non-insulin-dependent diabetes mellitus and borderline hyperglycemia: a population-based study.

The objective of the study was to compare lipoprotein(a) [Lp(a)] concentrations in population-based samples of individuals with non-insulin-dependent diabetes mellitus (NIDDM), borderline hyperglycemia, and normoglycemia. From 2,740 male Italian Telephone Company employees aged 40 to 59 years participating in a health screening, we selected all those with NIDDM (n = 100) plus a random sample of 950 nondiabetic individuals. Diabetes was defined as fasting plasma glucose (FPG) of at least 140 mg/dL or current use of hypoglycemic drugs. Among nondiabetic individuals, 854 were defined as normoglycemic (FPG < 115 mg/dL) and 95 were defined as borderline hyperglycemic (115 < FPG < 140 mg/dL). Lp(a) level was measured on frozen plasma by enzyme-linked immunosorbent assay. Lp(a) concentrations were similar in people with NIDDM, borderline hyperglycemia, and normoglycemia: 11.2 +/- 14, 14.1 +/- 20, and 13.9 +/- 18 mg/dL, respectively (F = 1.03). Accordingly, the proportion of subjects with Lp(a) levels of at least 30 mg/dL was comparable in the three groups (12%, 15%, and 14%; chi 2 = 3.95, P = .41). Results were not confounded by differences in age, body mass index (BMI), waist to hip ratio, plasma lipids, alcohol consumption, physical activity, and use of drugs. Furthermore, within the diabetic group Lp(a) levels were not significantly different for those on diet only versus those on oral agents (10.8 +/- 14.1 v 11.7 +/- 14.7, P = .7) or for people with FPG of at least 180 as compared with people with FPG less than 180 mg/dL (9.9 +/- 12.8 v 11.5 +/- 14.8, P = .5).(ABSTRACT TRUNCATED AT 250 WORDS)

Stiffness of the aortic wall in hypercholesterolemic children.

Arterial stiffness may be an indicator of early vascular changes signaling the development of vascular disease, while hypercholesterolemia is a well-recognized promoter of atherogenesis. It has been shown that hypercholesterolemic children have a thicker intima-media in the carotid artery than children with normal cholesterol. The aim of this study was to assess the stiffness of the abdominal aorta in children with hypercholesterolemia. Noninvasive imaging evaluation of the aorta was performed in 85 outpatient children (age, 3 to 14 years) with and without high cholesterol levels ((and) 247 mg/dL [6.4 mmol/L], respectively). Ultrasound imaging of the abdominal aorta that allowed diameter measurements was available in 67 children. Using an image-processing workstation, the maximum and minimum internal diameter of the aorta was measured, and the following indices of elastic properties of the abdominal aorta were derived: arterial strain, pressure-strain elastic modulus, and stiffness. No statistical difference for aortic strain, stiffness, and elastic modulus was found in normocholesterolemic compared with hypercholesterolemic children. The effect of age on the elastic modulus was different in the two groups: in normal children, the elastic modulus increased linearly with age (y = -0.020+0.003 x age [months], P<.001), while the high-cholesterol group had a weak increase in this parameter with age (y = 0.118+0.0009 x age, P = .051). The slope of the regression equations (elastic modulus vage) was significantly different in the two groups (t = 2.45, P = .017). The behavior of arterial stiffness with respect to age was similar, y = 0.677+0.018 x age (P = .002) in normocholesterolemic children and y = 2.06+0.00198 x age (P = .66) in hypercholesterolemic children. The slope of the regression equations (stiffness v. age) was significantly different in the two groups (t = 2.37, P = .021). The present study demonstrates an influence of hypercholesterolemia on age-related modification in the elastic properties of the aorta. A remodeling of the aortic wall in hypercholesterolemic children (cholesterolemia >247 mg/dL) could explain the different age-dependent increase in aortic elastic modulus and stiffness.

Serum uric acid and hypertension: the Olivetti heart study.

The association between serum uric acid and hypertension was evaluated in a sample of male workers in southern Italy enrolled in the Olivetti Heart Study, an ongoing longitudinal epidemiological investigation on risk factors for coronary heart disease carried out at the Olivetti factory in the suburban area of Naples. Participants were screened at baseline (1975) and at five year (1980) and 12 year (1987) follow-up examinations. The present report focuses on 619 male workers for whom information on coronary heart disease risk factors was available both at baseline and 12 year follow-up examination. At baseline, after excluding hypertensive participants (systolic blood pressure (SBP) > or = 140 mmHg and/or diastolic blood pressure (DBP), > or = 90 mmHg and/or on antihypertensive therapy; n = 72), serum uric acid was positively and significantly related to age, SBP, DBP, body mass index (BMI), serum total cholesterol (CHOL) and serum triglycerides (TG) in 547 normotensive participants. At 12 year follow-up examination, hypertension was defined by SBP > or = 140 mmHg and/or DBP > or = 90 mmHg and/or being on antihypertensive therapy. Multiple logistic regression analysis showed an independent positive association between serum uric acid levels and development of hypertension (RR = 1.23, 95% CI = 1.07-1.39; p = 0.011) after adjustment for age, BMI, CHOL and TG. Furthermore, according to more severe degrees of hypertension (SBP > or = 160 mmHg and/or DBP > or = 95 mmHg and/or being on antihypertensive therapy), the relative risk to develop hypertension was still significant (RR = 1.19; CI = 1.01-1.38; p = 0.051).(ABSTRACT TRUNCATED AT 250 WORDS)

INTERSALT in Italy: findings and community health implications.

In INTERSALT, an international cooperative study on electrolytes and blood pressure, significant associations were found, in the pooled data for 52 centres, between systolic BP and sodium (Na) excretion, body mass index (BMI), high alcohol intake and low potassium (K) excretion. We have assessed the status of the four Italian centres (Mirano, Gubbio, Bassiano, Naples) on these variables. The four centres examined a total of 794 men and women aged 20-59 years. Combined values were similar to overall INTERSALT levels for daily Na excretion (170 mmol) and BMI (25 kg/m2). The Italian centres had slightly higher potassium excretions (57 vs. 55 mmol/day), a higher prevalence of drinkers and a greater average alcohol consumption. Participants were divided into those below or above median levels of Na, K, BMI, and by alcohol intake (below or above 300 ml/week). Both systolic BP and diastolic BP were found to be lower in the more favourable stratum, for each variable. When all four factors were combined, those below median Na excretion and BMI, above median K, and with alcohol intake less than 300 ml/week had age-adjusted systolic BP 7.5 mmHg lower than those with less favourable levels of all four variables. The difference in adjusted diastolic BP was 4.3 mmHg. The data indicate the potential for lower population average BP with improved lifestyles.

Coping and blood pressure.

The relationship between psychological coping strategies and BP was analysed in a group of 158 southern Italian men and women aged 20-59, randomly selected from an epidemiological study on coronary heart disease risk factors. Coping strategies were evaluated by use of a self-administered questionnaire (Jalowiec Coping Scale) listing 40 frequently used strategies. Factor analysis revealed the reported use of 5 different coping strategies. Males, on average, reported seeking less external support than females. In both sexes, increased years of education were associated with increased use of solution-oriented coping strategies and decreased use of resignation and sympathy seeking. After adjustment for age, alcohol use, body mass index, education and smoking, increased use of resignation was associated with lowered BP in both sexes. Emotional coping was inversely related to BP in males, but not in females. The search for external support was associated with a higher BP only in males. These data provide some evidence to suggest that psychological coping modalities are related to blood pressure.

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.

Immunological and clinical effects of intramuscular rIFN alpha-2a and low dose subcutaneous rIL-2 in patients with advanced malignant melanoma.

Fifteen patients with tumour recurrence following radical surgical excision of malignant melanoma were treated with a combination of interferon alpha-2a (rIFN alpha-2a) and interleukin-2 (rIL-2). Immunological monitoring (performed prior to therapy and on days 7, 21, and 28, of each course of treatment) showed significant changes of several parameters after rIFN alpha-2a and rIL-2 administration. A significant increase in cells expressing CD16 (cells bearing Fc receptor), CD25 (cells bearing IL-2 receptor), and CD56 (NK cells, activated lymphocytes), as well in levels of soluble IL-2 receptor, beta 2-microglobulin and neopterin was observed. Immunological changes were closely related to the injection of the biological agent and were more relevant during the first than the second cycle of treatment. rIFN alpha-2a and rIL-2 exerted a clear synergistic activity on the same immunological parameters. No major response was seen with the present approach: four subjects showed rapid progression of decrease during the first month of therapy, while of 11 patients who completed two courses of treatment, only five were considered in stable disease. In conclusion, our results suggest that a combination of rIFN alpha-2a and rIL-2, at dosages and schedules, used in this trial, was well-tolerated and immunologically active, but was clinically ineffective in the management of advanced melanoma.

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.