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Biomedical subjects

A Micheli

Publications and source records attributed to A Micheli.

At least 55 records · Page 3Linked to original sources

Quantitative electroencephalography in amyotrophic lateral sclerosis.

OBJECTIVES: The authors evaluated quantitative EEG (QEEG) in patients with amyotrophic lateral sclerosis (ALS), in order to see if the confined cortical degeneration found in anatomical and functional examinations of central (rolandic) regions could give rise to abnormalities of cortical electrical activity. MATERIAL AND METHODS: Eighteen patients with ALS were compared with 14 control subjects comparable for age and sex. The QEEG analysis was blind to the clinical data. Frequency analysis of 30 EEG epochs, each of 2.6 s duration, was performed. RESULTS: QEEG in ALS patients showed a significant well-localized decrease of alpha activity only in the central regions, while theta and delta relative power did not show any difference from controls. CONCLUSION: We suggest that QEEG is able to show evidence of subtle EEG changes probably due to loss of cells in the somatomotor cortex selectively affecting the generator sites.

Adult↗

Conservative surgery and radiotherapy in early stage breast cancer: a comparison between tumourectomy and quadrantectomy.

BACKGROUND AND PURPOSE: This study analyses and compares the results of local regional control, distant metastases and survival in two series of patients irradiated from 1986 to 1992 in our radiation oncology centre following quadrantectomy or tumourectomy for early stage breast cancer. MATERIALS AND METHODS: The quadrantectomy group consisted of 152 women, 109 (72%) with T1 and 43 (28%) with T2 tumours. Axillary nodes in this group were positive in 51 (33%) patients. The tumourectomy group included 123 women, 71 (58%) with T1 and 52 (42%) with T2 tumours. Positive axillary nodes were found in 56 (46%) of these patients. All quadrantectomy and tumourectomy patients received a dose of 50 Gy in 5 weeks to the whole breast, followed by a 10-16 Gy electron boost. Node positive patients in the tumourectomy group also received 50 Gy to the axillary apex and supraclavicular region. In both surgical groups, node positive premenopausal and postmenopausal patients received adjuvant CMF or tamoxifen therapy, respectively. RESULTS: After a median follow-up of 58 months, 89% of women in the tumourectomy group and 87% in the quadrantectomy group were alive and 80 and 73%, respectively, were free of disease. Breast and nodal failures were detected in 4.9 and 0.8% of cases, respectively, in the tumourectomy group, as compared to 5.9 and 3.3% of cases, respectively, in the quadrantectomy group. Distant relapses were observed in 16 and 18% of patients in the former and latter groups, respectively. Actuarial overall and disease-free survival was similar in the two series, with 5-year rates of 90 and 72%, respectively, in the tumourectomy group, and of 91 and 78%, respectively, in the quadrantectomy group. The differences in survival are not statistically different. CONCLUSIONS: Our findings show that tumourectomy and quadrantectomy, followed by adequate radiotherapy, provide comparable results in terms of local-regional control and survival.

Adult↗

The prognostic role of gender in survival of adult cancer patients. EUROCARE Working Group.

Many observations indicate that women have a much longer expectancy of life than men. Some population-based studies on cancer patients support the idea of the role of gender in predicting survival. However, the data are somewhat contrasting and inconclusive. The purpose of this paper was to evaluate the prognostic role of gender for cancer patients, making use of the large set of survival data made available by the EUROCARE II project for the period 1985-1989. By applying a multivariate approach the major confounders such as age, geographical area and cancer site were considered in analysing survival data on more than 1 million cancer cases collected by 45 population-based cancer registries in 17 European countries. The results were consistent with the general observation that in the industrialised countries women tend to survive longer than men. The multivariate analysis showed better survival from cancer in women than in men, estimated as an overall 2% lower relative risk of dying. The female advantage was particularly evident in young cases, reduced in patients in middle age groups and in the oldest patients completely reversed so that at this age men had the better prognosis. Longer survival for women was not present immediately after diagnosis, but the major advantage was seen after 3 years of follow-up. The risk of death for women was significantly lower for cancer of the head and neck, oesophagus, stomach, liver and pancreas. For bladder cancer, the risk of death was significantly greater for women. These results can be explained by gender differences in sub-site distributions (head and neck and stomach) and by the differences in the stage at diagnosis (presumably bladder). However, the consistency of the data, evident only when a vast set of data is analysed, suggest that women may be intrinsically more robust than men in coping with cancer.

Adolescent↗

Radiotherapy with or without androgen deprivation in the treatment of localized adenocarcinoma of the prostate.

This study analyzes the results of disease relapse and survival in two series of patients treated between 1974 and 1991 with definitive irradiation, with or without early androgen deprivation, for carcinoma of the prostate localized to the pelvis. All 264 patients were irradiated to the prostate and pelvic lymph nodes with a dose of 50 to 54 Gy in 25 to 27 fractions, followed by a 16- to 20-Gy boost in 8 to 10 fractions to the prostate and periprostatic region. Ninety percent of patients received a total dose to the prostate (pelvis + boost) of 70 Gy. Ninety-nine of the 264 patients underwent early androgen deprivation. The endocrine manipulation program was initiated 0 to 9 months before the beginning of the radiotherapy course and was continued for 2 or more years or until disease progression. All patients who relapsed after radiotherapy alone received late hormonal manipulation. After a median follow-up of 100 months, no difference in the incidence of local and distant failure rate and cancer-specific mortality was detected between the two treatment groups. The local and distant failure rates were, respectively, 19% and 40% in patients who had undergone radiotherapy and early androgen deprivation and 20% and 36% in patients who received radiotherapy alone. Cancer mortality was similar, with 35% and 30% of deaths in the former and latter group, respectively. Death for intercurrent disease, however, was significantly more frequent (p = 0.03) in patients treated with radiotherapy and hormones (19%) than in those who received radiotherapy alone (8%). Actuarial analysis of both metastasis-free and disease-free survival detected no difference between the two treatment groups, with 10-year rates of 53.3% and 42.5%, respectively, in the radiation-alone group and 45.5% and 47%, respectively, in the radiation-plus-androgen deprivation group. A statistically significant difference (p = 0.03) in overall survival in favor of patients treated with radiotherapy alone was noted, with a 10-year rate of 47%, compared with 26% observed in the radiotherapy-plus-androgen deprivation group. In conclusion, results of our study confirm numerous reports based on retrospective analyses that failed to show any benefit of hormonal management adjuvant to a definitive irradiation. The disappointing finding was the significantly better overall survival in patients who underwent radiotherapy alone.

Adenocarcinoma↗

Alcohol consumption and total estradiol in premenopausal women.

The present paper analyzes the relation between alcohol intake and serum total estradiol in premenopausal women while attempting to control or reduce several sources of variability of serum estradiol. Sixty premenopausal women were recruited, and alcohol intake was estimated by a semiquantitative questionnaire. Interviews, anthropometric measurements, and blood drawings (after overnight fasting) were conducted twice, 1 year apart. Both blood samples were obtained on the same day of the luteal phase of the cycle, in the same month and in the same hour and minute of the day. Samples from the first drawing were stored at -80 degrees C. Serum from both drawings was assayed simultaneously and in blind fashion. A significant association between alcohol intake and estradiol was found when estradiol was averaged across the two visits (Spearman's r = 0.29; P < 0.05). To control for intraindividual variability of estradiol over time, participants were then divided into tertiles of hormone distribution for each of the two sets of measurements and classified based on their consistency in estradiol across the two visits. Women showing consistently high estradiol levels at both visits were characterized by a significantly higher alcohol intake (92.8 g/week) in comparison with those showing consistently low estradiol at both visits (31.6 g/week). Furthermore, the prevalence of drinkers in the group with consistently high estradiol was significantly higher than in the group with consistently low estradiol. The present report indicates that drinkers seem to be characterized by consistently higher estradiol than nondrinkers, and that when the variability of estradiol in premenopause is considered, it is possible to identify a relationship between alcohol intake and estradiol.

Adult↗

[Pulmonary hypertension in patients with left ventricular dysfunction studied with contrast-enhanced Doppler echocardiography: relations with diastolic parameters and prognostic implications].

In patients with left ventricular dysfunction, the prognostic value of both pulmonary hypertension and mitral flow patterns has been recognized. However, the effect of the association of different degrees of pulmonary hypertension on prognosis and the corresponding left ventricular diastolic dysfunction is not clear. Accordingly, we considered the impact on survival of a categorization based on the relationship between pulmonary artery pressure and left ventricular diastolic dysfunction, as assessed by mitral and pulmonary venous flow analyses. Transthoracic Doppler echocardiography was carried out in 92 patients with ejection fraction < 45%, pulmonary artery systolic pressure > 25 mmHg and sinus rhythm. Tricuspid regurgitant velocity and Doppler parameters derived from transmitral and pulmonary venous flows were evaluated. In the case of inadequate baseline tracings, weak or poor Doppler signals were enhanced by intravenous injection of a galactose-based contrast agent (Levovist 8 ml suspension at a concentration of 400 mg/ml). To select those whose pulmonary hypertension was either proportional or unproportional to left side filling pressures, patients were divided as follows: Group 1 (n = 69) with low discrepancies and Group 2 (n = 23) with marked discrepancies between Doppler estimates of pulmonary artery systolic pressure and left side filling abnormalities. The patients of each group were also classified according to their mitral flow pattern: abnormal relaxation, pseudonormal and restrictive. Mean pulmonary artery systolic pressure was 49 +/- 16 mmHg in the total population, 43 +/- 11 mmHg in Group 1 and 68 +/- 14 mmHg in Group 2 (p < 0.0001). Several mitral and pulmonary venous flow variables significantly correlated with pulmonary artery systolic pressure in the total population and in the study groups. The best correlations were observed in Group 1 as regards the ratio of reverse-to-forward atrial wave duration (r = 0.83), E wave deceleration rate (r = 0.81), E wave deceleration time (r = -0.81) and the systolic fraction of pulmonary venous flow peak velocities (r = -0.75). In Group 1, the lower heart failure-free survival rate at 10 months was observed in patients with restrictive pattern (68%) as opposed to those with pseudonormal (94%) and abnormal relaxation patterns (97%). The overall heart failure-free survival rate in Group 2 was 86%. In conclusion, the classification according to the relationship between pulmonary hypertension and the alterations of left chamber filling may contribute to the prognostic stratification of patients with left ventricular dysfunction. The patients with pulmonary hypertension proportional to the increase in left chamber filling pressures and restrictive pattern exhibited the worst prognosis.

Aged↗

Conjugal amyotrophic lateral sclerosis: toxic clustering or change?

We describe a southern Italian couple, married for 28 years, who developed amyotrophic lateral sclerosis (ALS) within 30 months of each other. They had drunk water taken from an artesian well for nearly thirty years. Samples of the water were investigated in the search for heavy metals and pesticides using high performances liquid chromatography, gas chromatography and absorption spectrometry. No heavy metals, pesticides or known environmental toxic substances were found in significant concentration. This would seem to support the view that conjugal ALS in Caucasians is due to mere coincidence.

Amyotrophic Lateral Sclerosis↗

Motor evoked potentials and disability in secondary progressive multiple sclerosis.

BACKGROUND: To investigate the mechanisms underlying disability in multiple sclerosis (MS), 40 patients with the relapsing-remitting form of the disease and 13 patients with secondary progressive MS underwent multimodal evoked potential (EP), motor evoked potential (MEP), and spinal motor conduction time evaluation. Clinical disability was evaluated by the expanded disability status scale (EDSS) and functional system scales. In secondary progressive MS patients, magnetic resonance imaging (MRI) was used to obtain a semiquantitATive estimate of the total lesion load of the brain. RESULTS: Spinal motor conduction time was significantly longer in secondary progressive MS patients than controls (p < 0.001) and relapsing-remitting MS patients (p < 0.05), but did not differ between relapsing-remitting patients and controls. Spinal motor conduction times also correlated directly with EDSS scores (p < 0.001) and pyramidal functional system scores (p < 0.001). Brain lesion load (4960.3 +/- 3719.0 mm2) and the total number of lesions (67.7 +/- 37.0) in secondary progressive MS did not correlate with disability scores. For the following EPs, the frequencies of abnormalities were significantly higher in secondary progressive MS patients than relapsing-remitting patients: visual evoked potentials (p < 0.05), somatosensory evoked potentials and upper limb motor evoked potentials (p < 0.01), and brainstem auditory evoked potentials, lower limb somatosensory evoked potentials and lower limb motor evoked potentials (p < 0.001). CONCLUSIONS: These findings suggest that disability in secondary progressive MS patients is mainly due to progressive involvement of corticospinal tract in the spinal cord.

Adult↗

Estimation and projections of colorectal cancer trends in Italy.

BACKGROUND: Occurrence of and prognosis for tumours of the colon and rectum are thought to be changing rapidly due to simultaneous changes in risk factor prevalence, early diagnosis and treatment. In this paper time trends of morbidity, survival and mortality for colorectal cancer during the period 1970-1990 are estimated and analysed. METHODS: Mortality trends were obtained from official death certificates. Relative survival rates were computed from population-based cancer registries. Incidence and prevalence rates were estimated from mortality and survival data. RESULTS: Incidence rates were increasing during the period considered, with a lower rate of increase for the youngest birth cohorts. Relative survival rates of both colon and rectum cancers were higher for women, and for younger age groups, and were positively associated with period of diagnosis. No significant survival difference among the cancer registries used was found. A total of about 155,000 prevalent cases, 40% of which had been diagnosed > or = 7 years before, were estimated in the Italian population for the year 1990. Mortality rates were slightly increasing for men and stable for women. Projections of colorectal cancer trends to the year 2000 indicate major expected rises in both incidence and prevalence. CONCLUSION: Colorectal cancer represents a problem of growing impact for health services in Italy. This conclusion can probably be extended to many developed countries.

Adult↗

Serum sex hormone levels after menopause and subsequent breast cancer.

BACKGROUND: High levels of androgens and estrogens have been reported to be associated with breast cancer. However, the multiplicity of factors that influence hormone levels and methodologic issues complicate the study of the relationship between steroid sex hormones and breast cancer. PURPOSE: Using an improved study design, we assessed prospectively the relationship between the principal steroid sex hormones in serum and the subsequent occurrence of invasive breast cancer in postmenopausal women. METHODS: Four thousand fifty-three healthy postmenopausal women aged 40-69 years, were enrolled from June 1987 through June 1992 in a prospective investigation of hormones and diet in the etiology of breast tumors (ORDET study) as part of a larger volunteer cohort of 10 788 premenopausal and postmenopausal women from Varese Province, northern Italy. At recruitment, blood samples were taken between 8:00 AM and 9:30 AM (after overnight fasting), and sera were preserved in -80 degree Celsius freezers. Women who had received hormone treatment in the 3 months prior to enrollment, who had bilateral ovariectomy, or who had a history of cancer or liver disease were not recruited. Twenty-five women in the final eligible cohort of postmenopausal women developed histologically confirmed, invasive breast cancer during the first 3.5 years of follow-up for the cohort (13 537 women-years). For each case subject, four control subjects were randomly chosen after matching for factors possibly affecting hormone preservation in serum. One case subject and eight control subjects were excluded because premenopausal hormonal patterns were found; thus, after also excluding the four control subjects matched to the ineligible case subject, we included 24 case and 88 control subjects. In the spring of 1994, stored sera of case and control subjects were assayed in a blinded manner for dehydroepiandrosterone sulfate and estradiol (E2) by in-house radioimmunoassay and for total and free testosterone and sex hormone-binding globulin by commercially available nonextraction iodination kits. Mean differences in risk factors were tested by analysis of variance for paired data. Relative risks (RRs) were estimated by conditional logistic regression analysis. All P values resulted from two-sided tests. RESULTS: Age-adjusted mean values of total testosterone, free testosterone, and E2 were significantly higher in case subjects than in control subjects: total testosterone, 0.34 ng/mL versus 0.25 ng/mL (P<.001); free testosterone, 1.07 pg/ml versus 0.77 pg/mL (P= .006); and E2, 25 pg/mL versus 22 pg/mL (P= .027). Age-adjusted RRs for breast cancer in increasing tertiles were as follows: for total testosterone, 1.0, 4.8, and 7.0 (P for trend =.026); for free testosterone, 1.0, 1.8, and 5.7 (P for trend=.005); and for total E2, 1.0, 7.1, and 5.5 (P for trend= .128). CONCLUSIONS AND IMPLICATIONS: This prospective study provides further evidence in support of the already established association between elevated estrogen levels and breast cancer. Even more importantly, it provides new evidence that high serum testosterone levels precede breast cancer occurrence.

Adult↗

Survival for colon and rectal cancer in a population-based cancer registry.

Dukes' stage is the most powerful indicator of patient outcome for colorectal cancer. Several cancer survival studies have considered other prognostic variables, but results are often conflicting. We sought to assess the independent value of several clinical and morphological variables in defining colorectal cancer specific survival. 397 colorectal cancer patients diagnosed from 1984 to 1986, and registered in a large bowel cancer registry instituted in a local health district of Northern Italy, were actively followed-up until 31 December 1991. Univariate and multivariate survival analyses were carried out in colon and rectal cancer cases, separately, using the actuarial life-table method and Cox proportional hazard regressions. Crude and specific 5-year survival rates were 37.5 and 41.4%. In univariate analysis, TNM (tumour, nodes and metastases) stage was the strongest predictor of prognosis in both sites. Other variables significantly related to survival were age of patient at diagnosis and pattern of tumour growth in colon cancer, type of differentiation and pattern of tumour growth in rectal cancer. In multivariate analyses, after adjusting for stage, age had a weak but significant negative effect on colon cancer survival, whereas rectal tumours with the infiltrating type of growth had a significantly worse prognosis than those with the expanding type. Colorectal cancer survival should be analysed in the main large bowel subsites in order to define high-risk groups within each TNM stage category.

Aged↗

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.

Adult↗

Reliability of serum hormones in premenopausal and postmenopausal women over a one-year period.

Serum hormones have been intensively investigated in association with several chronic diseases, but limited information exists on the reliability of a number of hormone determinations. The one-year reproducibility of dehydroepiandrosterone sulfate (DHEAS), total and free testosterone, total estradiol, insulin, C-peptide, and prolactin was studied in 60 premenopausal and 47 postmenopausal women recruited in Varese province, Italy, 1991-1992. The hormonal determinations were made in blood samples collected twice, one year apart, after 12-h fast, in the same month, day, and hour and for premenopausal women on the same day of the luteal phase of the menstrual cycle. Samples from the first drawing were stored at -80 degrees C. Samples from both drawings were assayed simultaneously and in blind fashion. Total estradiol in postmenopause was not evaluated for limitation in the sensitivity of the laboratory method. The intraclass correlation coefficient in premenopausal women was 0.85 for DHEAS, 0.60 for total testosterone, 0.66 for free testosterone, 0.81 for insulin, 0.83 for C-peptide, 0.40 for prolactin, and 0.06 for total estradiol. In postmenopausal women, the coefficient was 0.90 for DHEAS, 0.88 for total testosterone, 0.71 for free testosterone, 0.67 for insulin, 0.73 for C-peptide, and 0.18 for prolactin. These data indicate that total estradiol measured during the luteal phase has a poor intraindividual reproducibility over time, and these findings may have important implications in studies of hormones in the etiology of chronic disease.

Adult↗

[Incidence and prevalence of digestive system tumors: data from Italian tumor registries].

In incidence data from 10 cancer registries in Italy, cancers of digestive organs make up 20-25% of all cancers. In incidence of oral cavity, pharynx, oesophagus and colorectal cancer is higher in the North. The highest incidence rates for stomach cancer (among the highest in Europe) are in Centre-North. Liver cancer, on the contrary, is one of few cancers with the highest frequency in the South. The first observed prevalence data measured from Italian cancer registries refer to patients with colorectal cancer recorded in Varese province in 1976-87 period and followed up to 1988. Including those cases with less than 12 years from diagnosis, they were about 200 per 100,000: more than 60% aged between 60 and 80 years.

Aged↗

[Survival for digestive system tumors: Italian population-based data and international comparisons].

Survival for malignant tumour of the upper digestive tract, oesophagus, stomach and pancreas are analysed from the data of 5042 cases observed during the period 1976-1985 by the Italian cancer registries (CRs) of Varese, Latina, Ragusa and Florence. Three-year relative survival rates were 42% for patients with tumours of the upper digestive tract and 7% for those tumour of the oesophagus. Five-year relative survival for patients with stomach cancer was 20%. A worse prognosis was found for cases from the Latina and Ragusa CRs. One-year relative survival for patients with pancreatitic cancer was 17%. Younger age, histologic confirmation, period of diagnosis (for upper tract, stomach and pancreatitic cancers), and female gender (for tumours of the upper tract) resulted as positively associated to survival.

Adolescent↗

[Survival for tumors of the colon and the rectum in Italy].

In population based from four Italian cancer registries (Varese, Modena, Latina, Ragusa), five-years relative survival was 34% for colon cancer patients (no. = 1864) and 28% from rectum cancer patients (no. = 1117). However, rectum cancer patients showed higher survival rates in the first year of follow-up, which is possibly due to earlier diagnosis for sites more accessible to clinical examination. For colorectal cancer, age was an important prognostic factor, both in univariate and in multivariate analysis, adjusting for competitive mortality, sex, geographical area and year of diagnosis. In the same multivariate analysis, the prognosis was better for women, significantly for colon cancer and the excess death risk was reduced by 25-30% from 1978-79 to 1984-85. No significant differences were found among different geographical areas, possibly because of the low number of patients from some of the participating cancer registries.

Adult↗

Comparisons of colon-cancer survival among European countries: The Eurocare Study.

Under the aegis of EUROCARE, a European Union project to assemble survival data from population-based cancer registries and analyze them according to standardized procedures, we have investigated and compared colon-cancer survival in 10 European countries. We analyzed 68,283 colon-cancer cases diagnosed between 1978 and 1985 and followed for at least 6 years. After calculating relative survival, putative factors prognostic for survival were investigated by univariate and multiple-regression analyses. Important intercountry colon-cancer survival differences exist within Europe, which are not explained by methodological differences, nor by demographic confounders. In patients aged 60 to 69, the mean European 5-year cumulative relative survival was 40%. Switzerland, Finland and The Netherlands had significantly higher 5-year relative survival, while one area in the UK and Cracow in Poland had significantly lower survival than this European estimate. Prognosis improved over time: from 1978 to 1985, the risk of death was reduced by about 4% per year in all countries studied. Age at diagnosis is inversely related to prognosis. Differences in health provision and hence in quality of care and stage at presentation seem largely responsible for the differences in colon-cancer survival found in the EUROCARE countries.

Adult↗

Estimation and projections of stomach cancer trends in Italy.

Mortality data from official sources, and survival data from population-based cancer registries, are used for the estimation of incidence and prevalence of stomach cancer. Time trends of morbidity, survival, and mortality during the period 1970-90 are presented and analyzed. Incidence rates were decreasing during the considered period, but the rate of decrease was slowing down during the last decade. Almost stable rates, and even slightly increasing for women, were estimated for the youngest cohorts. Relative survival for stomach cancer was higher for women and for young ages; it was associated positively with period of diagnosis, and presented a significant South-North geographic gradient. Prevalence was estimated as decreasing during the period 1970-80, but increasing during the successive decade, due to both better survival and population aging. Projection of stomach cancer morbidity and mortality to the year 2000 showed that the disease should still be considered in Italy as a major public health problem.

Adult↗