Lorenzo Gafà

Histology of aberrant crypt foci in the human colon

Aberrant crypt foci (ACF) have been identified in the methylene‐blue stained mucosa of the human colon. Some lines of evidence suggest that ACF may be precursors of colon cancer. The objective of the present study was to establish morphological criteria able to define and classify ACF in histological sections. Twenty‐four colectomy specimens were collected after operation for colorectal cancer and fixed in 10% formalin. Strips of grossly normal mucosa were stained in a 0.2% solution of methylene blue in saline for 5–10 min. The strips were measured, put on a glass slide and observed under a light microscope at ×25. One hundred and fourteen ACF identified by topology were sectioned parallel to the muscularis mucosae. Eighty‐four ACF were evident at histological examination and could be classified into three main groups: group A (61 ACF, 72.6%) including foci whose epithelial cells had regular nuclei, with only mild or focal crowding but no stratification, no mucin depletion and no dysplasia; group B (16 ACF, 19.1%), in which features of hyperplasia were evident; and group C (seven ACF, 8.3%) including foci with enlarged, crowded and stratified nuclei, mucin depletion, frequent mitoses, and evident dysplasia, diffuse or focal (mild in five cases, moderate in two) representing microadenomas. Finally, hyperplastic foci were significantly larger than foci of group A and C. Group B ACF were also more frequent in the rectum than in the colon. In conclusion, selected histological features allow the definition of groups of ACF, which may represent sequential steps in the development of human colorectal tumours.

Incidence of second primary cancers in three Italian population-based cancer registries

This is the first population-based study carried out in a southern European region to evaluate the risk of a cohort of cancer patients for developing further cancers. The Tuscany Tumour Registry, the Ragusa Cancer Registry and the Cancer Registry of Romagna, three of the 14 population-based cancer registries active in Italy, were involved in the present study. Overall, 19,252 incident cases of cancer of the female breast, and of the colon, rectum, lung and stomach were followed-up for 48 358.3 person-years. Only second metachronous cancers were considered. Controlateral breast cancers were analysed separately. Multiple primaries (MPs) were defined according to the IACR-IACR rules. The observed (O) numbers of MPs were compared with those expected (E) from age-, sex- and registry-specific incidence rates. Overall, 463 MPs were diagnosed (O/E = 0.87, P < 0.001). The O/E ratios for cancers of the colon (O/E = 0.66), rectum (O/E = 0.72) and all sites combined (O/E = 0.78) in males were significantly lower than expected. The deficit of observed MPs was significant during the first period (2-12 months) and increased over time. Patients over 65 years of age had a significant lower risk of MP, whereas young cancer patients had significantly higher risks for all cancers and for female breast cancer. Male lung cancer patients had a significantly reduced O/E ratio for stomach cancer (O/E = 0.21). Rectal cancer patients had reduced risks of developing stomach cancer and tumours of all sites combined and a 3-fold increased risk of kidney cancers. Colon cancer patients had an overall reduction in risk of MPs, but female colon cancer patients had a significantly increased risk for tumours of the ovary and small intestine; no significant results were found for primary stomach cancers. Female breast cancer patients had a significantly increased risk of rectal cancer (O/E = 1.97), and when synchronous and bilateral breast cancers were considered, significant overall increases in risk were seen for all cancer sites (O/E = 1.6) and for rectal (O/E = 2), and especially for breast cancers (O/E = 3). The cohort analysed had a lower risk of developing further independent tumours than the general population. Several artefacts may have biased these results: the exclusion of synchronous cancers greatly reduced the overall MP risk, and the age-related differences may have been due to reduced medical surveillance and diagnostic aggressiveness. We have confirmed the increased risk for kidney cancers in rectal cancer patients and the association between cancers of the colon and ovary. The significantly increased risk for rectal cancer in female breast cancer patients is probably due to hormonal and dietary factors. For female breast cancer patients, controlateral breast cancer represented the highest risk. The increased risk of cancer of the small intestine in patients with colon cancer may be due to overdiagnosis within increased medical surveillance.

Occupation and skin cancer: the results of the HELIOS-I multicenter case-control study

BackgroundNon-melanoma skin cancer (NMSC) is the most frequent tumour among Caucasian populations worldwide. Among the risk factors associated with this tumour, there are host-related factors and several environmental agents. A greater likelihood of high exposure to physical agents (with the exception of solar radiation) and chemical agents depends on the work setting. Our objective is to evaluate the role of occupational exposures in NMSC, with special emphasis on risk factors other than solar radiation and skin type.MethodsWe analysed 1585 cases (1333 basal cell carcinoma (BCC) and 183 squamous cell carcinoma (SCC)) and 1507 controls drawn from the Helios-I multicenter study. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression mixed models.ResultsFor NMSC as a whole (both histological types), miners and quarrymen, secondary education teachers, and masons registered excess risk, regardless of exposure to solar radiation and skin type (OR 7.04, 95% CI 2.44–20.31; OR 1.75, 95% CI 1.05–2.89 and OR 1.54, 95% CI 1.04–2.27, respectively). Frequency of BCC proved higher among railway engine drivers and firemen (OR 4.55; 95% CI 0.96–21.57), specialised farmers (OR 1.65; 95% CI 1.05–2.59) and salesmen (OR 3.02; 95% CI 1.05–2.86), in addition to miners and quarrymen and secondary education teachers (OR 7.96; 95% CI 2.72–23.23 and OR 1.76; 95% CI 1.05–2.94 respectively). The occupations that registered a higher risk of SCC (though not of BCC) were those involving direct contact with livestock, construction workers not elsewhere classified (OR 2.95, 95% CI 1.12–7.74), stationary engine and related equipment operators not elsewhere classified (OR 5.31, 95% CI 1.13–21.04) and masons (OR 2.55, 95% CI 1.36–4.78).ConclusionExposure to hazardous air pollutants, arsenic, ionizing radiations and burns may explain a good part of the associations observed in this study. The Helios study affords an excellent opportunity for further in-depth study of physical and chemical agents and NMSC based on matrices of occupational exposure.

Variations in the survival of adult cancer patients in Italy.

Aims As part of the ITACARE project, the present study analyzed and compared population-based data on the survival of adult cancer patients in Italy, according to sex, age, period of diagnosis and geographical area. Methods Nine Italian population-based cancer registries provided data on all their cancer patients (total 90,431 cases) followed for at least 5 years and diagnosed during the period 1978–1989. About 10% of the Italian population is covered by these registries. The data was analyzed by means of a multivariate model. Results The major findings were that there was a general improvement in 5-year relative survival over the study period (from 33% to 39%) and that there were significant differences in survival between different areas of the country, particularly for cancer sites which respond well to treatment. In general, the area covered by the Ragusa (Sicily) registry was characterized by significantly worse survival than other registry populations. Other important findings were that for all malignant cancer sites 5-year relative survival decreased with age from 50% for the youngest age class (15–44 years) to 27% for the oldest age class (75+ years) and that women have a better prognosis for most cancer sites (overall 5-year relative survival in women 48% vs 32% in men). Conclusions The significant regional differences in survival may reflect unequal provision of care, particularly between northern-central Italy and the south. The reasons for the general survival improvement with time are not completely understood, whereas the marked overall sex difference is related to the fact that the commonest cancer in women (breast cancer) is eminently more treatable than the commonest malignancy in men (lung cancer). The unfavorable trend with increasing age may be due to increasing difficulty in applying complete therapy protocols as general health declines, sometimes in relation to an advanced cancer stage at diagnosis.

What reasons lie behind long-term survival differences for gastric cancer within Europe?

BACKGROUND Wide geographic variations in survival for gastric cancer in Europe have been reported. The aim of this study was to analyse the effect of stage at diagnosis, treatment and cancer characteristics on long-term survival for gastric cancer in populations covered by cancer registries. METHODS We analysed survival in 4620 cases of gastric cancer from 17 European population-based cancer registries from 8 countries. Univariate and multivariate regression of relative survival were performed. RESULTS Five-year relative survival varied between 10.6% and 24.0%, while 10-year survival ranged from 7.7% to 23.0%. After adjustment for age and sex, the regional excess hazard ratio (EHR) of death was significantly higher in Ragusa, Granada, Yorkshire, Slovakia, Slovenia and Poland than in France, Northern Italy, The Netherlands and the Basque Country. After further adjustment for surgical resection versus no resection (a proxy of stage), the EHR of death remained significantly higher only in Granada and Yorkshire than in the reference country (France). After adjustment for stage, the EHR was significantly higher only in Yorkshire (EHR: 1.51; 95% confidence interval (CI): 1.29-1.77). The EHR in this area was limited to the first year following diagnosis. CONCLUSION Differences across Europe in gastric cancer survival depend to a large extent on differences in stage at diagnosis. However they do not explain all variations. Quality of management and treatment can explain some differences.

Survival in adult Italian cancer patients, 1978-1989

Aims To present a systematic analysis of population-based cancer patient survival in Italy. Methods Population-based survival data have been made available from 10 Italian cancer registries within the ITACARE project. Data, collected and validated using a common protocol, included over 100,000 patients with cancer diagnosed between 1978 and 1989. Multivariate weighted analysis was used to provide relative survival estimates attributable to Italy at national level. Results Results are presented, according to a systematic frame, as the main object of the ITACARE study, involving crude and relative survival figures for adult Italian cancer patients, by age, sex, period of diagnosis and registry area. An estimate with reference to Italy as a whole is also presented by cancer site and for all malignant neoplasms combined. Age-standardized relative survival figures are presented to allow comparisons between Italian registries and also to give a basis for international comparisons with countries involved in the EUROCARE study. Conclusions For the fist time, population-based survival of cancer patients is made available in Italy on a large scale analysis of data from all the Italian cancer registries in a combined action. Estimates of cancer patient survival at a national level in Italy allow proper international comparisons with European countries and give elements of evaluation and discussion on the performance of the Italian health care system.

Oral Contraceptive Use and BRCA Penetrance: A Case-Only Study

Background: Women with deleterious mutations in BRCA genes are at increased risk of breast cancer. However, the penetrance of the genetic trait may be regulated through environmental factors. This multinational case-only study tested the interaction between oral contraceptive use and genetic susceptibility in the occurrence of breast cancer. Methods: We recruited 3,123 patients diagnosed with breast cancer before the age of 45 years. Participants were classified according to their probability of carrying a BRCA mutation on the basis of their family history of breast and ovarian cancer. According to a case-only approach, the frequency of relevant exposures among breast cancer cases with high probability of BRCA mutation (“genetic cases”) was compared with the frequency of the same exposures among breast cancer cases with a low probability of BRCA mutation (“sporadic cases”). The interaction odds ratios (OR) and 95% confidence intervals (CI) for oral contraceptive use were estimated by unconditional logistic regression, after controlling for potentially confounding variables. Results: The analysis was carried out comparing 382 “genetic” and 1,333 “sporadic” cases. We found a borderline significant interaction between genetic breast cancer and oral contraceptive use for ever users compared with never users (OR, 1.3; 95% CI, 1.0-1.7). The greatest interaction OR was found for women who started using pill at 18 to 20 years (OR, 1.6; 95% CI, 1.1-2.3). Conclusion: These results suggest that BRCA mutation carriers, as well as women with a significant family history of breast and ovarian cancer are more vulnerable to exogenous hormones in oral contraceptives. (Cancer Epidemiol Biomarkers Prev 2009;18(7):2107–13)

Survival of patients with cancer of the stomach, colon and rectum, lung and breast in Ragusa, Sicily.

Survival of 1747 patients with cancer of the stomach, colon/rectum, lung and female breast was investigated on incident cases registered by the Ragusa Cancer Registry, covering the Province of Ragusa (275,000 inhabitants) between 1981 and 1986. Cases known from the death certificate only were excluded. Date of death was obtained by a linkage with death certificates issued for Ragusa residents. Living status was assessed directly at the Registrars Office. Analysis was performed also by sex, age group and presence of histologic verification. Relative survival at 5 years of Ragusa cancer cases was of the same order of magnitude as that observed in the U.S.A. (1980) and in Switzerland (1970-1980). However, the slight differences observed were mostly in favor of the Swiss and American patients. Sex did not significantly influence survival, but younger patients survived longer than older ones. Lack of histologic verification was associated with poor survival.

Risk factors of female cancers in ragusa population (sicily) - I. Endometrium and cervix uteri cancers

A case-control study on breast, cervix and endometrium cancer cases registered in Ragusa between January 1, 1983 and June 30, 1985 has been conducted. Information on risk factors has been obtained by means of a structured questionnaire.Risk factors for endometrium cancer were: few children (1–2 vs > 4 OR 15.18, 95%CL 1.96–117.64), oestrogenic treatment (OR 2.20, 95%CL 1.05–4.90), obesity (Quetelet index >30 vs <22 OR 10.42, 95%CL 1.30–83.86), family history (OR 2.87, 95% CL 1.05–7.83).Risk factors for cervix uteri cancer were: multiple abortions (>2 vs 0 OR 9.87, 95%CL 1.46–66.66), no contraception (OR 8.33, 95%CL 2.38–25.00), younger age of mother at birth (OR 6.89, 95%CL 1.71–27.70).Age at menarche, age at menopause and years of fertile life were not found to be related to either endometrium or cervix uteri cancer.The existence of influencing differences (ancestry, environment, lifestyle) has been postulated.

Risk factors of female cancers in Ragusa population (Sicily). 2. Breast cancer

A case-control study on breast, cervix and corpus uteri cancer cases registered in Ragusa between January 1, 1983 and June 30, 1985 has been conducted. Information on risk factors has been obtained by means of a structured questionnaire.Risk factors for breast cancer were: few pregnancies (1–2 vs > 4 OR 2.14, 95%CL 1.13–4.04), few children (for postmenopausal only, chi trend 4.84), previous breast disease (OR 1.97, 95%CL 1.20–3.23), family history (OR 3.57, 95%CL 1.92–6.63), alcohol (OR 1.68, 95%CL 1.12–2.53), high socioeconomical status (1 vs 4 OR 2,93, 95%CL 1.22–70.03). A protective role was evident for: early age at first birth (for premenopausal only, <20 vs >20 OR 0.11, 95%CL 0.01-0.90), previous ovary disease (OR 0.26, 95%CL 0.08–0.88).Age at menarche, age at menopause, years of fertile life and breast feeding were not found to be related to breast cancer. A different distribution of risk factors among cases with and without family history has been suggested.A synoptic table shows the distribution of the most important risk factors of the three investigated female cancers in the Ragusa population, reported in the present and in an accompanying paper.