Mario Fusco

Pattern of cancer risk in persons with AIDS in Italy in the HAART era

A record-linkage study was carried out between the Italian AIDS Registry and 24 Italian cancer registries to compare cancer excess among persons with HIV/AIDS (PWHA) before and after the introduction of highly active antiretroviral therapy (HAART) in 1996. Standardised incidence ratios (SIR) were computed in 21951 AIDS cases aged 16–69 years reported between 1986 and 2005. Of 101 669 person-years available, 45 026 were after 1996. SIR for Kaposi sarcoma (KS) and non-Hodgkin lymphoma greatly decreased in 1997–2004 compared with 1986–1996, but high SIRs for KS persisted in the increasingly large fraction of PWHA who had an interval of <1 year between first HIV-positive test and AIDS diagnosis. A significant excess of liver cancer (SIR=6.4) emerged in 1997–2004, whereas the SIRs for cancer of the cervix (41.5), anus (44.0), lung (4.1), brain (3.2), skin (non-melanoma, 1.8), Hodgkin lymphoma (20.7), myeloma (3.9), and non-AIDS-defining cancers (2.2) were similarly elevated in the two periods. The excess of some potentially preventable cancers in PWHA suggests that HAART use must be accompanied by cancer-prevention strategies, notably antismoking and cervical cancer screening programmes. Improvements in the timely identification of HIV-positive individuals are also a priority in Italy to avoid the adverse consequences of delayed HAART use.

Lactase Persistence Versus Decline in Human Adults: Multifactorial Events Are Involved in Down-regulation After Weaning

BACKGROUND & AIMS In nonhuman mammals, lactase activity declines during or after weaning. In contrast, about one half of the human species maintains high lactase activity even in adulthood. To clarify this difference, this study examined some parameters for which contrasting observations have been reported in connection with lactase decline. METHODS Lactase activity, lactase messenger RNA (mRNA) levels, and in vitro lactase biosynthesis were determined in normal jejunal samples from a large group of white adults, all born in or near Naples. RESULTS Of 44 individuals, 10 were lactase persistent and 34 were hypolactasic. Biosynthesis of prolactase correlated well with lactase mRNA levels, indicating transcriptional control; it did less so with steady-state lactase activity. Examination of lactase mRNA levels and lactase activity/lactase mRNA ratios revealed a heterogeneous pattern of lactase mRNA level, lactase synthesis, and activity in both lactase persistent and hypolactasic subjects. CONCLUSIONS Both transcriptional and posttranscriptional factors cause the decline of intestinal lactase. This probably explains the multifarious observations that most studies on adult-type hypolactasia have reported. The single overriding factor distinguishing lactase-persistent subjects from hypolactasic subjects is the high rate of lactase biosynthesis.

Cancer incidence in people with AIDS in Italy

People with HIV/AIDS (PWHA) have increased risk of some cancers. The introduction of highly active antiretroviral therapies (HAART) has improved their life expectancy, exposing them to the combined consequences of aging and of a prolonged exposure to cancer risk factors. The aim of this study was to estimate incidence rates (IR) in PWHA in Italy, before and after the introduction of HAART, after adjusting for sex and age through direct standardization. An anonymous record linkage between Italian AIDS Registry (21,951 cases) and Cancer Registries (17.3 million, 30% of Italian population) was performed. In PWHA, crude IR, sex‐ and age‐standardized IR and age‐specific IR were estimated. The standardized IR for Kaposi sarcoma and non‐Hodgkin lymphoma greatly declined in the HAART period. Although the crude IR for all non‐AIDS‐defining cancers increased in the HAART period, standardized IR did not significantly differ in the 2 periods (352 and 379/100,000, respectively). Increases were seen only for cancer of the liver (IR ratio = 4.6, 95% CI: 1.3–17.0) and lung (IR ratio = 1.8, 95% CI: 1.0–3.2). Age‐specific IRs for liver and lung cancers, however, largely overlapped in the 2 periods pointing to the strong influence of the shift in the age distribution of PWHA on the observed upward trends. In conclusion, standardized IRs for non‐AIDS‐defining cancers have not risen in the HAART period, even if crude IRs of these cancers increased. This scenario calls, however, for the intensification of cancer‐prevention strategies, notably smoking cessation and screening programs, in middle‐aged HIV‐patients.

Incidence of AIDS-defining cancers after AIDS diagnosis among people with AIDS in Italy, 1986-1998

A record linkage was carried out between the Italian National Registry of AIDS and 19 cancer registries. The aim was to evaluate the 1986 through 1998 trends in incidence rate (IR) of AIDS-defining cancers (ADCs) among persons with AIDS (PWA) in Italy overall and according to various characteristics. A steady decrease in IRs was found for Kaposi sarcoma (KS) in men between 1986–1992 (2.5 per 100 person-years [py]) and 1997–1998 (1.0 per 100 py). Conversely, the first decrease in IRs of KS in women (from 0.9 to 0.6 per 100 py) and of non-Hodgkin lymphoma in both genders (from 1.7 to 0.7 per 100 py) was seen between 1993–1996 and 1997–1998, thus pointing to a favorable impact of highly active antiretroviral therapies. The decline was consistent across different age and HIV transmission groups, but it was more marked in PWA with a CD4 count >50 cells/&mgr;L than in PWA with more severe immune suppression. As a proportion of AIDS cases, invasive cervical cancer increased from 1.5% in 1993–1996 to 2.4% in 1997–1998, but IRs after AIDS could not be evaluated. On account of the marked decline of KS in men in 1997–1998, the overall burden of ADCs in Italy became similar in both genders.

Epidemiology of viral hepatitis infections in an area of southern Italy with high incidence rates of liver cancer

Southern Italy shows the highest rates of liver cancer for Europe, mainly related to infection with hepatitis viruses. We thus described incidence rates of liver cancer and investigated prevalence and determinants of HCV and HBV infections in 4496 individuals randomly selected from the general population of the province of Naples. 7.5% was infected with HCV and 27.6% with HBV (2.2% was HBsAg-positive). Prevalence of both infections increased with age, 23.2% of those aged 65 years or older was HCV-positive and 47.9% were HBV-positive. Intravenous drug use (odds ratio (OR)=16.4 for anti-HCV and 4.7 for anti-HBc), history of blood transfusions (OR=2.8 and 1.5, respectively) and surgery, and household contacts with infected people (OR=2.1 and 1.6, respectively) increased risks for both infections. Sexual intercourse with HCV-positive individuals conveyed a 3-fold higher risk of HCV infection. This study quantified the spread of HCV and HBV in the population of southern Italy heavily affected by liver cancer.

High fasting blood glucose and obesity significantly and independently increase risk of breast cancer death in hormone receptor-positive disease.

PURPOSE We investigated the effect of fasting blood glucose and body mass index (BMI) at diagnosis on risk of breast cancer death for cases diagnosed in five Italian cancer registries in 2003-2005 and followed up to the end of 2008. METHODS For 1607 Italian women (≥15 years) with information on BMI or blood glucose or diabetes, we analysed the risk of breast cancer death in relation to glucose tertiles (≤84.0, 84.1-94.0, >94.0 mg/dl) plus diabetic and unspecified categories; BMI tertiles (≤23.4, 23.5-27.3, >27.3 kg/m(2), unspecified), stage (T1-3N0M0, T1-3N+M0 plus T4anyNM0, M1, unspecified), oestrogen (ER) and progesterone (PR) status (ER+PR+, ER-PR-, ER and PR unspecified, other), age, chemotherapy and endocrine therapy, using multiple regression models. Separate models for ER+PR+ and ER-PR- cases were also run. RESULTS Patients often had T1-3N0M0, ER+PR+ cancers and received chemotherapy or endocrine therapy; only 6% were M1 and 17% ER-PR-. Diabetic patients were older and had more often high BMI (>27 kg/m(2)), ER-PR-, M1 cancers than other patients. For ER+PR+ cases, with adjustment for other variables, breast cancer mortality was higher in women with high BMI than those with BMI 23.5-27.3 kg/m(2) (hazard ratio (HR)=2.9, 95% confidence interval (CI) 1.2-6.9). Breast cancer mortality was also higher in women with high (>94 mg/dl) blood glucose compared to those with glucose 84.1-94.0mg/dl (HR=2.6, 95% CI 1.2-5.7). CONCLUSION Our results provide evidence that in ER+PR+ patients, high blood glucose and high BMI are independently associated with increased risk of breast cancer death. Detection and correction of these factors in such patients may improve prognosis.

Long-term survival, prevalence, and cure of cancer: A population-based estimation for 818,902 Italian patients and 26 cancer types

Original, population-based estimates of indicators of long-term survival and cure in cancer patients are provided. More than a quarter of cancer patients in Italy have reached death rates similar to those of the general population. Nearly three quarters of them will not die as a result of cancer. These estimates are potentially helpful to health-care planners, clinicians, and patients.

Changes in the Incidence of Thyroid Cancer Between 1991 and 2005 in Italy: A Geographical Analysis

BACKGROUND The incidence of thyroid cancer (TC) has been increasing over the last 30 years in several countries, with some of the worldwide highest TC incidence rates (IRs) reported in Italy. The objectives of this study were to evaluate by histological subtypes the geographical heterogeneity of the incidence of TC in Italy and to analyze recent time trends for papillary thyroid carcinoma (PTC) in different cancer registries (CRs). METHODS The study included cases of TC (<85 years of age) reported to 25 Italian CRs between 1991 and 2005. Age-standardized IRs were computed for all histological subtypes of TC according to CRs. Estimated annual percent change and joinpoint regression analysis were used for analysis of PTC. RESULTS In women, IRs of PTC ranged between 3.5/100,000 in Latina and 8.5/100,000 in Sassari for the period 1991-1995 (a 2.4-fold difference) and between 7.3/100,000 in Alto Adige and 37.5/100,000 in Ferrara for 2001-2005 (a 5.1-fold difference). In men, IRs ranged between 0.7/100,000 in Latina and 3.4/100,000 in Sassari for the period 1991-1995 (a 4.9-fold difference) and between 2.0/100,000 (Alto Adige, Trento) and 10.6/100,000 in Ferrara for 2001-2005 (a 5.3-fold difference). In both sexes, IRs significantly higher than the pooled estimates emerged for the most recent period in the majority of CRs located within the Po River plain and in Latina, but they were lower in the Alpine belt. For women, CRs reported higher IRs than pool estimates showed, between 1991 to 2005, a significantly more marked annual percent change (+12%) than other CRs (+7%). For men the corresponding estimates were +11% and +8%. CONCLUSIONS The distribution of PTC does not lend support to a role of environmental radiation exposure due to the Chernobyl fallout, iodine deficiency, or (volcanic) soils. Between 1991 and 2005, wide geographic variations in the incidence of PTC and heterogeneous upward trends emerged, suggesting that the heterogeneity was a relatively recent phenomenon; this appeared to be mainly explained by variations, at a local level, in medical surveillance.

Regional inequalities in cancer care persist in Italy and can influence survival.

BACKGROUND Population-based cancer registry studies of care patterns can help elucidate reasons for the marked geographic variation in cancer survival across Italy. The article provides a snapshot of the care delivered to cancer patients in Italy. METHODS Random samples of adult patients with skin melanoma, breast, colon and non-small cell lung cancers diagnosed in 2003-2005 were selected from 14 Italian cancer registries. Logistic models estimated odds of receiving standard care (conservative surgery plus radiotherapy for early breast cancer; surgery plus chemotherapy for Dukes C colon cancer; surgery for lung cancer; sentinel node biopsy for >1mm melanoma, vs. other treatment) in each registry compared to the entire sample (reference). RESULTS Stage at diagnosis for breast, colon and melanoma was earlier in north/central than southern registries. Odds of receiving standard care were lower than reference in Sassari (0.68, 95%CI 0.51-0.90) and Napoli (0.48, 95%CI 0.35-0.67) for breast cancer; did not differ across registries for Dukes C colon cancer; were higher in Romagna (3.77, 95%CI 1.67-8.50) and lower in Biella (0.38, 95%CI 0.18-0.82) for lung cancer; and were higher in Reggio Emilia (2.37, 95%CI 1.12-5.02) and lower in Ragusa (0.27, 95%CI 0.14-0.54) for melanoma. CONCLUSIONS Notwithstanding limitations due to variations in the availability of clinical information and differences in stage distribution between north/central and southern registries, our study shows that important disparities in cancer care persist across Italy. Thus the public health priority of reducing cancer survival disparities will not be achieved in the immediate future.

Survival after cancer in Italian persons with AIDS, 1986-2005: a population-based estimation.

Background:Cancer survival in persons with AIDS (PWA) after introduction of antiretroviral therapies remains poorly characterized. The aim is to provide population-based estimates of cancer survival, overall and for the most important cancer types in PWA, and a comparison with persons without AIDS (non-PWA) affected by the same cancer. Methods:PWA with cancer at AIDS diagnosis or thereafter were individually matched with non-PWA by type of cancer, sex, age, year of diagnosis, area of living, and, for lymphomas, histological subtype. Five-year observed survival and hazard ratios (HRs) of death in PWA versus non-PWA with 95% confidence intervals (CIs) were estimated. Results:We included 2262 Italian PWA and 4602 non-PWA with cancer diagnosed during 1986–2005. Between 1986 and 1995, and 1996 and 2005, 5-year survival for all cancers in PWA improved from 12% to 41% and the corresponding HR versus non-PWA decreased from 5.1 (95% CI: 4.3 to 6.1) to 2.9 (95% CI: 2.6 to 3.3). During 1996–2005, HRs were 2.0 (95% CI: 1.4 to 2.9) for Kaposi sarcoma, 3.4 (95% CI: 2.9 to 4.1) for non-Hodgkin lymphoma, and 2.4 (95% CI: 1.4 to 4.0) for cervical cancer. HRs were 2.5 (95% CI: 2.1 to 3.1) for all non–AIDS-defining cancers, 5.9 (95% CI: 3.1 to 11.2) for Hodgkin lymphoma, and 7.3 (95% CI: 2.8 to 19.2) for nonmelanoma skin cancer. A ⩽3-fold survival difference was found for cancers of the stomach, liver, anus, lung, brain, and the most aggressive lymphoma subtypes. Conclusions:The persisting, although narrowing, gap in cancer survival between PWA and non-PWA indicates the necessity of enhancing therapeutic approaches, so that PWA can be provided the same chances of survival observed in the general population, and improving cancer prevention and screening.