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Italy needs to achieve net-zero emissions by 2050. Starting from the assumption that this only implies a technological transition, reaching this goal within the current economic model (unlimited growth) is unlikely without Carbon Capture and Storage (CCS) technology. Scientific concerns exist about CCS potentially shifting environmental burdens to future generations. The article argues that achieving net-zero emissions by 2050 hinges on embracing the principles of circular economy and agroecology. This path, however, demands a fundamental transformation of our economic and cultural models, necessitating a move away from unbridled consumerism. [ABSTRACT FROM AUTHOR]

The gray wolf (Canis lupus) expanded its distribution in Europe over the last few decades. To better understand the extent to which wolves could re-occupy their historical range, it is important to test if anthropization can affect their fitness-related traits. After having accounted for ecologically relevant confounders, we assessed how anthropization influenced i) the growth of wolves during their first year of age (n = 53), ii) sexual dimorphism between male and female adult wolves (n = 121), in a sample of individuals that had been found dead in Italy between 1999 and 2021. Wolves in anthropized areas have a smaller overall variation in their body mass, during their first year of age. Because they already have slightly higher body weight at 3–5 months, possibly due to the availability of human-derived food sources. The difference in the body weight of adult females and males slightly increases with anthropization. However, this happens because of an increase in the body mass of males only, possibly due to sex-specific differences in dispersal and/or to "dispersal phenotypes". Anthropization in Italy does not seem to have any clear, nor large, effect on the body mass of wolves. As body mass is in turn linked to important processes, like survival and reproduction, our findings indicates that wolves could potentially re-occupy most of their historical range in Europe, as anthropized landscapes do not seem to constrain such of an important life-history trait. Wolf management could therefore be needed across vast spatial scales and in anthropized areas prone to social conflicts. [ABSTRACT FROM AUTHOR]

Italy is among the European countries with the greatest plant diversity due to both a great environmental heterogeneity and a long history of man–environment interactions. Trait-based approaches to ecological studies have developed greatly over recent decades worldwide, although several issues concerning the relationships between plant functional traits and the environment still lack sufficient empirical evaluation. To draw insights on the association between plant functional traits and direct and indirect human and natural pressures on the environmental drivers, this article summarizes the existing knowledge on this topic by reviewing the results of studies performed in Italy adopting a functional trait approach on vascular plants, bryophytes and lichens. Although we recorded trait measurements for 1418 taxa, our review highlighted some major gaps in plant traits knowledge: Mediterranean ecosystems are poorly represented; traits related to belowground organs are still overlooked; traits measurements for bryophytes and lichens are lacking. Finally, intraspecific variation has been little studied at community level so far. We conclude by highlighting the need for approaches evaluating trait–environment relationship at large spatial and temporal scales and the need of a more effective contribution to online databases to tie more firmly Italian researchers to international scientific networks on plant traits. [ABSTRACT FROM AUTHOR]

Before deciding on operations involving share issuance or sale, companies or shareholders may seekto disclose information to selected investors, in order to gauge their opinion on the envisaged market operation. Despite such "market soundings" risk violating the prohibition of insider trading, selective disclosures have been partially accepted in several European jurisdictions. Market soundings have been eventually regulated in the MAR, which clarifies under which circumstances they are allowed and the position of the involved parties. This article analyses the rules on market soundings in the MAR with regard to issuance in the secondary market and accelerated bookbuildings. In this context, the question arises of whether harmonised rules on market soundings are compatible with national company law regimes. To address this issue, it will be assessed how Italian and English company law regimes react towards selective disclosures. It will be shown that a tension may still exist between uniform rules on market abuses and national company law rules, mostly with regard to directors' duties and liabilities. [ABSTRACT FROM AUTHOR]

Purpose. To determine the effectiveness of autologous platelet lysate (APL) eye drops in patients with primary Sjögren syndrome (SS) dry eye, refractory to standard therapy, in comparison with patients treated with artificial tears. We focused on the effect of APL on cornea morphology with the in vivo confocal microscopy (IVCM). Methods. Patients were assigned to two groups: group A used autologous platelet lysate QID, and group B used preservative-free artificial tears QID, for 90 days. Ophthalmological assessments included ocular surface disease index (OSDI), best corrected visual acuity (BCVA), Schirmer test, fluorescein score, and breakup time (BUT). A subgroup of patients in group A underwent IVCM: corneal basal epithelium, subbasal nerves, Langerhans cells, anterior stroma activated keratocytes, and reflectivity were evaluated. Results. 60 eyes of 30 patients were enrolled; in group A (n=20 patients) mean OSDI, fluorescein score, and BUT showed significant improvement compared with group B (n=10 patients). The IVCM showed a significant increase in basal epithelium cells density and subbasal nerve plexus density and number and a decrease in Langerhans cells density (p<0.05). Conclusion. APL was found effective in the treatment of SS dry eye. IVCM seems to be a useful tool to visualize cornea morphologic modifications. [ABSTRACT FROM AUTHOR]

The Abruzzo earthquake hit the city of L'Aquila and its surroundings on the April 6, 2009. The aim of this study is to analyze the technical features of unreinforced masonry (URM) buildings and assess their seismic behavior during the Abruzzo 2009 seismic event. The damage induced in the URM constructions of L'Aquila and the suburbs was severe and several such buildings collapsed. This study includes an overview of the dynamic characteristics of the earthquake and the seismic history of the region. The seismic performance of URM buildings is discussed on the basis of both the experience in L'Aquila and the village of Castelvecchio Subequo, during the post-emergency support to the Italian Department of Civil Protection (Dipartimento della Protezione Civile [DPC]), and the field investigation carried out with the patronage of the EU COST Action C26 and the cooperation of the PLINIVS Centre of Naples in three areas of the old city of L'Aquila. The main characteristics of URM buildings, the building behavior and damage are described and reviewed with due respect to the characteristics of the earthquake, as well as with reference to the structural and non-structural characteristics of buildings, using the Italian MEDEA procedure. [ABSTRACT FROM PUBLISHER]

For the first time, the European Court of Justice addresses a case of a cross-border transfer of registered office before the filing for insolvency. The Interedil decision makes clear that the location of a debtor' s centre of main interests ('COMI') is to be assessed as of the moment of filing for insolvency. Furthermore, the ECJ addresses the question of the evidence required to overcome the presumption that the COMI coincides with a corporation's registered office. However, behind these relevant cross-border insolvency issues hides a strange story of corporate mobility from Italy to England, which shows the need for further harmonization throughout the EU in the field of cross-border transfer of register offices. [ABSTRACT FROM AUTHOR]

Abstract: Although rice and corn are two main cash crops in Lombardy (North Italy) and their cultivation involves several thousands of farmers, risk assessment of pesticide exposure is rarely done, especially in small and medium sized enterprises. With the use of pads for environmental monitoring (OECD protocol), of pre- and post-exposure 24h urine collection for biological monitoring and of hand wash for hands’ exposure, we measured the exposure of 28 agricultural workers to propanil and terbuthylazine in real-life working conditions. In propanil applicators, median daily exposure on the clothes was 73.5μmol per worker, while the exposure on the skin was 22.4μmol. For terbuthylazine, these exposures were 37.2μmol and 0.86μmol per worker, respectively. Median excretion of the propanil metabolite (3,4-dichloroaniline) after exposure was 84nmol in 24h urine, and 13nmol for the metabolite of terbuthylazine. Risk assessment performed by comparing to the AOELs of the applied active ingredients with an estimated internal dose, obtained based on the measured levels of skin and hand exposure and the percentage of dermal absorption of the active ingredients considered showed that 4 propanil workers, and no terbuthylazine workers, were overexposed. Our study helps define and confirm relationships between different exposure determinants, which can be used in the development of tools for risk assessment of exposure to pesticides in small and medium sized enterprises. [Copyright &y& Elsevier]

Abstract: The Index of Sustainable Economic Welfare (ISEW) was introduced by Daly and Cobb in 1989 in order to integrate the information embodied in GDP. Since economic growth implies externalities and market failures, and a portion of it can be defined as “uneconomic”, the ISEW method introduces some corrections and adjustments to the GDP calculation framework. The ISEW has been calculated for a number of nations but it has been rarely applied to sub-national systems. Its calculation at the local level is important especially in case of administrative decentralization, and autonomy and responsibility of local authorities in certain fields. For this reason, a more and more comprehensive knowledge of the characteristics and peculiarities of the territorial system they manage is necessary. This paper presents the results of the ISEW calculation for Tuscany, a region in central Italy, in the period 1971–2006. This is one of the few attempts to apply the ISEW in time series at the regional level. Final results show that a discrepancy between ISEW and GDP appeared in the 1970s. Social and environmental pressures increased during the period under study making the gap equal to about 30 percent of regional GDP in 2006. The ISEW can be used also as a tool for evaluating policies, but further adjustments in calculation of certain items are considered necessary for taking into account and evaluating punctual policies. A case of energy policy is presented. [Copyright &y& Elsevier]

Emergy is a thermodynamics-based entity that enables the implementation of a holistic environmental accounting system. It contributes to identify and measure all the inputs (energy and matter) supporting a given system, expressed in a common unit, namely solar emergy joule (sej). The emergy per unit product (called unit emergy value, UEV), is a measure of the environmental cost of a given resource. It is specific of the system/process and gives information on the dynamics, components and functioning of it. This paper presents the emergy evaluation of water resources within the watershed of the river Sieve, located in the Province of Florence (Italy). Along the river, an artificial basin has been created by means of a dam to preserve water quantity and quality, and to protect the Florentine area from dangerous floods and inundations. Different UEVs of water can be identified along the course of the river, especially upstream and downstream of the dam. These values quantify both the environmental and human efforts made to ensure and regulate the presence of water at different points of the river. The UEV of water flowing in the river increases from 1.35×105 sej/g upstream, to 5.80×105 sej/g downstream of the dam, depending mainly on man-made infrastructure. Along the watershed, three different systems of extraction, purification and distribution of water have been chosen on the basis of their dimension, type and location. UEVs of water distributed and the emergy investment necessary to implement different water management strategies are presented. The value of water purified and distributed decreases from 2.00×106 sej/g for the smallest plant in the mountainous area, to 1.72×106 sej/g for the largest plant, in the city of Florence, depending on production efficiency. [Copyright &y& Elsevier]

This article focuses on the seismic behavior of the church of the Fossanova Abbey (Priverno, Italy), which represents a magnificent example of a pre-Gothic Cistercian style monument. Aiming at investigating the seismic vulnerability of such a structural typology, experimental and numeric analyses have been carried out within the large European FP6 project PROHITECH. First, detailed investigations were devoted to identify the main constructional parts and the mechanical features of the constituting materials. Then, both ambient vibration tests and numeric modal identification analyses by finite element method (FEM) were applied, allowing the detection of the main dynamic features of the church. Based on such results, a refined FEM model reproducing the dynamic behavior of the structural complex was developed. The numeric study, carried out with a limit analysis, allowed the identification of the most vulnerable parts of the church, providing also an estimation of its actual seismic vulnerability. Finally, a shaking-table test on a 1-to-5.5 reduced scale model has been carried out checking the dynamic response of the complex structure as well as the constancy of the previous numeric study. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The aim of this study was the evaluation of the impact of service screening programmes on breast cancer mortality in five regions of Italy. We conducted a matched case-control study with four controls for each case. Cases were defined as breast cancer deaths occurred not later than 31 December 2002. Controls were sampled from the local municipality list and matched by date of birth. Screening histories were assessed by the local, computerised, screening database and subjects were classified as either invited or not-yet-invited and as either screened or unscreened. There were a total of 1750 breast cancer deaths within the 50 to 74-year-old breast cancer cases and a total of 7000 controls. The logistic conditional estimate of the cumulative odds ratios comparing invited with not-yet-invited women was 0.75 (95% CI: 0.62-0.92). Restricting the analyses to invited women, the odds ratio of screened to never-respondent women corrected for self-selection bias was 0.55 (95% CI: 0.36-0.85). The introduction of breast cancer screening programmes in Italy is associated with a reduction in breast cancer mortality attributable to the additional impact of service screening over and above the background access to mammography. [ABSTRACT FROM AUTHOR]

This paper demonstrates how the results from different methods can be interpreted on the basis of a statistical approach that can help find new hints in the evaluation of sustainability at the territorial level. The SPIn-Eco Project for the Province of Siena (Italy) is an example of an environmental sustainability assessment of an area using methods that are suitable for a large system: Ecological Footprint, Greenhouse Gas Inventory, Extended Exergy Analysis, Emergy Evaluation, and Remote Sensing. The calculation of many indicators, derived from these methods, has prompted us to use a statistical method (Principal Components Analysis, PCA) to understand the degree of similarity/congruence of the indicators (here we have examined 26 of them) and the possibility of recognizing patterns or clusters in the description of the 36 municipalities that compose the Province of Siena. Among the results, unexpectedly, emergy flow and the Ecological Footprint resulted as being completely uncorrelated, apparently due to the importance that the non-renewable part of the emergy holds in the evaluation. The municipalities of the province are considerably spread out over the graphs, even though that of Siena is quite far from the rest along the first dimension. In addition, we were able to distinguish between more homogeneous districts (sets of municipalities), such as Val di Merse and Val d’Orcia, and very diverse ones, such as Val d’Elsa and Val di Chiana. [Copyright &y& Elsevier]

This paper shows how different methods can be integrated in order to provide an organic evaluation of the environmental sustainability at the territorial level. A territory is a complex, dynamic and open system where a population develops, uses resources, produces goods and services, consumes, depletes and finally obtains economic results. All these elements characterise human behaviour, which can be monitored, measured and compared to the capacity of the environment to sustain it in the long run. The SPIn-Eco Project for the Province of Siena (Italy) is described as an example of an environmental sustainability assessment of an area, and its methods (Ecological Footprint, Greenhouse Gas Inventory, Extended Exergy Analysis, Emergy Evaluation, Life Cycle Assessment (LCA) and Remote Sensing) are briefly introduced. This Project has been proposed and funded by the most important provincial administrative and financial institutions in the territory (the Administration of the Province of Siena and the Monte dei Paschi Foundation, respectively), and was designed and realised in 4 years (2001–2004) by a research team coordinated by the University of Siena. [Copyright &y& Elsevier]

The present article analyses the relationship between leadership and democracy. The concept of leadership is understood in reference to the Weberian matrix, in the sense of an asymmetrical relationship of domination by witch a governing minority impose a political mandate on the whole society. Leadership becomes relevant in a democracy when it can be practised only by and through political parties. By these, the article approaches the conditions of political leadership institutionalization in modern democracies and their relation with parliamentarian governments. Last but not least, the article analyses the institutional patterns of the Italian democracy, focusing on leadership and power processes in the Christian Democracy party between 1948 and 1992. [ABSTRACT FROM AUTHOR]

We enrolled all 2162 in situ and 21 148 invasive cases of breast cancer in 17 areas of Italy, diagnosed in 1997-2001. Rates of early cancer increased by 13.7% in the screening age group (50-69 years), and breast conserving surgery by 24.6%. Advanced cancer rates decreased by 19.4%, and mastectomy rates by 24.2%. Service screening did not increase mastectomy rates in the study population. [ABSTRACT FROM AUTHOR]

To evaluate incidence rates (IRs) of classic Kaposi's sarcoma (CKS) in Italy after the spread of AIDS, we distinguished CKS from AIDS-related KS (AKS) using an 'ad hoc' record linkage procedure between 15 Cancer Registries (CRs) (21% of the Italian population) and the national AIDS Registry. Between 1985 and 1998, 874 cases of CKS and 634 cases of AKS were diagnosed in the study areas. CKS accounted for 16 and 27% of KS cases below 55 years of age in men and women, respectively, but for 91 and 100% of those above age 55. The IRs for CKS were 1.0/ in men and 0.4/100,000 in women, but they varied between 0.3 in Umbria and 4.7 in Sassari in men, and between 0.1 in Parma and 1.7 in Sassari in women. IRs of CKS in both genders were stable between 1985-1987 and 1993-1998. In Northern and Central CRs the IR (adjusted for age and gender) for CKS was 0.5 in individuals born in the same area, but 1.6 in individuals born in Southern Italy or in the Islands (rate ratio = 3.2) suggesting that KS-associated herpesvirus, the cause of KS, is acquired early in life. [ABSTRACT FROM AUTHOR]

Objective: To determine the rate of return of patients to sport after arthroscopic autologous matrix-induced chondrogenesis (AT-AMIC) for outcomes 2 years after surgery. Design: Retrospective observational cross-sectional study. Setting: C.A.S.C.O.--Foot and Ankle Unit, Istituto Ortopedico Galeazzi, Milan, Italy. Patients and Intervention: Twenty-six consecutive patients, 65.4% male (mean ± SD age: 33.7 ± 11.0 years), that underwent AT-AMIC procedure between 2012 and 2015 were selected retrospectively. From this population, only sporting patients at amateur's level were included. Arthroscopic autologous matrix- induced chondrogenesis was proposed in patients with pain and persistent disability. Main Outcome Measures: All patients were assessed with the American Orthopaedic Foot and Ankle Score (AOFAS), physical component score of the 12-Item Short Form Health Survey (SF-12), Halasi ankle activity score, and University of California, Los Angeles (UCLA) activity scale preoperatively and at 24 months postoperatively. Results: Overall, 80.8% of the patient group returned to the same preinjury sport. The mean follow-up was 42.6 ± 10.9 months (range from 25 to 62 months). Significant differences were observed with reference to AOFAS, SF-12, Halasi, and UCLA scores at the last follow-up in patients who had undergone AT-AMIC (all, P < 0.001). Conclusions: A high percentage of patients return to their preinjury sport after AT-AMIC surgery. [ABSTRACT FROM AUTHOR]

Background and Purpose: Stereotactic Ablative Radiotherapy (SABR) is emerging as a valid alternative to surgery in the oligometastatic setting in soft tissue sarcomas (STS), although robust data are lacking. The aim of this study is to evaluate toxicity and efficacy of SABR in oligometastatic STS., Materials and Methods: This is a retrospective multicenter study including adult patients affected by stage IV STS, treated with SABR for a maximum of 5 cranial or extracranial metastases in up to 3 different organs. SABR was delivered with ablative purposes. Study endpoints were overall survival (OS), local control (LC), distant progression free survival (DPFS), time to polymetastatic progression (TTPP), time to new systemic therapy (TTNS) and toxicity., Results: From 10 Italian RT centers, 138 patients (202 metastases) treated between 2010 and 2022 were enrolled in the study. Treatment was generally well tolerated, no acute or late toxicity ≥ G3 was recorded. Median follow up was 42.5 months. Median OS was 39.7 months. Actuarial OS at 1 and 2 years was 91.5 % and 72.7 %. Actuarial LC at 1 and 2 years was 94.8 % and 88.0 %. Median DPFS was 9.7 months. Actuarial DPFS at 1 and 2 years was 40.8 % and 19.4 %., Conclusion: SABR is a safe and effective approach for the treatment of oligometastatic sarcoma. One out of 5 patients is free of progression at 2-years., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The effect of feeding supplementation on the nutritional characteristics of milk and cheese was studied in dairy sheep grazing on low mountain dry-grasslands during summer in typical sub-Mediterranean conditions of aridity. The control group (CG) of 25 sheep grazed on grass, while the experimental group (EG) of 25 sheep grazed on grass and received 600 g a day of a barley and corn mixture. Daily milk production showed a less pronounced decrease in EG than in CG ( p ˂ 0.0368). After one month of supplementation, the concentrations of retinol and α-tocopherol in milk and cheese from EG were higher than CG ( p  < 0.05). Supplementary feeding had a positive effect on the fatty acid composition of the sheep milk. For the first time, positive effects on the volatile composition were found in EG cheese, displaying lower percentages of carboxylic acids associated with the pungent and rancid odour with respect to CG.

Background: Six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) are the standard treatment for aggressive B-cell non-Hodgkin lymphoma. In the FLYER trial, we assessed whether four cycles of CHOP plus six applications of rituximab are non-inferior to six cycles of R-CHOP in a population of patients with B-cell non-Hodgkin lymphoma with favourable prognosis., Methods: This two-arm, open-label, international, multicentre, prospective, randomised phase 3 non-inferiority trial was done at 138 clinical sites in Denmark, Israel, Italy, Norway, and Germany. We enrolled patients aged 18-60 years, with stage I-II disease, normal serum lactate dehydrogenase concentration, ECOG performance status 0-1, and without bulky disease (maximal tumour diameter <7·5 cm). Randomisation was computer-based and done centrally in a 1:1 ratio using the Pocock minimisation algorithm after stratification for centres, stage (I vs II), and extralymphatic sites (no vs yes). Patients were assigned to receive either six cycles of R-CHOP or four cycles of R-CHOP plus two doses of rituximab. CHOP comprised cyclophosphamide (750 mg/m 2 ), doxorubicin (50 mg/m 2 ), and vincristine (1·4 mg/m 2 , with a maximum total dose of 2 mg), all administered intravenously on day 1, plus oral prednisone or prednisolone at the discretion of the investigator (100 mg) administered on days 1-5. Rituximab was given at a dose of 375 mg/m 2 of body surface area. Cycles were repeated every 21 days. No radiotherapy was planned except for testicular lymphoma treatment. The primary endpoint was progression-free survival after 3 years. The primary analysis was done in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of assigned treatment. A non-inferiority margin of -5·5% was chosen. The trial, which is completed, was prospectively registered at ClinicalTrials.gov, NCT00278421., Findings: Between Dec 2, 2005, and Oct 7, 2016, 592 patients were enrolled, of whom 295 patients were randomly assigned to receive six cycles of R-CHOP and 297 were assigned to receive four cycles of R-CHOP plus two doses of rituximab. Four patients in the four-cycles group withdrew informed consent before the start of treatment, so 588 patients were included in the intention-to-treat analysis. After a median follow-up of 66 months (IQR 42-100), 3-year progression-free survival of patients who had four cycles of R-CHOP plus two doses of rituximab was 96% (95% CI 94-99), which was 3% better (lower limit of the one-sided 95% CI for the difference was 0%) than six cycles of R-CHOP, demonstrating the non-inferiority of the four-cycles regimen. 294 haematological and 1036 non-haematological adverse events were documented in the four-cycles group compared with 426 haematological and 1280 non-haematological adverse events in the six-cycles group. Two patients, both in the six-cycles group, died during study therapy., Interpretation: In young patients with aggressive B-cell non-Hodgkin lymphoma and favourable prognosis, four cycles of R-CHOP is non-inferior to six cycles of R-CHOP, with relevant reduction of toxic effects. Thus, chemotherapy can be reduced without compromising outcomes in this population., Funding: Deutsche Krebshilfe., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Optimal treatment for transformed follicular lymphoma (tFL) is not fully defined. Clinical characteristics and treatments that impact on post-transformation outcome of 176 biopsy-proven tFL were analysed. Transformation occurred at initial diagnosis in 52% (Group 1) and after a FL diagnosis in 48% (Group 2). Five-year overall survival was 84% for Group 1 and 51% for Group 2 (P < 0·001). In Group 1, 5-year progression-free survival was superior after rituximab maintenance compared to observation only (94% vs. 53%, P = 0·024). In Group 2, an inverse trend was found between survival and both a higher number of pre-transformation treatment lines and a short time-to-transformation., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Grapevine is a vulnerable crop to several fungal diseases often requiring the use of ethylenebisdithiocarbamate (EBDC) fungicides, such as mancozeb. This fungicide has been reported to have goitrogenic, endocrine disrupting, and possibly immunotoxic effects. The aim of this study was to assess workers' exposure in two scenarios of mancozeb application and analyse the main determinants of exposure in order to better understand their mechanism of influence. Environmental monitoring was performed using a modified Organisation for Economic Co-operation and Development (OECD) "patch" methodology and by hand-wash collection, while mancozeb's metabolite, ethylenethiourea (ETU), was measured in 24-h preexposure and postexposure urine samples. Liquid chromatography-mass spectrometry was used for determination of mancozeb and ETU in different kinds of samples. Closed tractor use resulted in 40 times lower potential exposure compared with open tractor. Coveralls reduced skin exposure 4 and 10 times in case of open and closed tractors, respectively. Gloves used during application resulted in 10 times lower hand exposure in open but increased exposure in closed tractors. This study has demonstrated that exposure to mancozeb is low if safe occupational hygiene procedures are adopted. ETU is confirmed as suitable biological marker of occupational exposure to mancozeb, but the absence of biological exposure limits significantly reduces the possibility to interpret biological monitoring results in occupationally exposed workers.

Treatment of non-Hodgkin lymphoma (NHL) requires chemotherapy regimens with significant risk of febrile neutropenia (FN). For patients at ≥20% FN risk, guidelines recommend primary prophylaxis (PP) with granulocyte-colony stimulating factor (G-CSF). This study assessed whether G-CSF use in NHL was in line with recommendations in routine practice. This was a retrospective, observational study of adult NHL patients receiving first-line (R)CHOP-like chemotherapy and G-CSF support between June 2010 and 2012, in Italy. The primary outcome was whether G-CSF was provided as PP, which was defined as G-CSF initiation on days 1-3 after chemotherapy, ≥3 days' use for daily G-CSFs and continued prophylaxis from cycle 1 across all cycles. Secondary prophylaxis was defined as continued prophylaxis from cycle 2 or later, and all other use was defined as Suboptimal. The analysis included 199 patients, 61% of whom had diffuse large B cell lymphoma and 21% follicular lymphoma. (R)CHOP-21 was given to 52% of patients and (R)CHOP-14 to 32%. Overall, 29% of patients received PP, while two-thirds received Suboptimal G-CSF. Of patients receiving daily G-CSF, 3% received PP and 94% received Suboptimal use; with pegfilgrastim, 65% received PP and 26% Suboptimal use. FN occurred in 13 patients (7%) and grade 3/4 neutropenia in 43%. Chemotherapy dose delays occurred in 22% and dose reductions in 18% of patients. Delivery of G-CSF, particularly daily G-CSFs, was not in accordance with guideline or product label recommendations in a large proportion of NHL patients receiving chemotherapy in Italy.

Purpose: The randomized HD2000 trial compared six cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), four escalated plus two standard cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), and six cycles of COPP-EBV-CAD (cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine, and bleomycin; CEC) in patients with advanced-stage Hodgkin lymphoma. After a median follow-up of 42 months, patients who received BEACOPP were reported to have experienced better progression-free survival (PFS) but not better overall survival (OS) results than those receiving ABVD. We here report a post hoc analysis of this trial after a median follow-up of 10 years., Patients and Methods: Three hundred seven patients were enrolled, 295 of whom were evaluable. At the time of our analysis, the median follow-up for the entire group was 120 months (range, 4 to 169 months)., Results: The 10-year PFS results for the ABVD, BEACOPP, and CEC arms were 69%, 75%, and 76%, respectively; corresponding OS results were 85%, 84%, and 86%. Overall, 13 second malignancies were reported: one in the ABVD arm and six each in the BEACOPP and CEC arms. The cumulative risk of developing second malignancies at 10 years was 0.9%, 6.6%, and 6% with ABVD, BEACOPP, and CEC, respectively; the risk with either BEACOPP or CEC was significantly higher than that reported with ABVD (P = .027 and .02, respectively)., Conclusion: With these mature results, we confirm that patients with advanced Hodgkin lymphoma have similar OS results when treated with ABVD, BEACOPP, or CEC. However, with longer follow-up, we were not able to confirm the superiority of BEACOPP over ABVD in terms of PFS, mainly because of higher mortality rates resulting from second malignancies observed after treatment with BEACOPP and CEC., (© 2015 by American Society of Clinical Oncology.)

Objectives/hypothesis: Altered microRNA expression has been found in many cancer types, including laryngeal squamous cell carcinoma (LSCC). We investigated the association of LSCC-related miR-34c-5p with disease-free survival and overall survival., Study Design: Retrospective cohort study., Methods: Expression levels of miR-34c-5p were detected in 90 LSCC formalin-fixed paraffin-embedded tissues by reverse-transcription quantitative polymerase chain reaction. Overall survival and disease-free survival were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using Cox proportional hazard analysis., Results: A downregulation of miR-34c-5p expression significantly correlated with worse disease-free and overall survival. In the multivariate analysis, low miR-34c-5p expression was associated with an increased risk of recurrence., Conclusions: A downregulation of miR-34c-5p in LSCC is independently associated with unfavorable disease-free survival, suggesting that miR-34c-5p might be a promising marker for evaluating the risk of recurrences., Level of Evidence: NA., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

We conducted a population-based study to establish the outcome of T-cell lymphoma (TCL) patients failing systemic first-line therapy. All TCL patients failing first-line systemic therapy in the province of Modena were identified from Modena Cancer Registry between 1997 and 2010. A total of 53 patients were analysed. Regarding the type of failure, 18 patients relapsed, and 35 progressed during first treatment. Among relapsed patients, the median time from date of response to relapse after first treatment was 6.2 months (range 1.87-102). A total of 18 patients (34%) died before receiving salvage treatment, 21 received platinum or gemcitabine-containing regimens (7 addressed to autologous stem cell transplant (ASCT)), 12 other CT regimens; 2 received radiotherapy (RT). The median survival after relapse (SAR) was 2.5 months. After a median follow-up for living patients after failure of 35 months (range 8-111 months), 44 patients died, and the cause of death was found to be lymphoma progression in all (98%) but one of them. The median SAR was 2.5 months. The 3-year SAR was 19%. Univariate and multivariate Cox regression analyses for SAR were performed. In multivariate analysis, performance status and type of failure were associated with a higher risk of death after relapse. The outcome of TCL patients failing first-line therapy is poor. Only a few cases that could receive ASCT had promising chances of long remission. There is urgent need for novel agents for patients requiring second-line treatment., (Copyright © 2014 John Wiley & Sons, Ltd.)

Brentuximab vedotin (BV) is approved for the treatment of patients with relapsed or refractory CD30-positive Hodgkin lymphoma, and relapsed or refractory systemic anaplastic large-cell lymphoma. Several uncertainties remain regarding the optimal use of the drug in its approved indications as well as outside them. This article reports recommendations on the use of BV issued during a consensus project, sponsored by the Italian Society of Hematology (SIE) and its affiliate societies, Società Italiana di Ematologia Sperimentale (SIES) and Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Scientific evidence on BV was evaluated by a panel of experts, and consensus was developed by group discussion for key questions selected according to the clinical relevance. The following key issues were addressed: testing CD30 positivity to assess eligibility to BV; assessing practice indications of BV in Hodgkin lymphoma and systemic anaplastic large-cell lymphoma; providing pretreatment evaluation of patients candidates to BV; monitoring the response to BV; managing patients treated with BV; and assessing the role of BV in other CD30-positive lymphomas., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To verify whether absolute monocyte count (AMC) and lymphocyte- monocyte ratio (LMR) at diagnosis are valid prognostic parameters in classical Hodgkin lymphoma (cHL)., Patients and Methods: Data were collected from 1450 patients with cHL treated in Israel and Italy from January 1, 1988, through December 31, 2007., Results: The median age of the patients was 33 years (range, 17-72 years), and 70% (1017) of the patients had nodular sclerosis (NS); the median follow-up duration was 87 months. The best cutoff value for AMC was 750 cells/mm(3), and the best ratio for LMR was 2.1. The adverse prognostic impact of an AMC of more than 750 cells/mm(3) was confirmed for the entire cohort, and its clinical significance was particularly evident in patients with NS histology. The progression-free survival (PFS) at 10 years for an AMC of more than 750 cells/mm(3) was 65% (56%-72%), and the PFS at 10 years for an AMC of 750 cells/mm(3) or less was 81% (76%-84%; P<.001). The overall survival (OS) at 10 years for an AMC of more than 750 cells/mm(3) was 78% (70%-85%), and the OS at 10 years for an AMC of 750 cells/mm(3) or less was 88% (84%-90%; P=.01). In multivariate analysis, both AMC and LMR maintained prognostic significance for PFS (hazard ratio [HR], 1.54, P=.006, and HR, 1.50, P=.006) after adjusting for the international prognostic score, whereas the impact on OS was confirmed (HR, 1.56; P=.04) only in patients with NS and an AMC of more than 750 cells/mm(3)., Conclusion: This study confirms that AMC has prognostic value in cHL that is particularly significant in patients with NS subtype histology. This finding links the known impact of macrophages and monocytes in Hodgkin lymphoma with routine clinical practice., (Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objective: To quantify the impact of organized cervical screening programs (OCSPs) on the incidence of invasive cervical cancer (ICC), comparing rates before and after activation of OCSPs., Methods: This population-based investigation, using individual data from cancer registries and OCSPs, included 3557 women diagnosed with ICC at age 25-74years in 1995-2008. The year of full-activation of each OCSP was defined as the year when at least 40% of target women had been invited. Incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs) were calculated as the ratios between age-standardized incidence rates observed in periods after full-activation of OCSPs vs those observed in the preceding quinquennium., Results: ICC incidence rates diminished with time since OCSPs full-activation: after 6-8years, the IRR was 0.75 (95% CI: 0.67-0.85). The reduction was higher for stages IB-IV (IRR=0.68, 95% CI: 0.58-0.80), squamous cell ICCs (IRR=0.74, 95% CI: 0.64-0.84), and particularly evident among women aged 45-74years. Conversely, incidence rates of micro-invasive (stage IA) ICCs increased, though not significantly, among women aged 25-44years (IRR=1.34, 95% CI: 0.91-1.96). Following full-activation of OCSPs, micro-invasive ICCs were mainly and increasingly diagnosed within OCSPs (up to 72%)., Conclusion(s): Within few years from activation, organized screening positively impacted the already low ICC incidence in Italy and favored down-staging., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Follicular lymphoma (FL) patients experience multiple remissions and relapses and commonly receive multiple treatment lines. A crucial question is whether anthracyclines should be used at first-line or whether they would be better "reserved" for relapse and whether FL outcome can be optimized by definite sequences of treatments. Randomized trials can be hardly designed to address this question. In this retrospective multi-institutional study, time-to-next-treatment after first relapse was analyzed in 510 patients who had received either alkylating agents- or anthracycline- or nucleoside analogs-based chemotherapy with/without rituximab at first-line and different second-line therapies. After a median of 42 months, median time-to-next-treatment after relapse was 41 months (CI95%:34-47 months). After adjustment for covariates, first-line anthracycline-based chemotherapy with/without rituximab was associated with better time-to-next-treatment after any salvage than alkylating agents-based chemotherapy with/without rituximab or nucleoside analogs-based chemotherapy with/without rituximab (HR:0.74, P = 0.027). The addition of rituximab to first-line chemotherapy had no significant impact (HR:1.22, P = 0.140). Autologs stem cell transplantation performed better than any other salvage treatment (HR:0.53, P < 0.001). First-line anthracycline-based chemotherapy significantly improved time-to-next-treatment even in patients receiving salvage autologs stem cell transplantation (P = 0.041). This study supports the concept that in FL previous treatments significantly impact on the outcome of subsequent therapies. The outcome of second-line treatments, either with salvage chemoimmunotherapy or with autologs stem cell transplantation, was better when an anthracycline-containing regimen was used at first-line., (© 2014 Wiley Periodicals, Inc.)

Background: Persons living after a cancer diagnosis represent 4% of the whole population in high-income countries. The aim of the study was to provide estimates of indicators of long-term survival and cure for 26 cancer types, presently lacking., Patients and Methods: Data on 818 902 Italian cancer patients diagnosed at age 15-74 years in 1985-2005 were included. Proportions of patients with the same death rates of the general population (cure fractions) and those of prevalent patients who were not at risk of dying as a result of cancer (cure prevalence) were calculated, using validated mixture cure models, by cancer type, sex, and age group. We also estimated complete prevalence, conditional relative survival (CRS), time to reach 5- and 10-year CRS >95%, and proportion of patients living longer than those thresholds., Results: The cure fractions ranged from >90% for patients aged <45 years with thyroid and testis cancers to <10% for liver and pancreatic cancers of all ages. Five- or 10-year CRS >95% were both reached in <10 years by patients with cancers of the stomach, colon-rectum, pancreas, corpus and cervix uteri, brain, and Hodgkin lymphoma. For breast cancer patients, 5- and 10-year CRSs reached >95% after 19 and 25 years, respectively, and in 15 and 18 years for prostate cancer patients. Five-year CRS remained <95% for >25 years after cancer diagnosis in patients with liver and larynx cancers, non-Hodgkin lymphoma, myeloma, and leukaemia. Overall, the cure prevalence was 67% for men and 77% for women. Therefore, 21% of male and 31% of female patients had already reached 5-year CRS >95%, whereas 18% and 25% had reached 10-year CRS >95%., Conclusions: A quarter of Italian cancer patients can be considered cured. This observation has a high potential impact on health planning, clinical practice, and patients' perspective., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)

Background: Risk-reducing mastectomy (RRM) decreases breast cancer (BC) risk in BRCA1/2 mutation carriers by up to 95%, but the Italian attitude towards this procedure is reluctant., Patients and Methods: This is an observational study with retrospective design, using quantitative and qualitative research methods, aimed at evaluating the attitude towards RRM by rapid genetic counselling and testing (RGCT), at the time of BC diagnosis, compared with traditional genetic counselling and testing (TGCT), after previous BC surgery. Secondary aims were to investigate patient satisfaction after RRM and the rate of occult tumour in healthy breasts. A total of 1168 patients were evaluated: 1058 received TGCT, whereas 110 underwent RGCT., Results: In TGCT, among 1058 patients, 209 (19.7%) mutation carriers were identified, with the rate of RRM being 4.7% (10 of 209). Conversely in RGCT, among 110 patients, 36 resulted positive, of which, 15 (41.7%) underwent bilateral mastectomy at the BC surgery time, showing an overall good satisfaction, measured by interpretative phenomenological analysis 12 months after the intervention., Conclusions: Our study shows that RGCT in patients with a hereditary profile is associated with a high rate of RRM at the BC surgery time, this being the pathway offered within a multidisciplinary organization.

In 2003 the Fondazione Italiana Linfomi (FIL) started a clinical research program for investigating initial treatment of frail elderly patients with diffuse large B-cell lymphoma (DLBCL) identified by Comprehensive Geriatric Assessment (CGA). From 2003 to 2006, 334 elderly patients underwent CGA assessment, and 99 patients were classified as frail. Frail patients had a median age of 78 years, stage III-IV disease in 62% and age-adjusted International Prognostic Index (aaIPI) of 2-3 in 53%. Treatment consisted of several different regimens according to physician discretion. After a median follow-up of 36 months, 5-year overall survival (OS) was 28%. In multivariate analysis, aaIPI 2-3 (p = 0.005) and the presence of respiratory comorbidity (p = 0.044) were the only factors that showed independent correlation with OS. Frail patients had a poorer outcome compared with fit patients also if they were treated with rituximab-containing combination chemotherapy (hazard ratio 2.37, 95% confidence interval 1.48-3.78; p < 0.001). CGA is a valid tool to prospectively identify frail subjects among elderly patients with DLBCL.

Background: The analysis of regional lymph nodes is particularly relevant in patients with stage II colorectal cancer, in whom the role of adjuvant chemotherapy remains unclear. The aim of this study was to assess the relationship between number of examined lymph nodes and survival in patients with stage IIA (pT3N0M0) colorectal cancer, and to determine the optimal number of lymph nodes that should be examined., Methods: The study group included all the surgically-treated colorectal cancer patients in stage IIA (n = 657) who were identified through the population-based Cancer Registry of the Province of Modena (Northern Italy), during the period 2002-2006., Results: The median number of harvested lymph nodes was 19 (range 1-68). Considering, as a reference point, patients with 12 or less lymph nodes, subjects with n ≥ 20 lymph nodes examined showed, in univariate analysis, a significantly higher cancer specific (p = 0.01) and relapse-free survival (p = 0.003). The results were confirmed by multivariate analysis (Cox model)., Conclusion: The result suggests that colorectal cancer patients in stage IIA with n ≥ 20 lymph nodes examined exhibit better survival when compared with subjects in whom fewer lymph nodes were examined. The number of 20 lymph nodes is the essential requirement for an oncologic resection of the large bowel.

Purpose: No population-based study has investigated breast cancer (BC) subtypes defined by including Ki67. The aim of this study was to evaluate the relative proportions of immunohistochemical subtypes and differences in relative and disease-free survival between subtypes, in relation to patient and other cancer characteristics in Italian BC patient., Methods: Information on estrogen, progesterone, human epidermal growth factor (HER2), Ki67, and relapses was obtained for 3,381 cases, sampled randomly and anonymously from cases diagnosed in 2003-2005 in nine Italian cancer registries. Relative excess risks (RERs) of death and risks of relapse 5 years after diagnosis were estimated., Results: Luminal A cancers were 42 % of the total, luminal B 27 %, luminal-HER2 14 %, triple-negative 11 %, and HER2-enriched 7 %. For non-metastatic (3,302) cases, 4 and 7 % developed locoregional and distant metastases, respectively. RERs of death and risks of relapse were significantly greater for all cancer subtypes than luminal A, particularly for triple-negative and HER2-enriched cancers, which were more frequent in women <40 years., Conclusions: Our population-based findings confirm that subtype is an independent prognostic factor for BC. Triple-negative and HER2-enriched subtypes would benefit from the development and wide application, respectively, of targeted treatments, which would also improve survival for younger patients.

Objectives: To evaluate screening patterns within organized cervical screening programs (OCSPs) and survival of women with invasive cervical cancer (ICC)., Methods: A population-based study was conducted in Italian areas covered by cancer registries and OCSPs. The study included all women aged 25-65 years diagnosed with ICC between 1995 and 2008, and their screening histories within OCSPs were retrieved. Hazard ratios (HR) of death and 95% confidence intervals (CI) were computed according to screening pattern, using Cox models adjusted for age, ICC stage, and major confounders., Results: Among 3268 women with ICC, 20% were never-invited to OCSP, 36% were never-compliant with OCSP's invitation, 33% were compliant and had a screen-detected ICC within OCSP (i.e., after a positive cytology), and 11% were compliant but had a non-screen-detected ICC. Screen-detected ICCs were more frequently micro-invasive (42%) compared to non-screen-detected ones (14%). Compared to women with screen-detected ICC, the adjusted HRs of death were 1.9 (95% CI 1.5-2.4) for those never-invited, 2.0 (95% CI 1.6-2.5) for never-compliant, and 1.7 (95% CI 1.3-2.4) for compliant women having non-screen-detected ICC., Conclusion: Prolonged survival, beyond down-staging, of women with ICC detected within OCSPs in Italy, further calls for improvements of OCSPs' invitational coverage and participation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Biological markers are crucial factors in order to differentiate female breast cancers and to determine the right therapy. This study aims at evaluating whether testing for biomarkers for female breast cancer has similar frequency and characteristics across and within countries., Methods: Population-based cancer registries of the Association for cancer registration and epidemiology in Romance language countries (GRELL) were asked to complete a questionnaire on biomarkers testing. The data collected referred to invasive female breast cancer cases diagnosed between 2004 and 2009. The investigation focused on 1) the overexpression and amplification of the human epidermal growth factor receptor 2 oncogene (HER2); 2) the expression of oestrogen (ER) and progesterone (PgR) receptors; and 3) the proliferation index (PI). Weighted percentages, the heterogeneity among and within countries, and the correlation between responses and calendar years were evaluated. The study was based on 19,644 breast cancers., Results: Overall, 85.9% of the cases were tested for HER2, 91.8% for both ER and PgR, and 74.1% for proliferative markers. For HER2 and ER-PgR, the frequency of testing increased from 2004 to 2009. Testing varied among countries (HER2 from 82.0% to 95.9%, ER-PgR from 89.3% to 98.9%, PI from 10% to 92%) and also within the same country (e.g. HER2 in Italy from 51% to 99%) as well as within single cancer registries. The most relevant differences were in the scores for positive/negative/not clearly defined HER2 (e.g. HER2 was defined positive if IHC 3+ in 21/33 registries), and in the cut-off of positive cells for ER/PgR (from >0% to >30%) and PI positivity (from >0% to >20%)., Conclusions: Biological markers are widely tested in the Romance language countries; however, the parameters defining their positivity may vary, raising concerns about homogeneity in breast cancer classification and treatment., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The goals of this study were to examine the improvement in quality of life achieved after open surgical treatment of elbow stiffness and to verify the cost/utility ratio of surgery. Thirty-three patients (22 men and 11 women) underwent surgery. The etiologies of elbow stiffness were posttraumatic conditions (n=26), primary osteoarthritis (n=5), and rheumatoid arthritis (n=2). Surgery included 14 ulnohumeral arthroplasties, 6 ulnohumeral arthroplasties associated with radiocapitellar replacement, 5 ulnohumeral arthroplasties associated with radial head replacement, and 8 total elbow arthroplasties. All patients were evaluated pre- and postoperatively with the Mayo Elbow Performance Score, the Mayo Elbow Performance Index, the modified American Shoulder and Elbow Surgeons score, the Quick Disabilities of the Arm, Shoulder and Hand score, and the Short Form 36 after a mean follow-up of 26 months. Possible variables affecting clinical outcome and quality of life improvement were assessed. The cost/utility ratio was evaluated as diagnosis-related group reimbursement per quality-adjusted life year. Mayo Elbow Performance Scores and modified American Shoulder and Elbow Surgeons scores increased, on average, by 43 and 41 points, respectively (P<.0001). Quick Disabilities of the Arm, Shoulder and Hand scores decreased, on average, by 44 points (P<.0001). The improvement in the SF-36 physical and mental component summary score was 7.6 and 7, respectively (P=.0001 and .0018). The cost/utility ratio ranged between 670 and 817 Euro/quality-adjusted life year. A significant correlation was found between pain score and quality of life improvement. An inverse correlation emerged between pre- and postoperative quality of life score. The current study shows that open surgery significantly improves quality of life and elbow function. Selecting the surgical procedure that most effectively reduces pain appears to be the most relevant variable responsible for quality of life improvement. Surgery shows a satisfactory cost/utility ratio, justifying a health spending increase to reduce the social costs resulting from lingering elbow stiffness., (Copyright 2013, SLACK Incorporated.)

Hodgkin lymphoma (HL) is one of the most common types of cancer in the young and one of the most curable forms of cancer. Therefore, there has been an increasing interest in the study of long-term morbidities. The aims of the present study were to evaluate the prevalence and risk factors for impaired gonadal function in a retrospective cohort of 238 HL female survivors from Italy and Brazil and to analyse the role of oral contraceptives (OC) and GnRH-analogues. Besides data collection from HL databases, a specific questionnaire was administered to collect data on gonadal function. The median age at diagnosis was 25 years and the median follow-up was 7 years. Overall, 25% of the patients developed impaired gonadal function. Older age at diagnosis, front-line therapies containing alkylating agents and more than one treatment were independent risk factors, whereas the use of OC or GnRH-a reduced independently the risk of impaired gonadal function. The fertility rate among fertile survivors was low when compared with the general population. We confirmed that older age, type of front-line chemotherapy and a higher number of therapies are associated with gonadal function impairment in terms of infertility and premature menopause in female HL survivors. Also, the use of GnRH-a or OC was independently identified as a protective factor. Further prospective studies are needed to better understand the barriers to parenthood in HL survivors., (Copyright © 2012 John Wiley & Sons, Ltd.)

Aims and Background: This paper aims to provide a comprehensive overview of mid-term epidemiological trends for the major cancer sites in the Emilia-Romagna region of northern Italy (population 4,400,000)., Methods: The MIAMOD method, a back-calculation approach to estimate and project the incidence of chronic diseases from mortality and patient survival, was used for the estimation of incidence and prevalence by calendar year (from 1970 to 2015) and age (from 0 to 99). Survival estimates were taken from cancer registries of northeastern Italy., Results: The estimated incidence of stomach cancer decreased by approximately 75% for both sexes. Trends in incidence of colorectal cancer differed between males and females. For females, the rate increased moderately until the year 2000 with a slow decrease thereafter, whereas the male colorectal cancer incidence showed a regular increase until 2010 followed by a substantial leveling off. Among males the lung cancer incidence and mortality rates showed a steep increase until the late 1980s and a rapid decrease thereafter. Among females, the trends were increasing over the entire study period. The estimated incidence of female breast cancer rose sharply between 1970 and 2001, but from that year onwards a slightly decreasing trend was observed. Mortality peaked in 1988 and has fallen since. The incidence of prostate cancer showed a 3-fold increase. After 2005, the rate is expected to stabilize. Among females, the estimated prevalence increased for breast cancer (52,700 cases expected in 2015), colorectal cancer, lung cancer and melanoma, while decreasing for stomach cancer and cervical cancer. Among males, the estimates showed an upward trend for prostate cancer (32,100 cases expected in 2015) and colorectal cancer, and a leveling off for lung cancer after 2010., Conclusion: The estimates were fairly consistent with previous data from several epidemiological sources. The MIAMOD method provided a picture of the impressive increase in the prevalence of breast cancer and prostate cancer over the 45-year period studied.

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., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The purpose of the work was to investigate the factors predicting early resistance to treatment in Hodgkin lymphoma. Many staging parameters, including relative tumour burden (rTB), were analysed in 246 patients with Hodgkin lymphoma in relation to early failure, that is, less than complete remission (i.e. partial response, null response or progression) or occurrence of early relapse, as clinical expressions of resistance to treatment. Patients with early unfavourable disease were 129 and were treated with four to six cycles of ABVD + involved field radiotherapy; 117 patients with advanced stage disease received six cycles of ABVD + optional irradiation to no more than two sites. The rTB was volumetrically measured through the evaluation of staging computed tomography for all the lesions except bone marrow involvement, which was quantified by calculation. The relationship with early resistance was analysed with logistic regressions. The rTB demonstrated to be the best predictor of early failure in both patient subsets, being superior to the multiparameter International Prognostic Score. The rTB showed a significant exponential relationship with the relative risk of early failure, and with inclusion of the extranodal involvement into the model, a single equation became adequate to predict resistance in both early unfavourable and advanced stage patients. The conclusions are that the rTB is the best pretreatment factor related to the risk of resistance to combined ABVD + radiotherapy and that this relationship can be mathematically expressed in an easy way. A simplified assessment of rTB is highly desirable., (Copyright © 2012 John Wiley & Sons, Ltd.)

Aims and Background: Based on estrogen receptor (ER), progesterone receptor (PgR) and Her2/neu (HER2) expression, four breast cancer subtypes have been distinguished: luminal A (ER and/or PgR/HER2-, Ki67 <14%), luminal B (ER and/or PgR/HER2-, Ki67 ≥14% or ER and/or PgR/HER2), triple-negative (ER-/PgR-/HER2-), and HER2 (ER-/PgR-/HER2). Our aim was to evaluate the prognosis of these phenotypes in the pre-trastuzumab era in a large cohort of Italian women., Methods and Study Design: We studied 2347 breast cancer patients, in stage I-II, registered by the Modena Cancer Registry from 1999 to 2006 in the Modena province, Italy. Overall survival, disease-free survival and second non-mammary tumors were evaluated., Results: A total of 1868 luminal A (79.6%), 195 luminal B (8.3%), 205 triple-negative (8.7%) and 79 HER2 (3.4%) patients were identified. A better prognosis was observed for luminal A than for luminal B, HER2 and triple-negative subtypes (5-year overall survival, 91% vs 89% vs 87% vs 86%, respectively, P <0.001). Disease-free survival for pT1a and pT1b tumors was worse in HER2 (82%) than in triple-negative (90%), luminal B (95%) and luminal A (97%) (P = 0.013). Finally, luminal B patients had a significantly higher rate of second non-mammary tumors than the other groups., Conclusions: In the pre-trastuzumab era, luminal A patients showed a better 5-year overall survival than luminal B, HER2 and triple-negative patients, but in terms of disease-free survival, HER2 subtype represented an unfavorable group over time, whereas the triple-negative group had an increased risk of relapse in the first 42 months and then decreased. Among each prognostic factor, ER <10%, Ki67 >14% and HER2 overexpression are considered as risk factors, but only HER2 positivity seems to preserve the role over time.

Aims and Background: Population-based cancer registry studies of patterns of care can help elucidate reasons for differences in breast cancer survival across Italy documented by previous studies. The aims of the present study were to investigate across-country variation in stage at presentation and standard care for breast cancer cases diagnosed in Italy in the early 2000s., Methods: Samples of adult (≥ 15 years) women with breast cancer diagnosed in 2003-2005 were randomly selected in 9 Italian cancer registries. Logistic regression models were used to estimate the odds of receiving breast-conserving surgery plus radiotherapy (BCS + RT) in each cancer registry, age group, and disease stage category compared with the entire sample (reference); the z test was used to evaluate differences in proportions of stage at diagnosis, employment of chemotherapy in node-positive (N+) disease, and use of endocrine treatment in estrogen-receptor positive (ER+) and negative (ER-) tumors across Italy., Results: Stage at diagnosis was earlier in northern/central registries than in southern areas. Compared with the reference, the odds of receiving BCS + RT was significantly lower in Trapani, Sassari and Naples (southern Italy) after adjusting for age and stage at diagnosis. Among N+ patients, 73% received adjuvant chemotherapy (range, 51% [Biella, northern Italy] to 87% [Ragusa, southern Italy]). Eighty percent of ER+ cancers (range, 50% [Biella, northern Italy] to 97% [Ragusa, southern Italy]) and 18% of ER- cancers (range, 6% [Modena, northern Italy] to 28% [Umbria, central Italy]) were treated with hormonal therapy., Conclusions: Disparities in stage distributions and conservative surgery in breast cancer persist across Italy. On a positive note, we found lower variations in the use of systemic treatment between Italian regions.

Indolent non-follicular non-Hodgkin lymphomas (INFL) are a heterogeneous subset whose treatment has been poorly investigated. In this context we have evaluated the efficacy and safety of combined fludarabine and cyclophosphamide (FC) upfront therapy. Sixty-three patients with advanced INFL were enrolled in the study. Therapy consisted in FC combination (25 and 250 mg/m(2), i.v., respectively, for three consecutive days) every 28 days for six courses. After histological review, 61 patients (36 men, median age 64 years, range 40-70 years) were evaluated (22 small lymphocytic, 11 lymphoplasmacytic, 25 marginal zone and 3 CD5-negative non-Hodgkin lymphomas not otherwise specified). Further two patients were excluded for lack of essential data; six patients were withdrawn before the third cycle because of WHO grade III and IV toxicity. At the final evaluation, the overall response rate was 83% with 40.7% of complete remission. Intention-to-treat analysis showed that at the median follow-up of 36 months, overall survival, progression-free survival and failure-free survival were respectively 78%, 60% and 46%; remission duration among the 49 patients achieving complete remission/partial remission at the end of treatment was 65% (44-78) without significant differences between the main histotypes. The most frequent grade III and IV toxic events were haematological (neutropaenia 34%, anaemia 18% and thrombocytopaenia 11%) and infectious (10%). FC is effective for advanced untreated INFL. Early deaths and haematological toxicity suggest careful patient selection and monitoring.