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Background: In Italy, the incidence of cutaneous malignant melanoma is two-fold higher in the north than in the south. This gradient might be associated with differences in incidence trends and disease surveillance. We compared the time trends in incidence rates, mortality rates, dermatologic office visit rates and skin biopsy rates between the Emilia-Romagna Region (northern Italy) and the Sicily Region (southern Italy).Methods: The cancer registries of Parma, Modena, Ferrara and Romagna (current population, 2,606,465) and Catania-Messina-Enna, Siracusa and Ragusa (2,775,019) provided incidence and mortality records for the years 2008-2017. The records of outpatient services delivered in public health facilities were obtained from the two Regional Administrations. Trends in rates were assessed with the estimated average annual percent change. North-south differences were expressed as age-standardised rate ratios.Results: In the context of a generalised increasing incidence trend, which was more moderate in the female population of the Sicily Region, the standardised rate ratios were: 5.31 (males) and 5.20 (females) for in situ cutaneous malignant melanoma; 2.10 and 2.07 for invasive cutaneous malignant melanoma, with an excess incidence concentrated in lesions ⩽1.00 mm thick (3.58 and 3.05); 3.00 and 2.44 for dermatologic office visits; and 5.25 and 5.02 for skin biopsies. Mortality was stable in both Regions.Conclusions: In the Emilia-Romagna Region, as compared with the Sicily Region, a higher incidence of cutaneous malignant melanoma –especially of in situ and early invasive cutaneous malignant melanoma– coexisted with a higher level of clinical surveillance. The question of the direction of the cause-effect relationship between increased incidence and increased diagnostic scrutiny remains open.

Metabolomics has emerged as a promising discipline in pharmaceuticals and preventive healthcare. However, analysing large metabolomics datasets remains challenging due to limited and incompletely annotated biological pathways. To address this limitation, we recently proposed training machine learning classifiers on molecular fingerprints of metabolites to predict their responses under specific conditions and analysing feature importance to identify key chemical configurations, providing insights into the affected biological processes. This study extends our previous research by evaluating various metabolite structural representations, including Morgan fingerprint and its variants, graph-based structural encodings and proposing novel representations to improve resolution and interpretability of the state-of-the-art approaches. These structural encodings were evaluated on mass spectrometry metabolomic data for a cellular model of the genetic disease Ataxia Telangiectasia. The study found that machine learning classifiers trained on the new representations improved in classification accuracy and interpretability. Notably, models trained on graph-based encoding do not exhibit performance gains, not even with pre-training on a larger metabolite dataset, underlining the efficacy of our proposed representations. Finally, feature importance analysis across different encoding methods consistently identifies similar structures as relevant for classification, underscoring the robustness of our approach across diverse structural representations.

Decentralised systems have been proved to be quite effective to allow for trusted and accountable data sharing, without the need to resort to a centralised party that collects all the information. While complete decentralisation provides important advantages in terms of data sovereignty, absence of bottlenecks and reliability, it also adds some issues concerned with efficient data lookup and the possibility to implement complex queries without reintroducing centralised components. In this paper, we describe a system that copes with these issues, thanks to a multi‐layer lookup scheme based on Distributed Hash Tables that allows for multiple keyword‐based searches. The service of peer nodes participating in this discovery service is controlled and rewarded for their contribution. Moreover, the governance of this process is completely automated through the use of smart contracts, thus building a Decentralised Autonomous Organization (DAO). Finally, we present a use case where road hazards are collected in order to test the goodness of our system for geodata retrieval. Then, we show results from a performance evaluation that confirm the viability of the proposal.

Patients with advanced hepatocellular carcinoma (HCC) and macrovascular invasion (MVI) have dismal prognosis and are referred to systemic treatment or palliation. To investigate the outcomes of patients with HCC and MVI undergoing the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure. Demographics and operative data were retrospectively reviewed. All types of hepatectomies and all types of ALPPS modifications were included. MVI was categorized according to the Japanese Liver Cancer Study Group classification. 28 patients were included. Viral aetiology was the most common cause of chronic liver disease (89.3%). 85.7% of patients were cirrhotic, with a median MELD score of 9 (7–10). MVI of the hepatic veins or inferior vena cava was diagnosed in 46.4% of patients while portal vein involvement was present in 64.2% of cases. Four patients (14.2%) were diagnosed with bile duct involvement. No patients died after Step 1 while complications occurred in 21.4% of cases. Following step 2, 3 patients (11.5%) died and 20 (69.2%) developed complications. Grade B and C post-hepatectomy liver failure occurred in 57.6% and 11.5% of patients, respectively. After a median follow-up of 18 months (7–35), median survival was 22 months (3–40). Eleven patients (39.3%) recurred. Median disease-free survival was 15 months (5–26). The ALPPS procedure is an extreme rescue approach in otherwise inoperable advanced HCC with MVI. The procedure is associated with high morbidity and mortality and patients’ selection is pivotal. Oncological outcomes are safe and should be further investigated.

Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0–14 years) and adults (aged 15–99 years) diagnosed with a haematological malignancy during 2000–14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0–24 years).

Since the Coronavirus disease-19(COVID-19) pandemic, the healthcare systems are reallocating their medical resources, with consequent narrowed access to elective surgery for benign conditions such as gallstone disease(GD). This survey represents an overview of the current policies regarding the surgical management of patients with GD during the COVID-19 pandemic.

In shaping the Internet of Money, the application of blockchain and distributed ledger technologies (DLTs) to the financial sector triggered regulatory concerns. Notably, while the user anonymity enabled in this field may safeguard privacy and data protection, the lack of identifiability hinders accountability and challenges the fight against money laundering and the financing of terrorism and proliferation (AML/CFT). As law enforcement agencies and the private sector apply forensics to track crypto transfers across ecosystems that are socio-technical in nature, this paper focuses on the growing relevance of these techniques in a domain where their deployment impacts the traits and evolution of the sphere. In particular, this work offers contextualized insights into the application of methods of machine learning and transaction graph analysis. Namely, it analyzes a real-world dataset of Bitcoin transactions represented as a directed graph network through various techniques. The modeling of blockchain transactions as a complex network suggests that the use of graph-based data analysis methods can help classify transactions and identify illicit ones. Indeed, this work shows that the neural network types known as Graph Convolutional Networks (GCN) and Graph Attention Networks (GAT) are a promising AML/CFT solution. Notably, in this scenario GCN outperform other classic approaches and GAT are applied for the first time to detect anomalies in Bitcoin. Ultimately, the paper upholds the value of public–private synergies to devise forensic strategies conscious of the spirit of explainability and data openness.

The aim of this study was to analyse the impact of socioeconomic status (SES) on the prognosis of patients with invasive malignant melanoma (MM) incident from 1991 to 2011 in the province of Ferrara, northern Italy. A total of 750 patients provided by the Area Vasta Emilia Centrale Cancer Registry were included in this retrospective cohort study. Prognosis was analysed in terms of overall survival and specific survival. The study determinants were the patients’ SES and district of residence. The confounding effect of sex, age, period and TNM stage at diagnosis was evaluated. In the study population, neither overall survival nor specific survival showed significant differences among different layers of SES and districts of residence. The risk for death from MM was lower for the female sex [hazard risk (HR)=0.68, 95% confidence interval (CI): 0.50–0.94] and for diagnoses made in the most recent period (2005–2011: HR=0.56, 95% CI: 0.36–0.89 with respect to 1991–1997). A worse prognosis was observed in patients older than 70 years at the time of diagnosis (HR=2.33, 95% CI: 1.39–3.91 with respect to the <40-year age group) and in patients with more than pT1 tumours (up to 20 times for pT4 tumours). SES and district of residence did not constitute prognostic factors for MM patients residing in the province of Ferrara. Homogeneity in MM staging, treatment and follow-up strategies due to the relatively small extent of the study area and the presence of a single university hospital of reference, as well as less marked social and economic differences among the study patients in comparison with other previously analysed populations, may account for this finding.

This paper presents the performance assessment study of the PET component of the IRIS PET/CT according to the National Electrical Manufacturers Association NU 4-2008 standard. The IRIS PET/CT is a high-resolution integrated system for PET and CT imaging of small animals. We evaluated the performance of the PET system, carrying out the following measures: spatial resolution, sensitivity, counting rate capabilities, and image quality parameters. Furthermore, two examples of in vivo experiments are shown. The average energy resolution for a whole module is 14% at 511 keV. The maximum absolute sensitivity for a point source at the center of the field-of-view is 8.0 ± 1.1% for 250-750 keV energy window and 6.6 ± 1.0% for 350-750 keV. The scatter fraction for mouse-like and rat-like phantoms are 15.6% (250-750 keV) and 22.4% (350-750 keV), respectively. Recovery coefficients were measured with the image-quality phantom, providing good results with an image uniformity of 7%. The imaging performance of the IRIS PET are confirmed in the animal experiments. With the IRIS PET/CT, it was possible to derive the time activity curve for various regions of interest with time frame duration down to 5 s, thus enabling the possibility to derive the tracer input function.

Preliminary series have shown the feasibility of combined laparoscopic resection of colorectal cancer (CRC) and synchronous colorectal liver metastases (SCRLM). The aim of this study was to compare the short- and long-term outcomes for matched patients undergoing combined resections. An international multicenter database of 142 patients that underwent combined laparoscopic resection of CRC and SCRLM between 1997 and 2013 was compared to a database of 241 patients treated by open during the same period. Comparison of short- and long-term outcomes was performed after propensity score adjustment. After matching, 89 patients were compared in each group including mostly ASA I–II patients, presenting with mean number of 1.5 CRLM, with a mean diameter of 30 mm, and resectable by a wedge resection or a left lateral sectionectomy. A rectal resection was required in 46 and 43 % of laparoscopic and open procedures, respectively (p= 0.65). There was no difference in global operative time, blood loss and transfusion rates between the two groups. A conversion was required in 7 % of the laparoscopic procedures. Morbidity rates were similar in the two groups (p= 1.0). The 3-year overall survival in the laparoscopy and open groups were 78 and 65 %, respectively (p= 0.17). In patients without severe comorbidities presenting with one, small (≤3 cm), CRLM resectable by a wedge resection or a left lateral sectionectomy, combined laparoscopic resection of CRC and SCRLM allowed similar short- and long-term outcomes compared with the open approach.

Aims and background This paper aims to provide a comprehensive overview of midterm 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.

Aims and background The project Surveillance of rare cancers in Italy (RITA) provides, for the first time, estimates of the burden of rare cancers in Italy based on the list of rare cancers proposed in collaboration with the European project Surveillance of Rare Cancers in Europe (RARECARE).Methods RITA analyzed data from Italian population-based cancer registries (CR). The period of diagnosis was 1988 to 2002, and vital status information was available up to December 31, 2003. Incidence rates were estimated for the period 1995–2002, survival for the years 2000–2002 (with the period method of Brenner), and complete prevalence at January 1, 2003.Results Rare cancers are those with an incidence <6/100,000/year. In Italy, every year there are 60,000 new diagnoses of rare cancers corresponding to 15% of all new cancer diagnoses. Five-year relative survival was on the average worse for rare cancers (53%) than for common cancers (73%). A total of 770,000 patients were living in Italy in 2008 with a diagnosis of a rare cancer, 22% of the total cancer prevalence.Conclusions Our estimates constitute a useful base for further research and support the idea that rare cancers are a public health problem that deserves attention. Centers of expertise for rare cancers that pool cases, expertise and resources could ensure an adequate clinical management for these diseases. Our data also showed that cancer registries are suitable sources of data to estimate incidence, prevalence and survival for rare cancers and should continue to monitoring rare cancers in Italy.

Aim To evaluate seasonality in the diagnosis of cutaneous melanoma in Italy.Methods A total of 16,284 invasive (and 1,235 in situ) cutaneous melanomas incident from 1978 to 2002 in 14 cancer registries belonging to the Italian Network of Cancer Registries (AIRTUM) was analyzed. We used the Walter and Elwood test to evaluate seasonality. The monthly distribution of diagnosis was evaluated for sex, skin site, melanoma morphology and period of diagnosis.Results The overall monthly diagnosis of invasive melanoma showed a statistically significant excess around the month of June. The same pattern was present for males and females, across age-groups and periods of time. All skin sites showed a cycling trend, melanoma of the head and neck peaked around April, all the others peaked around June. As regards morphologic types, a cyclic trend was evident for superficial-spreading melanomas (peak around July), for not-specified melanomas (June) and for other histotypes (June). Diagnosis of in situmelanoma peaked in September.Conclusions The present study showed that also in Italy melanoma diagnosis has a seasonal trend, with the peak in early summer. It seemed that summer UV exposure, acting both as a late promoter of malignant melanoma development and also increasing the visibility of pigmented skin lesion, may be relevant to explain such a peak.

Dialectically sharing knowledge everywhere, every time and, above all, very fast — as it is nowadays possible — has revealed the existence and importance of a common, distributed intelligence growing with the contribution of many individuals (a community). The iterating refinement of any information resource by a wider and wider community of sharers leads to undoubted advantages on the final quality and effectiveness of use of this information. Following this path and focusing on the e-learning field, we present a novel system, termed LAUGH, for the cooperative creation and sharing of SMIL-based multimedia resources. Such a system allows users (typically learners and teachers) to enrich the didactical material made available to the learning community. Specifically, they can add captions/subtitles and alternative annotations to the original multimedia contents by resorting to a Wiki-type interface. This open process promotes students' participation, data decentralization, assemblage from diverse sources, sharing of knowledge as well as an improvement to the efficacy of e-learning materials. Throughout the paper, we will meticulously show that LAUGH extends and improves the functionalities provided by the SMIL standard. This motivates the title of this article.

Aims and background The study aimed to validate model-based incidence estimates by means of observed incidence rates provided by Italian cancer registries, for five major cancer sites (stomach, colon and rectum, lung, breast and prostate cancers) and for all cancers together.Methods Recent incidence rates observed by Italian population-based cancer registries were extracted from the data base of the Italian Association of Cancer Registries. Regional estimates of incidence rates for the same cancers were obtained by the MIAMOD method. Observed and estimated crude incidence rates and incidence trends were compared for the period of diagnosis 1985-2000. Eight Italian cancer registries and seven regions were selected for the analysis since they had incidence data available during the entire selected period.Results and conclusions An excellent agreement between estimated and observed crude incidence rates was found for all single cancer sites, regarding absolute incidence levels and time trends. A partial exception was breast, where empirical data showed a sudden increase in the last three years of observation, perhaps due to organized screenings in some Italian regions, and not captured by statistical models. Substantial underestimation of model-based incidence rates was found for all cancers combined, where the difference tended to increase with calendar year, up to a maximum of 20% in recent years. The greatest part of the discrepancy can be attributed to multiple cancers, which were included in cancer registries statistics but were not accounted for in MIAMOD estimates.

Excess of incidence rates is the expected consequence of service screening. The aim of this paper is to estimate the quota attributable to overdiagnosis in the breast cancer screening programmes in Northern and Central Italy. All patients with breast cancer diagnosed between 50 and 74 years who were resident in screening areas in the six years before and five years after the start of the screening programme were included. We calculated a corrected-for-lead-time number of observed cases for each calendar year. The number of observed incident cases was reduced by the number of screen-detected cases in that year and incremented by the estimated number of screen-detected cases that would have arisen clinically in that year. In total we included 13,519 and 13,999 breast cancer cases diagnosed in the pre-screening and screening years, respectively. In total, the excess ratio of observed to predicted in situand invasive cases was 36.2%. After correction for lead time the excess ratio was 4.6% (95% confidence interval 2 to 7%) and for invasive cases only it was 3.2% (95% confidence interval 1 to 6%). The remaining excess of cancers after individual correction for lead time was lower than 5%.

Methotrexate (MTX) represents the antirheumatic drug mainly used in rheumatoid arthritis (RA). HLA-G antigens are inducible nonclassical major histocompatibility complex class Ib molecules important for maintaining anti-inflammatory conditions. The HLA-G gene is characterized by a deletioninsertion polymorphism of 14 bp that controls specific mRNA stability and protein levels. It has been reported that MTX therapy mediates an increase of interleukin-10-producing cells. This cytokine up-regulates HLA-G expression. For this, we tested the hypothesis of an MTX-mediated HLA-G production and the possible relationship with the HLA-G 14-bp polymorphism.

Aims and background To provide model-based estimates of all cancers patient survival in Italy and in Italian large geographical areas (North-West, North-East, Center, South), where only partial coverage of cancer registries data is available, and to describe them in terms of time trends. Moreover, to measure the degree of representativeness of cancer patient survival obtained from Italian cancer registries data.Methods Relative survival in the four main Italian geographical areas was estimated by a parametric mixture model belonging to the class of “cure” survival models. Data used are from Italian cancer registries, stratified by sex, period of diagnosis and age. The Italian national survival was obtained as a weighted average of these area-specific estimates, with weights proportional to the number of estimated incident cases in every area. The model takes into account also differences in survival temporal trends between the areas.Results Relative survival for all cancers combined in Italian patients diagnosed in 1990-1994 was estimated to be higher in women (53%) than in men (38%) at 5 years from the diagnosis. The survival trend is increasing by period and decreasing creasing by age, both for men and women. The greatest gain in terms of survival was obtained by the elderly, with annual mean growth rates in the period 1978-1994 equal to 3.5% and 3.2% for men and women, respectively. More than 50% of the youngest cancer patients were “cured”, whereas for the elderly this proportion dropped to 15% and 25% for men and women, respectively. The South of Italy had the lowest survival and the North the most pronounced increase.Conclusions The obtained national survival estimates are similar, but not identical, to previously published estimates, in which Italian registries’ data were pooled without any adjustment for geographical representativeness. The four Italian areas have different survival levels and trends, showing variability within the country. The differences in survival between men and women may be explained by the different proportion of lethal cancers. Among males, most cases had a poor prognosis (lung and stomach cancers), whereas among females the largest proportion was made up of curable and less lethal cancers (breast cancer).

Abstract Wireless networking is becoming an increasingly important communication means. Entry points to content delivery networks (e.g. portals) have to cope with the primary necessity of distributing multimedia contents to 3G mobile devices. In this paper we discuss the software architecture of a wireless Internet application we have designed and implemented to support the distribution of Mp3-based songs to 3G UMTS devices. Alongside the operational description of the proposed architecture, efforts have been made to examine the effects that Internet traffic has on the performance of UMTS networks, due to the distribution of Mp3 files by means of our wireless application. The download time measurements we have experimentally obtained show that combining modern 3G mobile network technologies with an appropriate structuring of the wireless Internet application may be very effective for the fast distribution of pre-recorded music to mobile clients.

Objective: To measure stage-specific geographic and time variability of breast cancer in seven Italian areas before the onset of organized screening programs. Methods: All invasive cancers (8689 cases) arising in women aged 40–79 years during the pre-screening period 1985–1997, were considered. Multiple Poisson regression analysis was performed. Results: About 39% of the cases were classified as “early,” 52% as “advanced,” and 9% as “unspecified” stage. Age-adjusted incidence rates showed a significant geographic variation for early but not for advanced cancers (range: 58–103 cases/100,000 and 104–125 cases/100,000, respectively). The result was confirmed in the multiple regression analysis after adjustment for year of diagnosis and age. Early breast cancer risk adjusted for age and registry showed a significant increase over time (+ 3.9% per year for all ages, and + 6.2% per year for age category 50–79). In contrast, a decreasing time trend was observed for advanced cancer of 3 cm or over in women aged less than 60. Conclusions: In our study, early breast cancer incidence varied both by geographic area and time before the commencement of screening. The differences in early-stage incidence may well be related to differences in availability of “spontaneous” mammography. Late-stage incidence decreased over time in younger women and for very advanced cases, but not in the older ones, nor for cancers less than 3 cm. Early detection outside organized screening was only partially efficient in reducing advanced breast cancer incidence. The trend of incidence of advanced disease, as previously proposed, is confirmed to be a valid early indicator of effectiveness of screening.

Issues about commercialization of space have been a growing concern in the past decade for the space community. This paper focuses on the work from a team of 51 students attending the Summer Session Program of the International Space University in Bremen, Germany. CASH 2021 (Commercial Access and Space Habitation) documents a plan that identifies commercial opportunities for space utilization that will extend human presence in space, and will chart the way forward for the next 20 years. The group selected four commercial sectors that show the most promise for the future: tourism, entertainment, space system service, assembly and debris removal, and research and development/production. The content of this document presents the results of their research. Historical activities in each of the commercial sectors are reviewed along with the current market situation. To provide a coherent background for future commercialization possibilities a scenario has been developed. This scenario includes a postulated upon ideal future and includes social, political and economic factors that may affect the space industry over the timeline of the study. The study also presents a roadmap, within the limited optimistic scenario developed, for the successful commercialization of space leading to future human presence in space. A broad range of commercially viable opportunities, not only within the current limits of the International Space Station, but also among the many new developments that are expected by 2021 are discussed.

To compare the presentation and prognosis of non-Hodgkin lymphoma (NHL) in people with AIDS (PWA) and in the general Italian population, a record linkage study was carried out. The fraction of NHLs attributable to HIV/AIDS was also estimated. Information from the National AIDS Registry (RAIDS) was linked with records from 13 cancer registries (CR), covering about 15% of the Italian population. During the period 1985–94, among PWA ages 15–49, 136 NHLs were identified (8% of all NHLs) and were compared with 1,481 concurrent incident NHL cases of the same age group among non-PWA. Percentages above 13% of all NHLs were registered in the northern areas of Genoa and Varese, i.e., the most heavily affected by the AIDS epidemic. Between 1 year prior to and 3.5 years after AIDS diagnosis, PWA showed an overall standardised incidence ratio (SIR) for NHL of 302. SIR was particularly high (394) within 3 months after AIDS diagnosis and subsequently declined to 170. SIR was somewhat higher in females (428) than in males (280) but similar among intravenous-drug users (299) and other HIV-transmission groups (309). High-grade NHL, particularly immunoblastic and Burkitt's lymphoma, were twice as frequent among PWA than non-PWA. Conversely, low-grade NHL were less frequent. Except for the high proportion of brain localisation, no clear difference emerged in the pattern of NHL presentation site in PWA compared with non-PWA. At variance with NHL in the general population, among PWA histological grade had little impact on survival, which overall appeared to be very poor (2-year survival: 10%; 95% confidence interval: 3%–17%). Our present linkage of RAIDS and CRs represents an efficient tool for the surveillance of trends in incidence and survival of NHL among PWA in Italy. © 2001 Wiley-Liss, Inc.

The aim of this study was to examine the loss of heterozygosity (LOH) of BRCA1 (17q21) and TP53 (17p13.1) in early-onset breast cancer patients; to correlate biopathological characteristics with molecular alterations; and to investigate the survival of LOH-related cancers.BRCA1 and TP53 LOH were evaluated in 78 early-onset breast cancers (≤40 years, Group 1) and 80 patients with age <55 years (Group 2). Cases were characterized for multiple biological markers (ER, PR, proliferation index (PI), NEU and p53). LOH was carried out on microdissected paraffin embedded tissues; microsatellites D17S855 (BRCA1) and D17S786 (TP53) were amplified by fluorescent PCR and analyzed by an automated DNA sequencer. Early-onset breast cancers showed a higher frequency of ductal histotype (89,7% vs. 56,3% p<0.001), node-positive (53,8% vs. 38,7%), larger size (p=0.017), higher mitotic rate (p=0.025), higher nuclear and final grade (p=0.01 and p=0.001, respectively). D17S855 LOH was 32,8% in group 1 vs. 21% in group 2; D17S786 LOH was 50,7% vs. 31.3% (p=0.03), respectively. BRCA1 LOH was correlated with higher PI (p=0.032) and higher p53 expression (p<0.001) in group 1 and with higher NEU expression (p=0.028) in group 2. TP53 LOH was correlated with p53 overexpression (p=0.03) in group 1. A worse clinical outcome in early-onset LOH related cancers emerged from follow-up data: TP53 and BRCA1 LOH were associated with a shorter relapse free interval (RFI) (p=0.03) and a poorer overall survival (OS) (p=0.04), respectively. This study underlines different biological profiles in the two age groups investigated, probably reflecting different mechanisms of carcinogenesis. In accordance with adverse histopathological features in early-onset patients, LOH-related cancers have an unfavorable prognosis.

Widespread microsatellite instability (MSI) occurs in nearly 15% of sporadic colorectal cancers. Large bowel carcinomas with high-frequency MSI (MSI-H) (instability at ≥ 30% of microsatellite loci) are believed to display distinctive pathologic features and to behave less aggressively than microsatellite-stable (MSS) tumors and carcinomas with low-frequency MSI (MSI-L) (instability at &lt; 30% of microsatellite loci). The aim of the current study was to accurately define the clinicopathologic and biologic features of MSI-H sporadic colorectal carcinomas. MSI status was evaluated in 216 large bowel adenocarcinomas using polymerase chain reaction (PCR) and 6 microsatellite markers. Tumors that showed instability with at least two microsatellite markers were classified as MSI-H, whereas the other tumors were classified as MSI-L (instability at one locus) or MSS (no instability). Expression of p53, hMLH1, and hMSH2 gene products was determined by immunohistochemistry, and DNA ploidy pattern was determined by flow cytometry. The prognostic significance of MSI status was assessed by univariate and multivariate survival analyses. The significantly different pathologic features of MSI-H carcinomas were proximal location; large size; mucinous and medullary histotype; poor differentiation; expanding pattern of growth; more frequent Crohn-like conspicuous lymphoid reaction; and low incidence of extramural vein invasion. Most MSI-H tumors were DNA diploid (33 of 40 tumors; 82.5%) and p53 negative (34 of 44 tumors; 77.3%). Conversely, DNA aneuploidy and p53 overexpression were observed in 82.3% (130 of 158 tumors; P &lt; 0.0001) and 54.1% (93 of 172 tumors; P = 0.0002) of MSI-L/MSS tumors, respectively. Loss of hMLH1 or hMSH2 expression was detected in a high fraction of MSI-H carcinomas (86.0%). Patients with MSI-H tumors showed a better clinical outcome than patients with MSI-L/MSS tumors (P = 0.0017). Furthermore, in multivariate analysis that included conventional clinicopathologic parameters, MSI status, and p53 expression as covariates, MSI status was a significant independent prognostic indicator of disease specific survival. Assessment of MSI status is an essential step in the genetic characterization of large bowel carcinomas and identifies a subset of tumors with distinct clinical, pathologic, and biologic features. Cancer 2000;89:2025–37. © 2000 American Cancer Society.

c-erbB-2 Protein expression was investigated in a series of fifty primary breast cancers by means of a specific monoclonal antibody and immunocytochemistry. Specific staining was observed at the plasma membrane level of neoplastic cells, according to the reported localization of c-erbB-2 protein. Sixty-four percent of tumors scored positive, with a variable amount of stained cells. The rate of protein expression was found to exceed the reported gene amplification. No relationship was observed between c-erbB-2 protein staining and age, meno pausal status or histologic subtypes. An inverse association was found between c'erbB-2 protein staining and estrogen receptor content of tumors, assayed by immunocytochemistry. A positive relationship was observed between c-erbB-2 protein expression and presence of axillary node metastasis. These findings suggest that c-erbB-2 protein expression is a marker of tumor aggressiveness and that its prognostic power deserves further investigation both in node-positive and node-negative patients.

Background Mortality data have clearly highlighted the province of Ferrara as an area with a particular distribution of tumors strictly related with environmental factors.Methods The project of a tumor registry has been planned for a better description of cancer incidence and for a deeper insight into etiologic factors, considering the typical features of the province from geographic and occupational points of view.Results This study presents the registration results of the first 2 years, in order to verify the quality level of data recruitment and to confirm that observed in previous studies. The population covered by the registry was 151,968 males and 165,835 females, with high representation of the elderly. In this period 2,087 tumors in men and 1,778 in women were observed. Lung cancer reaches one of the highest levels in Italy, according to that observed in Lombardy and Veneto regions and the northern Adriatic coast. Incidence and mortality are, however, significantly higher than in other Emilia-Romagna areas, as pointed out by the registries of Parma, Modena and Forlì. Colon cancer also presents high frequencies in comparison with neighboring areas, whereas non-Hodgkin lymphomas reach the highest level in Italy. Gastric tumors, although well represented in males and females, show lower levels than the high-risk neighboring Romagna region. In women, a low incidence of cervix uteri tumors and high levels of breast cancer have also been observed.Conclusions The distribution of such neoplasms and the differences observed among neighboring areas deserve further analytical studies, with the aim of a better reading of cancer onset and diffusion. The quality of data obtained (about 70% of histocytologic confirmations, and 5% of “final” death-certificate-only cases), appears to reach satisfying levels, considering the starting phase of the registry.

The widespread use of diagnostic breast imaging has yielded an increase in the detection of in situ, microinvasive, and small invasive carcinomas and has provided opportunities to study the earliest stages of breast carcinoma development. The authors of this report analyzed the pathobiologic features of 577 minimal breast carcinomas (MBCs), including in situ carcinomas and invasive carcinomas ≤1 cm, according to the definition given by Hartmann in Cancer (1984;53:681-4). Estrogen and progesterone receptors (ER and PR), proliferation index (PI), and p53 and neu expression were studied by immunohistochemical technique and measured by quantitative image analysis in 99 pure in situ carcinomas (ISCp); in 105 mixed invasive/in situ carcinomas, with a separate analysis of in situ (ISCm) and invasive (ICm) components; and in 373 invasive carcinomas ≤1 cm (IC). Follow-up data were available for 164 invasive carcinomas. A progressive increase in the levels of hormone steroid receptors, from the lowest in ISCm to the highest in IC, was observed (ER, P &lt; 0.001; PR, P = 0.005). Levels of PI and p53 expression were higher in ISCm than in the other categories (PI, P = 0.007; p53, P = 0.046). Overexpression of neu was greater in ICm than in IC (P = 0.013). Younger women (≤40 years) with invasive carcinoma had worse biologic profiles, with lower ER (P &lt; 0.001) and higher PI (P = 0.021), neu (P = 0.008), and p53 (P = 0.040). It was demonstrated clinically that PI and neu were the biologic markers with the highest predictive prognostic values in univariate analysis (PI for recurrence, P &lt; 0.015; neu for recurrence and overall survival, P &lt; 0.001 and P &lt; 0.007, respectively) and in multivariate analysis (neu for recurrence and overall survival, P &lt; 0.007 and P &lt; 0.017, respectively). Biologic phenotypes of MBC can be interpreted as reflecting a dimension of neoplastic progression capacity that is independent of tumor size. This study suggests that biologic markers can be integrated with traditional pathologic indicators for accurate staging of patients. Cancer 1998;83:89-97. © 1998 American Cancer Society.

We assessed the reliability of the immunocytochemical assay of estrogen receptor (ER-ICA) as a marker of clinical outcome. Relapse-free interval (RFI) and overall survival (OS) according to ER-ICA status were retrospectively evaluated on a series of 210 patients who had undergone surgery for primary breast cancer between January 1985 and December 1988. ER assay by the dextran-coated charcoal method (DCC) was also performed in 189 tumors. A significant positive correlation was found between the DCC and ER-ICA assays, with an overall agreement of 79 %. ER-ICA status showed a prognostic predictive power with respect to OS and RFI in the whole series of patients and in the subset of node-positive patients. It was also a marker of outcome with respect to OS in the subsets of node-negative patients and patients with tumors ≤ 2 cm in diameter. Moreover, the predictive value of the ER-ICA assay was higher than that of the DCC assay in the present study. These findings emphasize the clinical usefulness of the ER-ICA assay as a measure for prognosis.

IMPORTANCE: Previous retrospective studies have shown that sarcopenia substantially alters the postoperative and oncological outcomes after liver resection for malignant tumors. However, the evidence is limited to small retrospective studies with heterogeneous results and the lack of standardized measurements of sarcopenia. OBJECTIVE: To investigate the role of sarcopenia as a risk factor associated with 90-day morbidity after liver resection for malignant tumors. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included 234 consecutive patients undergoing liver resection for malignant tumors at San Camillo Forlanini Hospital, Rome, Italy, between June 1, 2018, and December 15, 2019. Muscle mass and strength were assessed using the skeletal muscle index (SMI) on preoperative computed tomographic scans and the handgrip strength test, respectively. Patients were then divided into the following 4 groups: group A (normal muscle mass and strength), group B (reduced muscle strength), group C (reduced muscle mass), and group D (reduced muscle mass and strength). MAIN OUTCOMES AND MEASURES: The primary outcome of the study was 90-day morbidity. The following secondary outcomes were investigated: 90-day mortality, hospital stay, and readmission rate. RESULTS: Sixty-four major and 170 minor hepatectomies were performed in 234 patients (median age, 66.50 [interquartile range, 58.00-74.25] years; 158 men [67.5%]). The median SMI of the entire population was 46.22 (interquartile range, 38.60-58.20) cm/m2. The median handgrip strength was 30.80 (interquartile range, 22.30-36.90) kg. Patients in group D had a statistically significantly higher rate of 90-day morbidity than patients in the other groups (51.5% [35 of 68] vs 38.7% [29 of 75] in group C, 23.1% [3 of 13] in group B, and 6.4% [5 of 78] in group A; P &lt; .001). Compared with patients in the other groups, those in group D had a longer hospital stay (10 days vs 8 days in group C, 9 days in group B, and 6 days in group A; P &lt; .001), and more patients in this group were readmitted to the hospital (8.8% [6 of 68] vs 5.3% [4 of 75] in group C, 7.7% [1 of 13] in group B, and 0% [0 of 78] in group A; P = .02). Sarcopenia, portal hypertension, liver cirrhosis, and biliary reconstruction were independent risk factors associated with 90-day morbidity. CONCLUSIONS AND RELEVANCE: Sarcopenia appears to be associated with adverse outcomes after liver resection for malignant tumors. Both muscle mass measurements on computed tomographic scans and muscle strength assessments with the handgrip strength test should be performed at the first clinical encounter to better classify patients and to minimize the risk of morbidity.

La sleeve gastrectomie (SG) est réalisée en routine par trocart unique dans notre département comme alternative à l’approche laparoscopique conventionnelle. L’objectif de cette étude est de rapporter nos résultats postopératoires précoces et au cours d’un suivi de 3 ans après SG par trocart unique (SGTU).

Although FDG-PET has been demonstrated a powerful prognostic indicator in HL, no data are currently available to define how to adapt therapy to FDG-PET results. Moreover the diffusion of FDG-PET in daily practice outside clinical trials is largely unknown. The aim of this study is to assess the current use of FDG-PET in the general population using data from four cancer registries located in the Emilia Romagna region in Northern Italy.Four Cancer Registries (CR) from northern Italy (Modena, Ferrara, Parma and Reggio Emilia Cancer Registry) were used to identify all patients with HL diagnosed from 2006 to 2008. The population covered by the four CR accounts for 1,825,000 people; ICD-O-3 codes from 96503 to 96673 was used to identify cases. A complete dataset was defined to collect data for each patient including demographic features, stage laboratory and clinical data, treatment modalities, response and follow up. Data were collected by active chart review and, when possible by automatic searches. CT and PET scan were collected at different time points: before treatment start (baseline), at the end of treatment (final) and during treatment (interim) and were coded as positive, negative or “inconclusive” according to local report. Patients with stage I-IIA and those with stage IIB-III-IV were classified as having early or advanced disease, respectively.One hundred and sixty-eight patients with histologically confirmed HL were identified. M/F ratio was 1.02, median age at diagnosis was 43 years(12-92) and B symptoms were present in 36% of cases; 51% of patients had advanced disease. The majority of patients was initially treated with ABVD (78%). At least one PET was performed in 137 patients; 68 patients performed all PET assessments (basal, interim and final), 44 patients performed at least 2 scans, and 25 patients performed only one. In no case interim PET was the only scan to be performed. Overall, 317 PET scans that correspond to an overage of 1.8 scans per patient (2.31 if calculated for patients with at least one PET). Baseline, interim and final PET were performed in 115 (74%), 80 (52%), and 122 (72%) patients, respectively. No significant temporal trends were observed during study period for interim and final PET, while rate of patients with basal PET rose from 69% in 2006 to 84% in 2008 (P for trend = 0.05). Baseline PET was positive in all cases. Interim PET was performed after cycle 2 in almost all cases (89%) and was coded as negative in 63 cases (79%), positive in 12 (15%), and inconclusive in 5 (6%). Patients with early or advanced disease had a rate of positive interim PET of 9% and 19%, respectively. Final PET was coded as negative in 103 patients (84%), positive in 17 (14%) and inconclusive in 3 (2%). Rate of positive final PET was 2%, and 23% for patients with early or advanced disease, respectively.The results of this population based study document the wide use of FDG-PET in the daily practice on patients with HL. Based on these data furhter investigation is warranted to assess the role of FDG-PET in clinical decisions, to avoid the risk of an improper use of this technology.No relevant conflicts of interest to declare.

Abstract 5023