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BACKGROUND 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). METHODS We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0-14 years), adolescents (15-19 years), and young adults (20-24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. FINDINGS 164 563 young people were included in this analysis: 121 328 (73·7%) children, 22 963 (14·0%) adolescents, and 20 272 (12·3%) young adults. In 2010-14, the most common subtypes were lymphoid leukaemia (28 205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010-14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000-14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. INTERPRETATION This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group. FUNDING Children with Cancer UK, the Institut National du Cancer, La Ligue Contre le Cancer, Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, Rossy Family Foundation, US National Cancer Institute, and the American Cancer Society.

The incidence of vulvar squamous cell carcinoma has increased for decades in most Western countries - a trend virtually restricted to women aged50 or 60 years. In southern Europe, conversely, the trends have been insufficiently studied. This article reports a study from Italy.Thirty-eight local cancer registries, currently covering 15,274,070 women, equivalent to 49.2% of the Italian national female population, participated. Invasive cancers registered between 1990 and 2015 with an International Classification of Diseases for Oncology, 3rd revision, topography code C51 and morphology codes compatible with vulvar squamous cell carcinoma (n = 6294) were eligible. Incidence trends were analysed using joinpoint regression models, with calculation of the estimated annual percent change (EAPC), and age-period-cohort models.Total incidence showed a regular and significant decreasing trend (EAPC, -0.96; 95% confidence interval (CI), -1.43 to -0.48). This was entirely accounted for by women aged ≥60 years (EAPC, -1.34; 95% CI, -1.86 to -0.81). For younger women, the EAPC between 1990 and 2012 was 1.20 (95% CI, 0.34 to 2.06) with a non-significant acceleration thereafter. This pattern did not vary substantially in a sensitivity analysis for the effect of geographic area and duration of the registry. The age-period-cohort analysis revealed a risk decrease in cohorts born between 1905 and 1940 and a new increase in cohorts born since 1945.The decreasing trend observed among older women and the resulting decrease in total rate are at variance with reports from most Western countries. Age-period-cohort analysis confirmed a decreasing trend for earliest birth cohorts and an opposite one for recent ones.

(1) Objective: In many Western countries, survival from vulvar squamous cell carcinoma (VSCC) has been stagnating for decades or has increased insufficiently from a clinical perspective. In Italy, previous studies on cancer survival have not taken vulvar cancer into consideration or have pooled patients with vulvar and vaginal cancer. To bridge this knowledge gap, we report the trend in survival from vulvar cancer between 1990 and 2015. (2) Methods: Thirty-eight local cancer registries covering 49% of the national female population contributed the records of 6274 patients. Study endpoints included 1- and 2-year net survival (NS) calculated using the Pohar-Perme estimator and 5-year NS conditional on having survived two years (5|2-year CNS). The significance of survival trends was assessed with the Wald test on the coefficient of the period of diagnosis, entered as a continuous regressor in a Poisson regression model. (3) Results: The median patient age was stable at 76 years. One-year NS decreased from 83.9% in 1990–2001 to 81.9% in 2009–2015 and 2-year NS from 72.2% to 70.5%. Five|2-year CNS increased from 85.7% to 86.7%. These trends were not significant. In the age stratum 70–79 years, a weakly significant decrease in 2-year NS from 71.4% to 65.7% occurred. Multivariate analysis adjusting for age group at diagnosis and geographic area showed an excess risk of death at 5|2-years, of borderline significance, in 2003–2015 versus 1990–2002. (4) Conclusions: One- and 2-year NS and 5|2-year CNS showed no improvements. Current strategies for VSCC control need to be revised both in Italy and at the global level.

Background: The EUROCARE-5 study revealed disparities in childhood cancer survival among European countries, giving rise to important initiatives across Europe to reduce the gap. Extending its representativeness through increased coverage of eastern European countries, the EUROCARE-6 study aimed to update survival progress across countries and years of diagnosis and provide new analytical perspectives on estimates of long-term survival and the cured fraction of patients with childhood cancer. Methods: In this population-based study, we analysed 135 847 children (aged 0–14 years) diagnosed during 2000–13 and followed up to the end of 2014, recruited from 80 population-based cancer registries in 31 European countries. We calculated age-adjusted 5-year survival differences by country and over time using period analysis, for all cancers combined and for major cancer types. We applied a variant of standard mixture cure models for survival data to estimate the cure fraction of patients by childhood cancer and to estimate projected 15-year survival. Findings: 5-year survival for all childhood cancer combined in Europe in 2010–14 was 81% (95% CI 81–82), showing an increase of three percentage points compared with 2004–06. Significant progress over time was observed for almost all cancers. Survival remained stable for osteosarcomas, Ewing sarcoma, Burkitt lymphoma, non-Hodgkin lymphomas, and rhabdomyoscarcomas. For all cancers combined, inequalities still persisted among European countries (with age-adjusted 5-year survival ranging from 71% [95% CI 60–79] to 87% [77–93]). The 15-year survival projection for all patients with childhood cancer diagnosed in 2010–13 was 78%. We estimated the yearly long-term mortality rate due to causes other than the diagnosed cancer to be around 2 per 1000 patients for all childhood cancer combined, but to approach zero for retinoblastoma. The cure fraction for patients with childhood cancer increased over time from 74% (95% CI 73–75) in 1998–2001 to 80% (79–81) in 2010–13. In the latter cohort, the cure fraction rate ranged from 99% (95% CI 74–100) for retinoblastoma to 60% (58–63) for CNS tumours and reached 90% (95% CI 87–93) for lymphoid leukaemia and 70% (67–73) for acute myeloid leukaemia. Interpretation: Childhood cancer survival is increasing over time in Europe but there are still some differences among countries. Regular monitoring of childhood cancer survival and estimation of the cure fraction through population-based registry data are crucial for evaluating advances in paediatric cancer care. Funding: European Commission.

Background: Evidence about late effects in adolescent and young adult (AYA) cancer survivors is scarce. This study assessed the risk of subsequent malignant neoplasms (SMNs) to identify the most common SMNs to be considered in follow-up care. Methods: Population-based cancer registries retrospectively identified first primary tumors (between 1976 and 2013) and SMNs in AYAs (15-39years old at their cancer diagnosis). AYA cancer survivors were those alive at least 5years after their first cancer diagnosis. The excess risk of SMNs was measured as standardized incidence ratios (SIRs) and absolute excess risk together with the cumulative incidence of SMNs. Results: The cohort included 67,692 AYA cancer survivors. The excess risk of developing any SMN (SIR, 1.6; 95% confidence interval, 1.5-1.7) was 60%. The excess risk of SMNs was significantly high for survivors of lymphomas; cancers of the breast, thyroid, female genital tract, digestive organs, gonads, and urinary tract; and melanomas. The cumulative incidence of all SMNs in AYA cancer survivors within 25years of their first cancer diagnosis was approximately 10%. Subsequent tumors contributing to approximately 60% of all SMNs were breast cancer, colorectal cancer, corpus uteri cancer, and ovarian cancer in females and colorectal cancer, bladder cancer, prostate cancer, lung cancer, and lymphomas in males. Conclusions: These results highlight the need to personalize follow-up strategies for AYA cancer survivors.

ObjectiveThis study compared all patients undergoing surgery for colorectal cancer in 20 hospitals of Northern Italy in 2019 versus 2020, in order to evaluate whether COVID-19-related delays in the execution of colorectal cancer screening resulted in more advanced cancers at diagnosis and worse clinical outcomes.DesignA retrospective multicentric cohort analysis of patients who underwent surgery for colorectal cancer in March-December 2019 (2019) versus March-December 2020 (2020). The independent predictors of disease stage (oncologic stage, associated symptoms, clinical T4 stage, metastasis) and postoperative outcome (surgical complications, palliative surgery, 30-day death) were evaluated using logistic regression.ResultsThe sample consisted of 1755 patients operated in 2019, and 1481 in 2020 (both mean ages 69.6 years). The proportions of cancers with symptoms, clinical T4 stage, liver and lung metastases in 2019 and 2020 were, respectively: 80.8% vs 84.5%; 6.2% vs 8.7%; 10.2% vs 10.3%; and 3.0% vs 4.4%. The proportions of surgical complications, palliative surgery, and death in 2019 and 2020 were, respectively: 34.4%vs 31.9%; 5.0% vs 7.5%; and 1.7% vs 2.4%. At multivariate analysis, as compared with 2019, cancers in 2020 were significantly more likely to be symptomatic (Odds Ratio - OR: 1.36, 95% Confidence Interval - CI: 1.09-1.69), in clinical T4 stage (OR: 1.38; 1.03-1.85), with multiple liver metastases (OR: 2.21; 1.24-3.94), but less likely to cause surgical complications (OR: 0.79; 0.68-0.93).ConclusionsColorectal cancer patients who had surgery between March and December 2020 had an increased risk of more advanced disease in terms of associated symptoms, cancer location, clinical T4 stage, and number of liver metastases.SHORT SUMMARY BOXWhat is already known about this subject?A specific search regarding the correlation between colorectal cancer oncologic outcomes and COVID-19 showed a few modeling studies which reported the predictions of the potential impact of the diagnostic delays (due to the reduction of the screening programs) on the survival of patients affected by colorectal cancer. However, no study reported any real-life evidence regarding the correlation between the COVID-19 outbreak and the deteriorations of the oncologic outcomes of patients with colorectal cancer.What are the new findings?The present study showed that patients who had surgery for colorectal cancer between March and December 2020 had an increased risk of more advanced disease in terms of associated symptoms, cancer location, clinical T4 stage, and number of liver metastases, than patients who had surgery between March and December 2019.How might it impact on clinical practice in the foreseeable future?The present study confirmed that the backlogs of the screening programs have had, and probably will have, detrimental effects on the oncologic outcomes of patients affected by colorectal cancer. Increased resources should be placed in order to reactivate and enhance the screening programs, and to reduce the risk of colorectal cancer patients to be diagnosed with advanced cancer in the next future.

Objective To explore psychometrics of the Romanian version of the Hospital Survey on Patient Safety Culture (HSOPS) released by the US Agency for Healthcare Research and Quality in 2004. Material and methods The original US survey with 12 composites and 42 items was translated (back translation method), pre-tested on a few staff and then minimally adjusted. A qualitative cross-sectional study was carried out in units from six hospitals in four Romanian regions, based on the census of medical and non-medical staff (n. 969). Participants completed a paper-based self-administered questionnaire. The main outcome measures were: descriptive statistics, confirmatory factor analysis (CFA), internal reliability and intercorrelations among survey composites. Results Nurses accounted for 67% of respondents, and doctors for 23%. Most work units were surgery (24%) and medical specialties (22%). After individual-level CFA on half of the sample, Staffing and Overall perceptions of patient safety composites were dropped and Feedback & communication about error and Communication openness composite items were aggregated to a single Communication composite. Subsequent CFA on the second half of the sample indicated that the novel composite structure adequately fitted the data: comparative fit index=0.90; root mean square error of approximation=0.06; standardized root mean square residual=0.06. Internal consistency was .0.70 for most composites. Spearman intercorrelations among the patient safety composites at the individual level averaged 0.28. Conclusion Psychometrics of the Romanian version of the HSOPS tested in Romania was acceptable for nine composites with 31 items. Integration of this survey with items more pertinent for Romania is suggested.

Background There is a recognized increased risk for colorectal cancer (CRC) in patients with Crohn’s disease (CD). CD patients with CRC might also show a higher prevalence of synchronous and metachronous cancers. On this basis, current guidelines recommend pan-proctocolectomy (PPC) as a treatment. Aim of this study was to evaluate oncologic outcomes and the actual risk of developing metachronous cancers in CD patients undergoing segmental colectomy (SC) for CRC. Methods All CRC CD patients undergoing surgery in select European and U.S. tertiary referral centres were enrolled. Short and long-term results of SC were compared with those of patients undergoing extended colectomies: total colectomy (TC) and panproctocolectomy (PPC). Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes were postoperative complications, 30 days mortality, re-admission, length of stay, incidence of synchronous and metachronous lesions. Results 91 patients were included: 50 (54%) did not have Crohn’s colitis or had cancer developed in a non-involved segment; cancer developed in inflamed colic segment in 41 (46%). Patients without colitis were more often treated with SC (84%). 62 patients underwent segmental colectomies and 29 extended colectomies (EC): 19 PPC and 10 TC. Patients in the SC group were older (p 0.0429), harboured more metastases at diagnosis (p 0.0219) and were less likely to suffer from CD pancolitis (p 0.0022). Incidence of major complications was comparable in SC (8.6%) vs EC (3.45%) (p 0.06602). There was no perioperative mortality and no difference in specific complications, re-admission or length of stay. 28 patients (30%) suffered disease progression: 22 (35%) after SC and 6 (21%) after EC. Of the 19 cancer related deaths (20%), 16 (25%) were in SC and 3 (10%) in EC groups. There was no difference in unadjusted PFS between SC and EC (0.64 vs 0.79 respectively, Wilcoxon p 0.1029) nor in OS (0.74 vs 0.89, Wilcoxon p 0.1591), after a median follow up of 42 months (55.76 vs 31.13 months respectively). Multivariate analysis confirmed no difference in PFS (HR 1.582, p 0.4964) or OS (HR1 428, p 0.4758). 6 synchronous lesions were found in the 29 patients undergoing EC: 3 low grade dysplasia (10%), 1 high grade dysplasia (3.4%) and 2 preoperatively diagnosed cancers (6.8%). 1 patient (1,61%) developed a metachronous colon cancer of the 62 who had SC and none of the 10 TC. Conclusion CRC in CD is a complex situation and choice of procedure is multifaceted. Incidence of synchronous and metachronous cancers appears much lower than previously described. SC offers similar long-term outcomes to more extensive surgery. Current guidelines for the treatment of CRC in CD patients may need to be reconsidered.

Background Little is known regarding the outcomes of inflammatory bowel disease (IBD) patients who required surgery during the outbreak of Coronavirus disease 19 (COVID-19). This study aimed to compare outcomes of IBD patients undergoing surgery in COVID-19-treatment and COVID-19-free hospitals. Methods Retrospective study involving patients undergoing IBD surgery in seven centres (six COVID-19-treatment hubs and one COVID-free hospital) across 5 European countries during the period of highest reduction of elective activity due to the first peak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Predictive variables of the risk of moderate-to-severe postoperative complications were analysed using logistic regression analysis. Considering the large number of regressors and the risk of over-fitting due to the small number of events, the least absolute shrinkage and selection operator (LASSO) method was used. Results Of the 91 patients (59 males, 64.8%) with Crohn’s disease (54, 59.3%) or ulcerative colitis (37, 40.7%), 66 (72.5%) had surgery in a COVID-19-treatment hospital, while 25 (27.5%) were treated in the COVID-19-free centre. A higher proportion of COVID-19-treatment patients required urgent surgery (48.4% vs 24%, p=0.035), did not discontinue the biologic therapy (15.1% vs. 0%, p=0.039), underwent surgery without a SARS-CoV-2 test (19.7% vs. 0%, p=0.0033), and were admitted to intensive care postoperatively (10.6% vs. 0%, p=0.032). Three patients (4.6%) of the COVID-19-treatment group had a SARS-CoV-2 infection during the hospital course. Use of steroids at surgery (Odds ratio [OR]=4.10, 95% CI 1.14–15.3, p=0.03), presence of comorbidities (OR=3.33, 95% CI 1.08–11, p=0.035), and Crohn’s disease (vs. ulcerative colitis, OR=3.82, 95% CI 1.14–15.4, p=0.028) were associated with risk of moderate-to-severe postoperative complications. The admission to a COVID-19-treatment hospital was not associated with higher risks of complications (OR 2.06, 95% CI 0.54–10.4, p=0.30) Conclusion Although a SARS-CoV-2 infection in the postoperative period represented a concrete risk in IBD patients undergoing surgery in COVID-19-treatment hospitals, the study showed that IBD patients can undergo surgery regardless of the COVID-19-status of the referral centre. The study also showed the lack of standardized practice for IBD patients requiring surgery during the COVID-19 outbreak.

Purpose: Adolescent and young adult (AYA, 15-39 years) cancer survivors (alive at least 5 years after cancer diagnosis) are less studied than younger and older cancer survivors and research on their late effects is limited. To facilitate research on long-term outcomes of AYA cancer survivors, we established, in Italy, a population-based AYA cancer survivors' cohort. This article describes the study design and main characteristics of this cohort. Methods: The cohort derives from population-based cancer registries (CRs). Each CR identified AYA cancer patients retrospectively. Treatment for first primary cancer and all health events from diagnosis to death can be traced through linkage with available health databases, such as hospital discharge records (HDRs), mortality files, and outpatient and pharmaceutical databases. Results: Thirty-four CRs participated to the cohort which overall includes 93,291 AYAs with cancer and 67,692 cancer survivors. First primary cancer distribution in AYA cancer survivors differs by sex and age groups because of the different cancer types diagnosed in AYAs. Almost 78% of AYA cancer survivors have HDRs and 14.8% also pharmaceutical and outpatient databases. Conclusion: This cohort will be used to study, for the first time in Italy, the pattern and excess risk of late effects in AYA cancer survivors. HDRs, outpatient and pharmaceutical databases will be used to define primary treatment to assess its impact on AYA cancer survivors' late effects. This cohort exploiting data sources already available at CRs, minimize the data collection effort and it will contribute to assess the feasibility of using administrative database to study cancer survivors' late effects.

Aims: In Italy, incidence rates of thyroid cancer (TC) are among the highest world- wide with substantial intracountry heterogeneity. The aim of the study was to examine time trends of TC incidence in Italy and to estimate the proportion of TC cases potentially attribut- able to overdiagnosis. Methods: Data on TC cases reported to Italian cancer registries during 1998e2012 aged

Background and aims. The Republic of Moldova is a small ex-soviet country in the Central Eastern European group of states, whose official language is Romanian. In countries with limited resources, quality improvement in healthcare and patient safety are very challenging. This study aims to identify which areas of the patient safety culture (PSC) need prompt intervention. Methods. A cross-sectional study was conducted in three Moldovan healthcare settings, using the Romanian translation of the US Hospital Survey on Patient Safety Culture HSOPSC. Descriptive statistics were carried out, based on the responses from n. 929 staff. Percentages of positive responses (PPRs) by item (41 items) and composite (12 PSC areas) were computed. Results. Most respondents were nurses (53%), followed by doctors (35%). The main work areas were: primary care (27%), medical specialties (20%), gynecology and obstetrics (16%), and general surgery (11%). The highest composite PPRs were for: teamwork within units (80%), feedback & communication about error, organizational learning-continuous improvement and supervisor/manager expectations & actions promoting patient safety (78%), and management support for patient safety (75%). The lowest composites were for: frequency of events reported (57%), non-punitive response to errors (53%), communication openness (51%) and staffing (37%). Conclusion. Our results suggest that staffing issues should be tackled to provide safe care. Staff avoid to openly report adverse events and/or discuss errors, likely because a poor understanding of the potential of these events for learning and because of fear of blame or punitive actions. Future research should check psychometrics of the Romanian version of the HSOPSC applied to Moldovan staff.

Background Inflammatory bowel diseases (IBD) patients are particularly vulnerable to an increased incidence of infections, due to both innate characteristics and prolonged pharmacological therapies as steroids, biologics and antibiotics. Very few data are available in the literature about multidrug-resistant (MDR) infections and previous studies have not taken into account the impact of the surgical treatment on infections. We focused on the identification of risk factors for the development of MDR infections in IBD patients undergoing surgical procedures, we investigated the involved microorganisms, and finally, we proceeded to a costs/complications analysis of the treatment. Methods 472 consecutive, unselected IBD patients (285 Crohn’s disease and 187 ulcerative colitis) undergoing surgery from 2016 to 2018 in our Tertiary Care Centre were divided into three groups: MDR infections, antibiotics sensitive infections (no-MDR) and no infections. Results In 37 CD patients nutritional status (p < 0.0008), preoperative biologics (p < 0.008) and antibiotic therapy (p < 0.001), duration of surgical procedure (p < 0.0001) and preoperative hospitalisation length (p < 0.0001) were risks factors for MDR infection development. In 14 UC patients multidrug-resistant infection was related to age at surgery (p < 0.003), disease duration (p < 0.008), inflammatory/nutritional status (p < 0.04), preoperative antibiotic therapy (p < 0.04), and suture leakage (p < 0,01). In the MDR CD group Gram + cocci (54%) were the most implicated pathogens, with a prevalence of 19% of Enterococcus faecium; while in MDR UC patients Gram – bacilli (59%) were the most involved pathogens, with prevalence of Escherichia coli ESBL+ (47%). The antibiotic therapy cost for the CD group was higher in MDR (3249 €) and no-MDR (924 €) groups vs. non-infected patients (41€). In UC we found higher cost only in the MDR group (1408€ vs. 33€). Conclusion Preoperative risk factors involved in the development of MDR infections in IBD patients undergoing surgery were identified. Some factors, such as nutritional status or preoperative antibiotic therapy, were found to be common between CD and UC patients, while some others were found to be specific for UC or CD. Some of these elements appear to be non-modifiable, while some others are part of the multidisciplinary approach, for which further studies are needed to improve the preoperative ‘patient optimisation’ in order to reduce surgical complications.

Objective The Agency for Healthcare Research and Quality Hospital Survey on Patient Safety Culture (HSOPS) was designed to assess staff views on patient safety culture in hospital. This study examines psychometrics of the Italian translation of the HSOPS for use in territorial prevention facilities. Design After minimal adjustments and pre-test of the Italian version, a qualitative cross-sectional study was carried out. Setting Departments of Prevention (DPs) of four Local Health Authorities in Northern Italy. Participants Census of medical and non-medical staff (n. 479). Intervention Web-based self-administered questionnaire. Main outcome measures Descriptive statistics, internal reliability, Confirmatory Factor Analysis (CFA) and intercorrelations among survey composites. Results Initial CFA of the 12 patient safety culture composites and 42 items included in the original version of the questionnaire revealed that two dimensions (Staffing and Overall Perception of Patient Safety) and nine individual items did not perform well among Italian territorial Prevention staff. After dropping those composites and items, psychometric properties were acceptable (comparative fit index = 0.94; root mean square error of approximation = 0.04; standardized root mean square residual = 0.04). Internal consistency for each remaining composite met or exceeded the criterion 0.70. Intercorrelations were all statistically significant. Conclusions Psychometric analyses provided overall support for 10 of the 12 initial patient safety culture composites and 33 of the 42 initial composite items. Although the original instrument was intended for US Hospitals, the Italian translation of the HSOPS adapted for use in territorial prevention facilities performed adequately in Italian DPs.

Background The association of childhood leukemia with traffic pollution was considered in a number of studies from 1989 onwards, with results not entirely consistent and little information regarding subtypes. Aim of the study We used the data of the Italian SETIL case-control on childhood leukemia to explore the risk by leukemia subtypes associated to exposure to vehicular traffic. Methods We included in the analyses 648 cases of childhood leukemia (565 Acute lymphoblastic–ALL and 80 Acute non lymphoblastic-AnLL) and 980 controls. Information on traffic exposure was collected from questionnaire interviews and from the geocoding of house addresses, for all periods of life of the children. Results We observed an increase in risk for AnLL, and at a lower extent for ALL, with indicators of exposure to traffic pollutants. In particular, the risk was associated to the report of closeness of the house to traffic lights and to the passage of trucks (OR: 1.76; 95% CI 1.03–3.01 for ALL and 6.35; 95% CI 2.59–15.6 for AnLL). The association was shown also in the analyses limited to AML and in the stratified analyses and in respect to the house in different period of life. Conclusions Results from the SETIL study provide some support to the association of traffic related exposure and risk for AnLL, but at a lesser extent for ALL. Our conclusion highlights the need for leukemia type specific analyses in future studies. Results support the need of controlling exposure from traffic pollution, even if knowledge is not complete.

The HYPERCAN is a prospective observational Italian multicentre study started in 2012, structured in two main projects (i.e. Projects A and B) that involve both healthy subjects and cancer patients. The HYPERCAN study aims to assess whether the occurrence of a hypercoagulable state may be predictive of cancer diagnosis in healthy individuals, or may be predictive of disease recurrence, clinical progression and thrombosis in cancer patients. Project A involves two different large cohorts of subjects: The first cohort (Project A-1) consists of 10,000 healthy volunteer blood donors to be enrolled and prospectively follow-up for cancer occurrence, while the second cohort (Project A-2) consists of 25,000 people already enrolled in the framework of the general population-based Moli-Sani study. Project B involves 4,000 adult patients with a confirmed diagnosis of four different cancer types (both limited/resected or metastatic diseases), i.e. non-small cell-lung, gastric, colorectal, and breast cancer, to be enrolled and followed up for 5 years or death. Blood samples from all enrolled subjects are collected at baseline and then at different time intervals according to specific time schedules set up for either normal subjects, or patients with limited cancers, or patients with metastatic cancers. Samples will be analysed for a panel of hemostatic proteins, clotting activation biomarkers, thrombin generation, procoagulant microparticles, and thrombophilic polymorphisms. As of November 2015, 6,189 healthy blood donors have been enrolled in project A-1 and 2,532 cancer patients in project B. Clinical follow-up and biological assays are ongoing. The HYPERCAN study wants to explore in different subset of individuals, affected and non-affected by malignant disease, the relationship between coagulation and cancer. The prospective design and the involvement of a large number of individuals will definitively clarify whether alterations in circulating thrombotic markers may be predictive of cancer diagnosis in an otherwise healthy subject and/or may be prognostic of cancer outcome, or of disease progression/relapse in cancer-affected individuals. Finally, the proposed screening with relatively simple and non-high-cost laboratory tests and the use of easy-obtainable peripheral blood samples add a very relevant translational value to this study.

Rationale, aims and objectives Assuring the best standards of care – in a sustainable way – in chronic diseases as breast cancer is nowadays an important challenge for any health system. The aim of this study was to present the methodology used to define a set of quality indicators, computable from administrative data for the pathway of care of breast cancer, and its application at a population level. Method The cohort of 2007–2009 incident cases of breast cancer was identified through a network of six cancer registers in Northern Italy. Cases of sarcoma and lymphoma, patients with multiple primary cancers and those metastatic at diagnosis were excluded; 9614 women were retained for the analysis. For each indicator, the sub-cohort of women eligible for the diagnostic/therapeutic procedures was identified and calculations were performed through record linkage between the cohort and sources of health information. Data on potential available confounders or prognostic factors were also collected. Results For a few indicators, such as cyto-histological assessment before surgery (62%) and intensive follow-up (79%), deviation from recommendations was evident. Younger patients (≤50 years) more frequently needed a short term re-intervention, while older patients less frequently underwent reconstructive surgery and received palliative care. Several indicators had a great variability across hospitals. In some cases, this heterogeneity appeared to be related to the hospital size, with high-volume hospitals being more compliant to guidelines. Conclusion It is possible to evaluate the quality of cancer care delivered in clinical practice in recent years, in order to implement interventions aimed to improve adherence to international standards of care.

Summary Background : Recurrences after surgery for Crohn's disease are frequent and unpredictable. To date, there is little agreement as to which factors increase a patient risk of early recurrence. Aim : To assess whether the post-operative behaviour of diseased bowel walls, as determined by ultrasound, may be a useful predictor of relapse. Methods : A total of 127 Crohn's disease patients were monitored after surgery by means of bowel ultrasound as well as by clinical and laboratory evaluations for a median follow-up of 41.0 months. Bowel wall thickness of diseased loops measured at ultrasound during follow-up was compared with the presurgery values. Multivariable survival analysis was performed to elucidate predictors of early post-operative recurrence. Receiver operating characteristic curves were also constructed taking into account bowel wall thickness for selecting Crohn's disease patients with high risk of clinical/surgical recurrence. Results : The estimated 5 years survival probability of symptomatic Crohn's disease recurrence were 90% and 33%, respectively for unchanged/worsened bowel wall thickness vs. improved bowel wall thickness at 12 months from surgery. The hazard ratio for unchanged/worsened bowel wall thickness at 12 months was 8.9 (95% CI: 3.4–23.2). Receiver operating characteristic curve identified a bowel wall thickness > 6.0 mm at 12 months from surgery as directly associated with the risk of having a Crohn's disease recurrence (hazard ratio was 6.5, 95% CI: 2.8–15.4). Conclusions : Systematic ultrasound follow-up of diseased bowel walls after conservative surgery allows the early identification of patients at high risk of clinical/surgical recurrence.

Summary Background : Although bowel ultrasound is a widely accepted diagnostic tool in bowel diseases, its value as the primary imaging procedure in patients with symptoms/signs suggestive of inflammatory bowel disorders is still unclear. Aim : To investigate the accuracy of bowel ultrasound compared with barium X-ray studies, computed tomography, endoscopy and bowel surgery in the initial assessment of inflammatory bowel disorders. Methods : Four hundred and eighty-seven patients hospitalized consecutively for symptoms or signs suggestive of a bowel disorder between December 1999 and March 2002 were initially enrolled in the study. All patients underwent bowel ultrasound as the first imaging procedure within 36 h of admission; radiographic evaluations, endoscopy and/or surgery were then performed as appropriate and the results of these investigations were used as the gold standard. Results : Three hundred and thirty-six patients had pathological findings of the bowel detectable at ultrasound as the final diagnosis. The main organic disorders found were Crohn's disease (56%), ulcerative/indeterminate colitis (30%), bowel tumours (5%), appendicitis/diverticulitis (2%) and other inflammatory conditions (8%). The overall sensitivity and specificity of bowel ultrasound were 85% and 95%, respectively, whereas the positive and negative predictive values were 98% and 75%, respectively. Comparisons of ultrasound with X-ray or endoscopic results by disease localization showed that the diagnostic performance of ultrasound was higher for inflammatory conditions of the ileum and sigmoid/descending colon (sensitivity of 92% and 87%, respectively), whereas abnormalities localized in the rectum, duodenum and proximal jejunum were often missed by ultrasound. Conclusions : In expert hands, bowel ultrasound is highly predictive of inflammatory disease localized in the ileum or colon, and may well be used as the primary imaging method when Crohn's disease or ulcerative colitis is suspected on a clinical basis.

Summary Aim : To establish whether intestinal ultrasound, clinical or biochemical indices of activity can assess histological features of ileal stenosis in Crohn's disease. Methods : In 43 patients undergoing surgery for a single ileal stenosis, clinical and biochemical parameters, as well as intestinal ultrasound, were assessed prior to surgery. The echo pattern of thickened bowel segments at the site of stenosis was classified as hypoechoic, stratified or mixed (segments with/without stratification). During surgery, stenoses were identified, resected and then histologically examined using standardized criteria. Results : Clinical and biochemical indices of activity showed an overall weak positive correlation with histological inflammatory parameters and a negative correlation with fibrosis. The intestinal ultrasound echo pattern at the stenosis site was stratified in 25 patients, hypoechoic in 14 and mixed in four. Stenoses characterized by a stratified echo pattern showed a significantly higher degree of fibrosis, those characterized by hypoechoic echo pattern showed a higher degree of inflammation, while stenoses with a mixed echo pattern showed high degrees of both fibrosis and inflammation. Conclusion : Ultrasound and, to a lesser degree, clinical and laboratory indices discriminate between inflammatory and fibrotic ileal stenoses complicating Crohn's disease, thus allowing appropriate medical and/or surgical treatment to be defined.

to present a set of indicators developed from six Local Health Authorities of the Lombardy Region to monitor the diagnostic and therapeutic pathway of breast cancer patients, applied to 2007-2009 incident cases.retrospective cohort study.all subjects with primary breast cancer, incident in the period 2007-2009, and collected by cancer registries of Milano 1, Bergamo, Cremona, Milano, Milano 2 and Monza-Brianza (5,320,272 inhabitants) were included.through the use of combined current health databases (health registry, hospitalizations, outpatient, pharmaceutical prescription and specific database for anticancer drugs), for each incident case 34 different indicators have been developed to measure the appropriateness of the procedures provided for diagnosis, treatment (surgical and medical) and follow-up. For each indicator, we analyzed the relationship with age, stage, deprivation index, type of treatment, volume of the specific procedure of the hospital where primary surgery was performed. Estimates were adjusted using multilevel regression models.12,988 incident cases, without metastatic diseases and other cancers, were included in the cohort: 62% were localized to the breast, 33% to the axillary lymph-nodes, 3% metastatic ab initio, and 2% with unknown stage. Deviations from the expected value of different magnitude depending on the type of indicator were observed: the most important differences were detected for the follow-up indicators. There was, in fact, an excess of several procedures in the first year of follow-up: 75% of the cases performed a dosage of a tumor marker, 67% an ecography or a CT scan or an MR, and 37% a bone scan. On the other hand, the access to neoadjuvant and adjuvant treatments in older women was far below the expected values.the study presents data derived from a large cohort of population cases; the set of indicators was validated by a board of oncologists. The use of indicators calculated by linking the cancer registries (that provide staging) and administrative databases allows the assessment of compliance to the guidelines for diagnosis and treatment of tumours. This experience shows that it is possible to develop a methodology, shared with clinicians, to define indicators that measure the distance between guidelines and current clinical practice in order to decrease variability, to limit inappropriateness, and to reduce unnecessary diagnostic tests for patients (and, consequently, hospitals organizational overload). In order to be sustainable and equitable, a health care system must be able to ensure implementation of protocols/procedures based exclusively on the best available scientific evidences.

Synovial sarcomas (SS) are characterized by a chromosomal translocation t(X;18)(p11.2;q11.2) which usually fuses the SYT gene from chromosome 18 to SSX1 or SSX2 genes on chromosome X. Also, a Variant SYT-SSX4 fusion gene has recently been shown in a single SS case. In addition to these cytogenetic changes, bcl-2 expression, as assessed by immunohistochemistry, has been reported to be an almost general constitutive alteration of SS. In the present work, we analyze a series of 36 SS surgical samples (from 34 patients) by RT-PCR for the presence of the SYT-SSX1 or the SYT-SSX2 fusion transcript. The analysis was extended to SYT-SSX4 on SYT-SSX1-negative and SYT-SSX2-negative cases only. Our results showed a significant correlation between the SYT-SSX2 fusion and the monophasic SS histologic subtype. SYT-SSX1 fusion transcripts were present in both monophasic and biphasic tumors. The SYT-SSX4 fusion type was detected in a single monophasic SS. In the same series of SS cases, we also confirmed and extended the previously reported constitutive expression of bcl-2 protein, by using both immunohistochemical and western blot analysis. Moreover, we demonstrated that the BCL-2 gene is not rearranged or amplified at genomic level, indicating that the high levels of bcl-2 expression observed in SS might result from transcriptional activation of the gene and/or protein stabilization. Finally, we show that bcl-2 is not phosphorylated in tumors from patients who had been preoperatively treated with radio/chemotherapy, in tumors from untreated patients, or in an SS cell line (CME-1) after in vitro treatment with cytotoxic concentrations of DNA-damaging agents or taxanes. These data indicate that SS cells are unable to activate an apoptosis pathway involving bcl-2 phosphorylation/inactivation and may provide a possible explanation for the limited effectiveness of conventional pharmacological treatments of this tumor type.

Fifty-three neuroendocrine lung tumors (24 carcinoids, one atypical carcinoid, five large-cell neuroendocrine carcinomas, and 23 small-cell lung carcinomas) were investigated for immunocytochemical expression of several gene products, i.e., p53, Rb, bcl-2, c-kit, mdm-2, cdk-4, p21 proteins, and proliferation index as assessed by MIB-1. The goal of the study was to explore the relationships between histotypes in light of their own gene product-based immunophenotypical profiles. To this aim we applied the multiple correspondence analysis, which is an exploratory statistical multivariate technique that converts a data matrix into a particular type of graphic display in which the rows and columns are depicted as points. Such statistical analysis displayed that some categories of the gene product-based immunophenotyping variables are grouped in the plot identifying three groups: the first group related to carcinoids, the second to small-cell carcinomas, and the third to large-cell neuroendocrine carcinomas. These data support the evidence that carcinoids and small-cell carcinomas are two distinct, apparently immunogenotypically unrelated entities among neuroendocrine lung tumors and that atypical carcinoids and large-cell neuroendocrine carcinomas seem not to represent intermediate steps between them.

A retrospective search for lymphocytic infiltration of the thyroid was performed on archival paraffin specimens from 95 cases of thyroid medullary carcinoma observed at a single institution during a 30-year period. A mild lymphocytic infiltration of the nonneoplastic thyroid tissue, mainly concentrated at the edge of the tumor mass, was observed in 33 cases, while in a further 24 cases a moderate to marked lymphocytic infiltration, resembling that seen in chronic lymphocytic thyroiditis, was homogeneously distributed all over the gland, with no apparent relationship to the site of the primary tumor. Virtually no lymphocytic infiltration was detected inside of any of the tumors. The presence of chronic lymphocytic thyroiditis seemed to be a characteristic of the host rather than a tumor-induced event. Statistical univariate analysis of relapse-free survival and overall survival showed that lack of chronic lymphocytic thyroiditis marked those patients with an increased risk of disease recurrence and death. However, the observed risk for survival was statistically nonsignificant, whereas that for disease recurrence was significant and remained in a multivariate model of statistical analysis.

Twenty-nine samples from 28 cases of vulvar squamous cell carcinoma, of which 13 fulfilled the criteria of the bowenoid subtype (mean age 45 years, range 31-68) and 16 of the usual subtype of invasive squamous cell carcinoma (ISCC) (mean age 67.5 years, range 34-83) were investigated for human papillomavirus (HPV) DNA, TP53 alterations, and mdm2 and bcl-2 gene product deregulation. Microscopically all the bowenoid subtype cases (group I) showed a high-grade intraepithelial (VIN 3, carcinoma in situ) lesion associated with early invasive carcinoma in six cases and overt invasive carcinoma in one. By contrast, no evidence of early carcinoma was present in the ISCCs (group II). By in situ hybridization and/or Southern blot hybridization or polymerase chain reaction (PCR), HPV DNA was detected in all cases of group I and in four of 16 cases (25%) of group II, two only by Southern blot after PCR. By single-strand conformation polymorphism and immunocytochemistry only wild-type TP53 and absence of detectable p53 product, respectively, were found in all cases of group I, i.e., in high-risk HPV-positive carcinomas, whereas mutations and/or p53 overexpression accounted for 75% in group II, i.e., in mainly HPV-negative carcinomas. The TP53 gene mutations observed in invasive carcinomas were significantly related to node-positive cases (p = 0.04). Taken together and in agreement with in vitro data, these results support the view that an alteration of TP53, gained either by interaction with viral oncoproteins or by somatic mutations, is a crucial event in the pathogenesis of vulvar carcinomas, but that TP53 mutations are mainly associated with disease progression. Finally, a preliminary immunocytochemical analysis seems to speak against the possible involvement of both MDM2 and BCL-2 gene products in the development of vulvar carcinoma.

INTRODUCTION and AIM: The HYPERCAN study is an ongoing prospective Italian multicenter trial, designed to test whether the persistence of a laboratory hypercoagulation abnormalities may predict early cancer diagnosis in healthy subjects (Project A), or prognosis and response to therapy in patients with cancer (Project B). The aim of this abstract is to present a preliminary analysis of data collected for project A. MATERIAL AND METHODS: A large healthy population of Italian blood donors from Bergamo and Milan areas (North Italy) is prospectively enrolled after informed written consent and followed-up for 5 years for the occurrence of cancer. As established by a monitoring schedule, blood donors are periodically screened for a series of serological, biochemical and clinical parameters, and tested for viral infections. We plan to enroll 10,000 donors of both gender, age range 35-65, in 5 years. Blood samples from each study subject are collected at enrollment and after 8-10 months, and processed to obtain plasma, buffy coat, and serum subsamples, which are stored in a dedicated biobank until testing for hypercoagulation biomarkers. Demographic and clinical data are collected, including age, gender, body mass index (BMI), current medications, relevant comorbidities, routine hematological and biochemical workup. In addition, subjects are asked to fill in a questionnaire on lifestyle, smoke and dietary habits. An identification of all malignant tumors, according to the categories 140-208 (International Classification of Diseases) is carried out every 6 months. RESULTS: Between April 2012 and June 2016, 6,607 blood donors (70% males; median age 48 years) have been recruited. Routine biochemical and hematological workups are into the normal range values in more than 90% of subjects. The analysis of questionnaires reveals that 57% of the donors were not smokers, 15% regular smokers, 28% ex-smokers; 49% of them were moderate/low alcohol consumer (≥ 2 drink/die). The crude incidence of all malignant cancers in the Bergamo/Milan area is 552 cases/100,000 persons/year in males and 382 cases/100,000 person/year in females. According to the Cancer Registry, 57 cancer cases (38 males and 19 females) are to be expected in the general population in the age range 35-65 years, after a median follow-up of 2.5 years. In our population, at June 2016, after a median follow-up of 2.5 years, we recorded a total of 46 cancer cases (35 M / 11 F). Five cases were excluded because diagnosis occurred within 6 months from enrollment (incident cancer cases); the remaining 41 cases included in the analysis were diagnosed with cancer 6-28 months from enrollment (median time to diagnosis = 24.8 months). Median age at diagnosis of cancer was 53 years. The most frequent tumor type in male donors was prostate cancer (25.8%), followed by colo-rectal (19.3%) and thyroid (12.9%) cancers. In female donors, breast cancer was the most frequent (40%). Currently, the enrollment of healthy donors and follow-up is ongoing, as well as the identification of new cancer cases. Next, according to the original plan, samples from 3 matched cancer-free donors for each cancer-case donor (cancer: non-cancer = 1:3 ratio) will be analyzed in parallel for hypercoagulation markers. CONCLUSIONS: This preliminary analysis reveals that the distribution of tumor types in our population reflects the same as reported for the general population of the same geographic area. Second, in our population of healthy blood donors, the incidence of cancer diagnosis is lower than that predicted from epidemiological data. This message supports the concept that a healthy lifestyle can be effective to prevent cancer. Project funded by AIRC "5xMILLE" n. 12237 grant from the "Italian Association for Cancer Research (AIRC)". Disclosures Falanga: Pfizer: Speakers Bureau; Aspen: Speakers Bureau; Janssen: Speakers Bureau.

Micro- or macroalbuminuria is associated with increased cardiovascular risk factors among patients with type 2 diabetes, but whether albuminuria within the normal range predicts long-term cardiovascular risk is unknown. We evaluated the relationships between albuminuria and cardiovascular events in 1208 hypertensive, normoalbuminuric patients with type 2 diabetes from the BErgamo NEphrologic Diabetes Complication Trial (BENEDICT), all of whom received angiotensin-converting enzyme inhibitor (ACEI) therapy at the end of the trial and were followed for a median of 9.2 years. The main outcome was time to the first of fatal or nonfatal myocardial infarction; stroke; coronary, carotid, or peripheral artery revascularization; or hospitalization for heart failure. Overall, 189 (15.6%) of the patients experienced a main outcome event (2.14 events/100 patient-years); 24 events were fatal. Albuminuria independently predicted events (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.02-1.08). Second-degree polynomial multivariable analysis showed a continuous nonlinear relationship between albuminuria and events without thresholds. Considering the entire study population, even albuminuria at 1-2 μg/min was significantly associated with increased risk compared with albuminuria

Background: Crohn’s disease (CD) is associated with penetrating complications such as phlegmons and intra-abdominal abscesses. As the management of the patients influenced by the presence of such complications, a readily available tool for the diagnosis of extramural complications in CD is needed. Preliminary findings suggest that the assessment of vascularity within intra-abdominal masses may distinguish between phlegmons and abscesses. Aim of our study was to evaluate the use of contrast enhanced ultrasound (CEUS) to distinguish between phlegmons and intra-abdominal abscesses in CD patients as a point-of-care technique. Methods: From November 2011, consecutive patients with complicated CD were enrolled. Indications of patient assessments by CEUS were symptoms, signs and biochemical exams indicating penetrating behavior (abdominal pain, mass, fever, elevated CRP and leukocytosis). A total of 22 CD pts (14 M; median age 27 yrs, range 18 75; disease duration: median 54 mos, range 1 564; CD site: ileal in 13 pts, ileo-colonic in 9 pts; CD behavior: penetrating in 20 pts, stricturing in 2 pts; previous ileocolonic resection in 9 pts) were included. Clinical evaluation by an IBD expert and other cross sectional imaging techniques (MR and CT) were considered as the standard. Results: CEUS detected abscesses in 9 and phlegmons in 12 pts. One patient had an unspecified lesion that was diagnosed as metastasis by PET. Six out of 9 abscesses were confirmed by CT-Enteroclysis and these pts underwent surgery during the follow up. The remaining 3 pts with abscesses were treated with antibiotics and are still in follow up (17.5 mos). In the phlegmon group, 4 out of 12 patients were evaluated by CT or MRI that confirmed CEUS findings in 3 cases but in one patient a deep abscess was identified and surgery was scheduled. Eight out of 12 pts were clinically followed up (median: 16 mos). Two of these patients developed an abscess after one week from CEUS despite medical treatment. Overall CEUS correctly identified 19 out of 22 lesions (86%) on the basis of cross sectional imaging modalities and clinical follow up used as final diagnosis. Conclusions: CEUS is a non-invasive, radiation free and point-of-care technique able to differentiate phlegmons from abscesses driving a prompt clinical management in complicated CD patients. P255 Computed virtual chromoendoscopy with FICE in the definition of raised dysplastic lesions and pseudopolyps in long-standing ulcerative colitis: a preliminary, prospective, study towards a new classification A. Cassinotti1 *, F. Buffoli2, P. Fociani3, V. Villanacci4, T. Staiano2, M. Fichera1, R. Grassia2, G. Manes1, M. Salemme4, M. Lombardini1, P. Molteni1, G. Sampietro5, D. Foschi5, G. Maconi1, R. de Franchis1, S. Ardizzone1. 1Luigi Sacco University Hospital, Gastroenterology and IBD Unit, Milan, Italy, 2Istituti Ospitalieri Cremona, Endoscopy Unit, Cremona, Italy, 3Luigi Sacco University Hospital, Pathology Unit, Milan, Italy, 4Spedali Civili, Pathology Unit, Brescia, Italy, 5Luigi Sacco University Hospital, General Surgery, Milan, Italy

Background and Aim: Mucosal healing (MH) after short-term medical treatment is being considered as an important step in the therapeutic work-up of inflammatory bowel disorder (IBD) patients due to the potential prognostic role of MH in predicting disease outcome. However, IBD patients are reluctant to be re-endoscoped during follow-up; therefore, there is a need for non-invasive alternative index of MH which can replace endoscopy in clinical practice. We evaluated bowel ultrasound (US) as a surrogate of colonoscopy in a series of consecutive patients with active ulcerative colitis (UC). Patients and Methods: 83 patients with moderate to severe UC requiring high-dose steroids were initially recruited; endoscopic severity of UC was graded 0–3 according to Baron score, and US severity was also graded 0–3 according to the colonic wall thickening and the presence of vascular signal at power Doppler. 74 patients responsive to steroids and then maintained on 5-ASA compounds were followed up with repeated colonoscopy and bowel US at 3, 9 and 15 months from entry. Concordance between clinical, endoscopic and US scores at various visits was determined by kappa statistics. Multiple unconditional logistic regression models were used to assess the predictivity of Truelove, Baron and US scores measured at 3 and 9 months on the development of a UC relapse (Baron score 2–3) at 15 months. Results: An inconsistent concordance was found over time between 0 and I Baron scores and Truelove score (weighted κ between 0.38 and 0.94), with high and consistent concordance between 0 and I Baron scores and US scores (weighted κ between 0.76 and 0.90). On logistic regression analysis, a moderate/severe Baron score, regardless of their Truelove score, at 3 months was associated with a high risk of endoscopic activity at 15 months (OR 5.2; 95% CI: 1.6–17.6); similarly, patients with severe US scores (2–3) at 3 months had a high risk of severe endoscopic activity at 15 months (OR 9.1; 95% CI: 2.5–33.5). Discussion: In expert hands bowel US may be used as a surrogate of colonoscopy in evaluating the response to high-dose steroids in severe forms of UC. US score after 3 months of steroid therapy accurately predicts clinical outcome of disease at 15 months.

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Objective. To determine the prevalence of cytomegalovirus infection in patients with steroid-refractory ulcerative colitis who required colonic resection, and to assess its possible association with the use of immunosuppressive and steroid treatment and outcome after colectomy. Patients and methods. The study included surgical specimens and related pre-operative endoscopic biopsy specimens of 77 consecutive ulcerative colitis patients (34 females) who underwent colectomy because of intractable steroid-refractory ulcerative colitis (55 patients), toxic megacolon (6 patients), dysplasia or cancer (7 patients) or loss of function of the colon (9 patients). Clinical features and current and past treatments were analysed. Haematoxylin and eosin and specific immunohistochemical staining for cytomegalovirus were used to detect inclusion bodies in all specimens. Results. Cytomegalovirus infection was found in 15 of 55 steroid-refractory ulcerative colitis patients (27.3%) and in 2 of 22 non-refractory patients (9.1%) (p = 0.123). Only six patients had positive staining for cytomegalovirus in pre-operative endoscopic biopsy specimens. Detection of cytomegalovirus inclusion in biopsy specimens was not related to the number of biopsies or to time that had elapsed since colonoscopy and index surgery. Cytomegalovirus-positive patients were more likely to be on systemic corticosteroids (p = 0.03). In contrast, current use and duration of immunosuppressive treatment, number of steroid cycles since diagnosis and in the last year, as well as chronic use of steroid in the last year were not significantly related to cytomegalovirus infection. Cytomegalovirus-positive patients did not receive antiviral therapy following proctocolectomy but did not show endoscopic or histological cytomegalovirus reactivation in the ileo-anal pouch and in the remaining bowel. Conclusions. Cytomegalovirus infection is frequently found in surgical specimens of patients with steroid-refractory ulcerative colitis and is more likely in patients on corticosteroid treatment. Cytomegalovirus infection is frequently unrecognised in pre-operative biopsy specimens, thus raising concerns about the accuracy of the available diagnostic tools. Unrecognised and untreated cytomegalovirus infection does not affect the outcome of ulcerative colitis patients following proctocolectomy.