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Background: The Southeast European (SEE) region of 10 countries and about 43 million people differs from Western Europe in that most SEE countries lack active cancer registries and have fewer diagnostic imaging devices and radiotherapy (RT) units. The main objective of this research is to initiate a common platform for gathering SEE regional cancer data from the ground up to help these countries develop common cancer management strategies. Methods: To obtain detailed on-the- ground information, we developed separate questionnaires for two SEE groups: a) ONCO - oncologists regarding cancer treatment modalities and the availability of diagnostic imaging and radiotherapy equipment ; and b) REG - national radiation protection and safety regulatory bodies regarding diagnostic imaging and radiotherapy equipment in SEE facilities. Results: Based on responses from 13/17 ONCO participants (at least one from each country) and from 9/10 REG participants (all countries but Albania), cancer incidence rates are higher in those SEE countries that have greater access to diagnostic imaging equipment while cancer mortality-to-incidence (MIR) ratios are higher in countries that lack radiotherapy equipment. Conclusion: By combining unique SEE region information with data available from major global databases, we demonstrated that the availability of diagnostic imaging and radiotherapy equipment in the SEE countries is related to their economic development. While immediate diagnostic imaging and radiation therapy capacity building is necessary, it is also essential to develop both national and SEE- regional cancer registries in order to understand the heterogeneity of each country’s needs and to establish regional collaborative strategies for combating cancer

Wall shear stress describes the mechanical influence of blood flow on the arterial wall. In this review, we discuss the role of the wall shear stress in the development of atherosclerosis and its complications.Areas with chronically low, oscillating wall shear stress are most prone to plaque development and include outer bifurcation walls and inner walls of arches. In some diseases, patients have lower wall shear stress even in straight arterial segments; also, these findings were associated with atherosclerosis. High wall shear stress develops in the distal part (shoulder) of a stenosis and contributes to plaque destabilization. Wall shear stress changes are involved in the development of atherosclerosis. They are not fully understood yet and act in concert with tangential wall stress.

Aims Patients on chronic haemodialysis have a wide range of changes in cardiac function and structure, including left ventricular hypertrophy, dilation and diastolic dysfunction or pulmonary hypertension. All these changes were linked to increased mortality in previous studies. High-flow arteriovenous fistulas (AVF) are supposed to be a factor contributing to their development. This study investigated the early effect of surgical AVF blood flow (Qa) reduction on these changes in patients with or without heart failure changes. Methods and results Forty-two patients in chronic haemodialysis programme with high-flow AVF (Qa over 1500 mL/min), indicated for surgery for ≥1 of the following indications: 1.manifest heart failure; 2.hand ischemia; 3.advanced structural heart changes detected by echocardiography. The patients underwent echocardiography on selection visit, before blood flow reducing surgery and six weeks thereafter. The Qa reduction led to decrease of left ventricular mass (p = 0.02), end-diastolic volume (p = 0.008), end-diastolic diameter (p = 0.003) and left atrial volume (p = 0.0006). Diastolic function improved. Similarly, right ventricular diameter and right atrial volume decreased (p = 0.000001 and 0.00009, respectively) together with the decrease of estimated pulmonary artery systolic pressure. 81% of patients suffered from pulmonary hypertension prior to surgery, only 36% thereafter. Conclusion The surgical restriction of the hyperkinetic circulation leads to several improvements of heart structure and function, which was linked to higher mortality in other studies. The beneficial effect of Qa reduction is present even in patients without symptoms of heart failure. The contribution of AVF must be considered with structural or functional heart changes.

The management regarding metastatic colorectal cancer throughout Europe is not well known.To draw a European comparison of the management and prognosis of metastatic colorectal cancers.Factors associated with chemotherapy administration were identified through logistic regressions. Net survival was estimated and crude probabilities of death related to cancer and other causes using a flexible cumulative hazard model.Among the 13 227 patients with colorectal cancer diagnosed between 2010 and 2013 in cancer registries from 10 European countries, 3140 were metastatic. 62% of metastatic patients received chemotherapy. Compared to Spain, the related adjusted odds ratios ranged from 0.7 to 4.0 (P0.001) according to country. The 3-year net survival by country ranged between 16% and 37%. The survival gap between countries diminished from 21% to 10% when adjusting for chemotherapy, age and sex. Geographical differences in the crude probability of death related to cancer were large for patients70 or ≥80 years at diagnosis.Heterogeneity in the application of European guidelines partly explain these differences. General health between populations, accessibility to a reference centre, or provision of health care could also be involved. Further population-based studies are warranted to disentangle between these possible explanations.

This study was funded by the Compagnia di San Paolo, the Cariplo Foundation and the European Commission (grant number 801520 HP-JA-2017, Innovative Partnership for Action Against Cancer, iPAAC Joint Action). The sources of the funding played no role in designing the study, collecting, analyzing, or interpreting the data, writing the report, or deciding whether or not to submit the article for publication. This research was (partially) funded by Italian Ministry of Health "Ricerca Corrente" funds. Tyrosine kinase inhibitors (TKIs) have been improving the prognosis of patients with chronic myeloid leukemia (CML), but there are still large differences in survival among European countries. This raises questions on the added value of results from population-based studies, which use real-world data, compared to results of randomized controlled trials (RCTs) involving patients with CML. There are also questions about the extent of the findings on RCTs effectiveness for patients in the general population. We compare survival data extracted from our previous systematic review and meta-analysis of CML RCTs with the latest updated population-based survival data of EUROCARE-6, the widest collaborative study on cancer survival in Europe. The EUROCARE-6 CML survival estimated in patients (15-64 years) diagnosed in 2000-2006 vs. 2007-2013 revealed that the prognostic improvement highlighted by RCTs was confirmed in real-world settings, too. The study shows, evaluating for the first time all European regions, that the optimal outcome figures obtained in controlled settings for CML are also achievable (and indeed achieved) in real-world settings with prompt introduction of TKIs in daily clinical practice. However, some differences still persist, particularly in Eastern European countries, where overall survival values are lower than elsewhere, probably due to a delayed introduction of TKIs. Our results suggest an insufficient adoption of adequate protocols in daily clinical practice in those countries where CML survival values remain lower in real life than the values obtained in RCTs. New high-resolution population-based studies may help to identify failures in the clinical pathways followed there.

Arteriovenous fistula (AVF) is currently the hemodialysis access with the longest life expectations for the patients. However, even the AVF is at risk for many complications, especially the development of stenosis. The latter can not only lead to inadequate hemodialysis but also lead to AVF thrombosis. Duplex Doppler ultrasonography is a very precise method, in the hands of experienced professionals, for the diagnosis of AVF complications. In this review, we summarize the ultrasound diagnostic criteria of significant stenoses and their indication for procedural therapy.

Background: Heart failure (HF) is a frequent cause of morbidity and mortality of end-stage kidney disease (ESKD) patients on hemodialysis. It is not easy to distinguish HF from water overload. The traditional HF definition has low sensitivity and specificity in this population. Moreover, many patients on hemodialysis have exercise limitations unrelated to HF. Therefore, we postulated two new HF definitions ((1) Modified definition of the Acute Dialysis Quality Improvement working group; (2) Hemodynamic definition based on the calculation of the effective cardiac output). We hypothesize that the newer definitions will better identify patients with higher number of endpoints and with more advanced structural heart disease. Methods: Cohort, observational, longitudinal study with recording predefined endpoints. Patients ( n = 300) treated by hemodialysis in six collaborating centers will be examined centrally in a tertiary cardiovascular center every 6–12 months lifelong or till kidney transplantation by detailed expert echocardiography with the calculation of cardiac output, arteriovenous dialysis fistula flow volume calculation, bio-impedance, and basic laboratory analysis including NTproBNP. Effective cardiac output will be measured as the difference between measured total cardiac output and arteriovenous fistula flow volume and systemic vascular resistance will be also assessed non-invasively. In case of water overload during examination, dry weight adjustment will be recommended, and the patient invited for another examination within 6 weeks. A composite major endpoint will consist of (1) Cardiovascular death; (2) HF worsening/new diagnosis of; (3) Non-fatal myocardial infarction or stroke. The two newer HF definitions will be compared with the traditional one in terms of time to major endpoint analysis. Discussion: This trial will differ from others by: (1) detailed repeated hemodynamic assessment including arteriovenous access flow and (2) by careful assessment of adequate hydration to avoid confusion between HF and water overload.

Background Thyroid cancer is the most common malignancy of the endocrine system and it has become the fastest growing cancer among women. The suspected risk factors include increased exposure to ionizing radiation during childhood, environmental pollutants, possible iodine deficiency, and excessive iodine exposure. Aims To analyze the thyroid cancer incidence between 1980 and 2013 in Bulgaria and to determine the incidence rate before and after the introduction of universal salt iodization in 1994 in regions with different iodine deficiency levels. Study design Retrospective cohort. Methods The study was a retrospective analysis of the total number of thyroid cancer cases with all histological types in Bulgaria (thyroid cancer, ICD10 code C73), diagnosed between 01/01/1980 and 31/12/2013, and retrieved from the anonymous cancer registry database of the Bulgarian National Cancer Registry. Age-standardized rates of thyroid cancer per 100,000 persons were calculated for each year of the periods mentioned below by sex and age, utilizing the WHO world reference populations with a special statistical module of the Bulgarian National Cancer Registry’s software CancerRegBG, 2011. Incidence rates were reported by age, sex, and period of diagnosis (1980-86, 1987-93, 1994-99, 2000-2006, 2007-2013). Trends among males and females were analyzed separately, as well as by age category: 0-19, 20-44, 45-64, and 65+. Annual percentage changes of age-standardized incidence rates were analyzed by Joinpoint regression to determine trends using the Joinpoint statistical software SEER* Stat Software, Version 4.1.1, 2014. Results The age-standardized rates of thyroid cancer in Bulgaria has been increasing since 1990, being higher among women compared to men (4.68 vs 2.81). The highest age-standardized rates of thyroid cancer was observed in women in the 2007-2013 period. The only significant joinpoint was recorded in 1990 for females and in 1991 for males. The highest incidence rates was in the Smolyan district, a region with historically existing iodine deficiency and relatively high post-Chernobyl radiation exposure. Conclusion Our results showed that, in different regions, the age-standardized thyroid cancer rates between endemic and non-endemic differ greatly depending on the radiation dose from the Chernobyl accident. The role of iodine intake in thyroid cancer remains uncertain, but iodine deficiency could be a contributing factor to the increased risk of thyroid cancer.

Background: Decreased cerebral perfusion and oxygenation are common in hemodialysis patients. Magnitude of the arteriovenous fistula involvement in this phenomenon is not known. The aim of this study was to investigate the effect that a short-term arteriovenous fistula flow interruption has on cerebral oxygenation and to review and suggest possible explanations. Methods: In 19 patients, basic laboratory and clinical data were obtained and arteriovenous fistula flow volume was measured by ultrasonography. Baseline regional cerebral oxygen saturation (rSO2) was measured by near-infrared spectroscopy. Manual pressure was then applied on the fistula, resulting in total blood flow interruption. After 1 min of manual compression, rSO2 and blood pressure values were noted again. The compression-related change in rSO2 was assessed, as well as its association with arteriovenous fistula flow volume, blood pressure, and other parameters. Results: Mean cerebral rSO2 increased after arteriovenous fistula compression (from 53.6% ± 11.4% to 55.6% ± 10.8%; p = 0.000001; 95% confidence interval = 1.39–2.56). The rSO2 increase was higher in patients with lower rSO2 at baseline (r = −0.46; p = 0.045). Conclusion: A significant rise in cerebral oxygenation was observed following the manual compression of arteriovenous fistula. Therefore, the arteriovenous fistula could have a role in impaired cerebral oxygenation in hemodialysis patients.

Background: Arteriovenous fistulas (AVF) represent a low resistant circuit. It is known that their opening leads to decreased systemic vascular resistance, increased cardiac output and other hemodynamic changes. Possible competition of AVF and perfusion of other organs has been observed before, however the specific impact of AVF has not been elucidated yet. Previous animal models studied long-term changes associated with a surgically created high flow AVF. The aim of this study was to create a simple AVF model for the analysis of acute hemodynamic changes.Methods: Domestic female pigs weighing 62.6 ± 5.2 kg were used. All the experiments were held under general anesthesia. The AVF was created using high-diameter ECMO cannulas inserted into femoral artery and vein. Continuous hemodynamic monitoring was performed throughout the protocol. Near-infrared spectroscopy sensors, flow probes and flow wires were inserted to study brain and heart perfusion.Results: AVF blood flow was 2.1 ± 0.5 L/min, which represented around 23% of cardiac output. We observed increase in cardiac output (from 7.02 ± 2.35 L/min to 9.19 ± 2.99 L/min, p = 0.0001) driven dominantly by increased heart rate, increased pulmonary artery pressure, and associated right ventricular work. Coronary artery flow velocity rose. On the contrary, carotid artery flow and brain and muscle tissue oxygenation measured by NIRS decreased significantly.Conclusions: Our new non-surgical AVF model is reproducible and demonstrated an acute decrease of brain and muscle perfusion.

Supplemental material, sj-pdf-1-jva-10.1177_11297298221099843 for CZecking heart failure in patients with advanced chronic kidney disease (Czech HF-CKD): Study protocol by Jan Malik, Anna Valerianova, Satu Sinikka Pesickova, Zdenka Hruskova, Vladimira Bednarova, Pavel Michalek, Vladimir Polakovic and Vladimir Tesar in The Journal of Vascular Access

Chronic kidney disease (CKD) leads to profound metabolic and hemodynamic changes, which damage other organs, such as heart and brain. The brain abnormalities and cognitive deficit progress with the severity of the CKD and are mostly expressed among hemodialysis patients. They have great socio-economic impact. In this review, we present the current knowledge of involved mechanisms.

Brain tissue oxygenation (rSO2) measured by near-infrared spectroscopy (NIRS) is lower in hemodialysis patients than in the healthy population and is associated with cognitive dysfunction. The involved mechanisms are not known. We conducted this study to identify the factors that influence the rSO2 values in end-stage renal disease (ESRD) patients and to describe rSO2 changes during hemodialysis. We included a cohort of ESRD patients hemodialyzed in our institution. We recorded rSO2 using INVOS 5100C oximetry system (Medtronic, Essex, U.K.) and analyzed changes in basic laboratory values and hemodynamic fluctuations. Baseline rSO2 was lower in patients with heart failure (45.2±8.3 % vs. 54.1±7.8 %, p=0.006) and was significantly linked to higher red cell distribution width (RDW) (r=-0.53, p˂0.001) and higher BNP level (r=-0.45, p=0.01). The rSO2 value decreased in first 15 min of hemodialysis, this decrease correlated with drop in white blood count during the same period (r=0.43, p=0.02 in 10 min, r=0.43, p=0.02 in 20 min). Lower rSO2 values in patients with heart failure and higher RDW suggest that hemodynamic instability combined with vascular changes probably leads to worse cerebral oxygenation in these patients. Decrease of rSO2 in 15th minute of hemodialysis accompanied with a significant drop in leukocyte count could be explained by complement activation.

Background/Aims: High rates of cognitive impairment (CI) are an alarming problem in patients undergoing chronic hemodialysis (HD). Its pathophysiology remains unclear and there are indications that brain ischemia might be one of the key causes. Cerebral tissue oxygenation, as measured by near-infrared spectroscopy, is known to be decreased in HD patients. However, it is unknown whether CI is associated or not associated with lower cerebral oxygenation in these patients. The primary aim of our study was to probe this possible association. Our secondary aim was to assess other factors possibly related to cerebral ischemia and CI. Methods: Thirty-nine patients treated by chronic HD were included in this cross-sectional study. All measurements were performed before the initiation of an HD session. The Montreal Cognitive Assessment (MoCA) was administered according to published recommendations. Regional saturation of oxygen (rSO2) of the left frontal lobe was measured using the INVOS 5100C device. Basic medical history and laboratory data were recorded, and handgrip strength was analyzed. We used the unpaired t test to compare the rSO2 and other variables between cognitively normal patients (MoCA score ≥26) and those who displayed CI (MoCA score Results: Cognitively impaired patients had lower brain rSO2 values compared to cognitively normal patients (48 ± 9 vs. 57 ± 10%, p = 0.01). Among other variables, higher red cell distribution width (15.8 ± 1.9 vs. 13.8 ± 1.6%, p = 0.01) and lower hand grip strength (49.2 ± 23.3 vs. 99.3 ± 31.4 lbs, p < 0.001) also displayed a significant association with CI. The relation between rSO2 and MoCA score was significant after adjustment for age and gender (p = 0.007). Conclusion: Decreased brain oxygenation is associated with weaker cognitive performance in patients undergoing chronic HD. Further understanding the causes of cerebral ischemia in HD patients could lead to the prevention of cognitive decline in this population.

Funding Acknowledgements Grant of the Grant Agency of Charles University and grant of the Czech Health Research council Introduction Over 50% of patients treated by chronic haemodialysis programme die of cardiovascular diseases. Changes of heart structure and function can be detected by echocardiography. The most frequent changes are left ventricle hypertrophy (LVH) and its diastolic dysfunction. One of the considered contributing mechanisms is the hyperkinetic circulation. Purpose The aim of this study was to analyse the effect of high flow arteriovenous fistula (AVF) on eft ventricular hypertrophy and diastolic function. Materials and methods We included 30 patients with a high-flow arteriovenous fistula into the study, indicated for AVF blood flow reduction because of heart failure or hand ischemia. All the patients underwent echocardiographic examination and ultrasonographic measurement of AVF blood flow before and 6 weeks after the surgery. Results The AVF banding led to significant reduction of Qa (from 2977 ± 1408 to 1295 ± 610 mL/min; p ˂ 10-6, accompanied by significant decrease of cardiac index (from 4.34 ± 1.09 to 3.56 ± 0.90 L/min.m2). These findings were accompanied by significant reduction of left ventricle mass index (from 125 ± 31 to 116 ± 32 g/m2; p = 0.04) and by improvement of diastolic dysfunction grade (from 1.66 ± 0.67 to 1.14 ± 0.95; p = 0.03). The maximum velocity of tricuspid regurgitation decreased (from 3.1 ± 0.4 to 2.7 ± 0.5), and so did the left atrium volume index (from 47 ± 14 to 42 ± 15 mL/m2; p = 0.01). Conclusions LVH and diastolic dysfunction are frequent in haemodialysis patients; hyperkinetic circulation caused by high-flow arteriovenous fistula is one of the significant contributing mechanisms. Surgical reduction of AVF blood flow improved diastolic function of the left ventricle and reduced the hypertrophy in our patient population. AVF flow volume should be always considered during cardiological examination of haemodialysis patients.

Purpose: With better access to early diagnosis and appropriate treatment, cervical cancer (CC) burden decreased in several European countries. In Eastern European (EE) countries, which accessed European Union in 2004, CC survival was worse than in the rest of Europe. The present study investigates CC survival differences across five European regions, considering stage at diagnosis (local, regional and metastatic), morphology (mainly squamous versus glandular tumours) and patients’ age. Methods: We analysed 101,714 CC women diagnosed in 2000–2007 and followed-up to December 2008. Age-standardised 5-year relative survival (RS) and the excess risks of cancer death in the 5years after diagnosis were computed. Results: EE women were older and less commonly diagnosed with glandular tumours. Proportions of local stage cancers were similar across Europe, while morphology- and stage-specific RS (especially for non-metastatic disease) were lower in Eastern Europe. Adjusting for age and morphology, excess risk of local stage CC death for EE patients remained higher than that for other European women. Conclusion: Stage, age and morphology alone do not explain worse survival in Eastern Europe: less effective care may play a role, probably partly due to fewer or inadequate resources being allocated to health care in this area, compared to the rest of Europe.

List of ACCIS contributors = Monika Hackl, Anna Zborovskaya, Nadya Dimitrova, Zdravka Valerianova, Ladislav Dušek, Margit Mägi, Alain Monnereau, Jacqueline Clavel, Michel Velten, Anne-Valérie Guizard, Véronique Bouvier, Xavier Troussard, Anne-Sophie Woronoff, Emilie Marrer, Brigitte Trétarre, Marc Colonna, Olivier Ganry, Pascale Grosclaude, Berndt Holleczek, Zsuzsanna Jakab, Laufey Tryggvadóttir, Lucia Mangone, Franco Merletti, Stefano Ferretti, Bianca Caruso, Maria Michiara, Rosario Tumino, Fabio Falcini, Roberto Zanetti, Giovanna Tagliabue, Otto Visser, Giske Ursin, Ryszard Mężyk, Kamila Kepska, José Laranja Pontes, Maja Primic Žakelj, Rafael Fernández-Delgado, Marisa L Vicente Raneda, Enrique Almar Marqués, José Ramón Quirós Garcia, Arantza Lopez de Munain, Rafael Marcos-Gragera, Maria-Jose Sanchez-Perez, Maria Ramos Monserrat, Eva Ardanaz, Jaume Galceran, Staffan Khan, Claudia E Kuehni Christine Bouchardy, Fabio Levi, Isabelle Konzelmann, Sabine Rohrmann Sally Vernon, David H Brewster, Ceri White, Anastasia Dolya Background A deceleration in the increase in cancer incidence in children and adolescents has been reported in several national and regional studies in Europe. Based on a large database representing 1∙3 billion person-years over the period 1991–2010, we provide a consolidated report on cancer incidence trends at ages 0–19 years. Methods We invited all population-based cancer registries operating in European countries to participate in this population-based registry study. We requested a listing of individual records of cancer cases, including sex, age, date of birth, date of cancer diagnosis, tumour sequence number, primary site, morphology, behaviour, and the most valid basis of diagnosis. We also requested population counts in each calendar year by sex and age for the registration area, from official national sources, and specific information about the covered area and registration practices. An eligible registry could become a contributor if it provided quality data for all complete calendar years in the period 1991–2010. Incidence rates and the average annual percentage change with 95% CIs were reported for all cancers and major diagnostic groups, by region and overall, separately for children (age 0–14 years) and adolescents (age 15–19 years). We examined and quantified the stability of the trends with joinpoint analyses. Findings For the years 1991–2010, 53 registries in 19 countries contributed a total of 180335 unique cases. We excluded 15162 (8·4%) of 180335 cases due to differing practices of registration, and considered the quality indicators for the 165173 cases included to be satisfactory. The average annual age-standardised incidence was 137∙5 (95% CI 136∙7–138∙3) per million person-years and incidence increased significantly by 0∙54% (0∙44–0∙65) per year in children (age 0–14 years) with no change in trend. In adolescents, the combined European incidence was 176∙2 (174∙4–178∙0) per million person-years based on all 35138 eligible cases and increased significantly by 0·96% (0∙73–1∙19) per year, although recent changes in rates among adolescents suggest a deceleration in this increasing trend. We observed temporal variations in trends by age group, geographical region, and diagnostic group. The combined age-standardised incidence of leukaemia based on 48458 cases in children was 46∙9 (46∙5–47∙3) per million person-years and increased significantly by 0∙66% (0∙48–0∙84) per year. The average overall incidence of leukaemia in adolescents was 23∙6 (22∙9–24∙3) per million person-years, based on 4702 cases, and the average annual change was 0∙93% (0∙49–1∙37). We also observed increasing incidence of lymphoma in adolescents (average annual change 1·04% [0·65–1·44], malignant CNS tumours in children (average annual change 0·49% [0·20–0·77]), and other tumours in both children (average annual change 0·56 [0·40–0·72]) and adolescents (average annual change 1∙17 [0∙82–1∙53]). Interpretation Improvements in the diagnosis and registration of cancers over time could partly explain the observed increase in incidence, although some changes in underlying putative risk factors cannot be excluded. Cancer incidence trends in this young population require continued monitoring at an international level. Funding Federal Ministry of Health of the Federal German Government, the European Union’s Seventh Framework Programme, and International Agency for Research on Cancer

Objective. Ovarian cancers comprise several histologically distinct tumour groups with widely different prognosis. We aimed to describe the worldwide distribution of ovarian cancer histology and to understand what role this may play in international variation in survival. Methods. The CONCORD programme is the largest population-based study of global trends in cancer survival. Data on 681,759 women diagnosed during 1995–2009 with cancer of the ovary, fallopian tube, peritoneum and retroperitonum in 51 countries were included.We categorised ovarian tumours into six histological groups, and explored the worldwide distribution of histology. Results. During 2005–2009, type II epithelial tumours were the most common. The proportion was much higher in Oceania (73.1%), North America (73.0%) and Europe (72.6%) than in Central and South America (65.7%) and Asia (56.1%). By contrast, type I epithelial tumours were more common in Asia (32.5%), compared with only 19.4% in North America. From 1995 to 2009, the proportion of type II epithelial tumours increased from 68.6% to 71.1%, while the proportion of type I epithelial tumours fell from 23.8% to 21.2%. The proportions of germ cell tumours, sex cord-stromal tumours, other specific non-epithelial tumours and tumours of non-specific morphology all remained stable over time. Conclusions. The distribution of ovarian cancer histology varieswidely worldwide. Type I epithelial, germcell and sex cord-stromal tumours are generally associated with higher survival than type II tumours, so the proportion of these tumours may influence survival estimates for all ovarian cancers combined. The distribution of histological groups should be considered when comparing survival between countries and regions.

Background Cancer registries (CRs) are fundamental for estimating cancer burden, evaluating screening and monitoring health service performance. Stage at diagnosis—an essential information item collected by CRs—has been made available, for the first time, by CRs participating in EUROCARE-5. We analysed the quality of this information and estimated stage-specific survival across Europe for CRs with good data quality. Data and methods Sixty-two CRs sent stage (as TNM, condensed TNM or extent of disease) for 15 cancers diagnosed in 2000–2007. We assessed the quality, partly by comparing stage according to the three systems. We also developed procedures to reconstruct stage (categories: local, regional, metastatic and unknown) using information from all three systems, thus minimising the amount of missing information. Results Moderate-to-excellent stage concordance was found for practically all 24 CRs, for which it was possible to compare at least two staging systems. However, since stage was often incorrectly assigned, and information on the presence/absence of metastases was often lacking, data on only 7/15 cancers from 34/62 CRs (15 countries) were of sufficient quality for further analysis. Cases diagnosed ≥70 years had more advanced (or lacking) stage– and worse stage-specific survival than those Conclusions Many European CRs collect and record reasonably accurate stage information. Others have difficulties. Both the completeness of primary data and the accuracy of stage coding need to be improved in order for CRs to fulfil their expanding roles in cancer control. We propose our stage reconstruction/checking procedures as a means of fully exploiting the stage information provided by EUROCARE CRs. More advanced (or lacking) stage at diagnosis plus poorer stage-specific survival in the elderly are worrying.

BackgroundCognitive deficit is a common problem in end-stage renal disease (ESRD) patients. Ultrafiltration and hemodialysis lead to profound hemodynamic changes. The aim of this pilot study was to describe brain and hand oxygenation values in ESRD patients and their changes during hemodialysis.MethodsTwenty-seven patients treated by chronic hemodialysis and 17 controls patients of the same age were included in the study. Regional saturation of oxygen (SrO2) was measured at the brain frontal lobe and at the hand with dialysis access using the INVOS 5100C. In 17 of ESRD patients, SrO2was also monitored throughout hemodialysis. Finger systolic blood pressure and basic hemodialysis and laboratory data were collected.ResultsDialysis patients had lower brain and also hand SrO2values at rest (51.5 ± 10.9 vs. 68 ± 7%, p2to 47 ± 8%, p2decrease was related to the ultrafiltration rate, the hand SrO2decrease to the finger pressure and to blood hemoglobin.ConclusionsChronic dialysis patients suffer from tissue ischemia and that even worsens after the beginning of hemodialysis. This observation may contribute to the understanding of cognitive deficit etiology.

The prevalence of the left ventricular hypertrophy (LVH) is very high in end-stage renal disease treated by hemodialysis. Diastolic dysfunction is a frequent consequence and leads to the development of heart failure with preserved ejection fraction. New American/European echocardiographic guidelines for the assessment of diastolic function simplified the evaluation and were published recently. The aim of this study was to reveal if the new guidelines stratify asymptomatic hemodialysis patients by the levels of brain-natriuretic peptide (BNP). A cohort of 46 patients hemodialyzed in one center with the lack of overt heart failure, systolic dysfunction, arrhythmia or significant valvular disease were examined by echocardiography before and after a single hemodialysis and blood samples for BNP analysis were drawn at both occasions. The LVH was present in 53% of patients, concentric remodeling in another 17%. Higher indexed left ventricular mass was related to higher BNP levels (r = 0.58, p = 0.0001). Before hemodialysis, diastolic dysfunction was present in 61%: grade 1 in 25%, grade 2 in 21% and grade 3 in 8%. The higher grade of diastolic dysfunction was associated with the incremental increase of BNP. The post-dialysis echocardiography did not allow the assessment of diastolic function in as many as 37% of patients. Our study has shown that the application of the current guidelines for the assessment of diastolic function based on simple four criteria differentiate hemodialysis symptomless patients with preserved systolic function according to BNP levels. BNP levels also rose together with the left ventricular mass. The ratio E/eʹ medial seemed to be a better predictor of increased BNP than E/eʹ lateral or E/eʹ averaged.

Background: Creation of vascular access leads to considerable local haemodynamic changes with decreased hand perfusion. Distal limb tissues then represent a model of hand ischaemia effect on muscles. The aim of our study was to investigate how the presence of vascular access influences the hand muscle strength in end-stage renal disease patients. Methods: We included 52 chronically haemodialysed patients with upper limb access without clinical signs of hand ischaemia. Muscle strength was evaluated by dynamometry. Finger pressure was measured on the second and fourth fingers and averaged for further analysis. Thenar tissue oxygenation (rSO2) was analysed using near-infrared spectroscopy. All examinations were performed in both the hands. Basic laboratory analysis was added. Data were processed with unpaired t-test and correlation analysis. Results: Hands with dialysis access had lower values of handgrip strength (54.2 ± 29.1 lbs vs 48.6 ± 23.4 lbs, p = 0.0006), systolic finger pressure (127.1 ± 32.0 mmHg vs 101.4 ± 31.6 mmHg, p < 10−8) and of thenar rSO2 (45.8% ± 12.9% vs 42.5% ± 13.3%, p = 0.002). Muscle strength (handgrip) was directly related to the thenar oxygenation ( r = 0.36; p = 0.014) and to the finger systolic pressure ( r = 0.38; p = 0.007) on the access extremity. On the extremity without dialysis access, handgrip strength was inversely related to patient’s age ( r = −0.41, p = 0.003), dialysis vintage ( r = −0.32, p = 0.02) and red cell distribution width ( r = −0.37, p = 0.01). Conclusion: The presence of dialysis access leads to the decrease of finger pressure, oxygenation, and also muscle strength even in the absence of clinically overt hand ischaemia. All these parameters are interrelated. This study underlines the consequences of inadequate muscle perfusion.

BACKGROUND: Significant advances in the management of patients with lymphoid and myeloid malignancies entered clinical practice in the early 2000's. The EUROCARE-5 study database provides an opportunity to assess the impact of these changes at the population level by country in Europe. We provide survival estimates for clinically relevant haematological malignancies (HM), using the International Classification of Diseases for Oncology 3, by country, gender and age in Europe. METHODS: We estimated age-standardised relative survival using the complete cohort approach for 625, 000 adult patients diagnosed in 2000-2007 and followed up to 2008. Survival information was provided by 89 participating cancer registries from 29 European countries. Mean survival in Europe was calculated as the population weighted average of country-specific estimates. RESULTS: On average in Europe, 5-year relative survival was highest for Hodgkin lymphoma (81% ; 40, 625 cases), poorest for acute myeloid leukaemia (17% ; 57, 026 cases), and intermediate for non- Hodgkin lymphoma (59% ; 329, 204 cases), chronic myeloid leukaemia (53% ; 17, 713 cases) and plasma cell neoplasms (39% ; 94, 024 cases). Survival was generally lower in Eastern Europe and highest in Central and Northern Europe. Wider between country differences (>10%) were observed for malignancies that benefited from therapeutic advances, such as chronic myeloid leukaemia, chronic lymphocytic leukaemia, follicular lymphoma, diffuse large B-cell lymphoma and multiple myeloma. Lower differences (

Background Primary malignant brain tumours are rare but represent a serious health burden due to their poor survival. This manuscript describes the survival of malignant brain tumours in adults diagnosed 2000–2007 in Europe. Methods For this study we analysed patients archived in 86 European population-based cancer registries, followed up to 31st December 2008. Only primary malignant neuroepithelial brain tumours (with pathological confirmation) and primary malignant unspecified brain tumours without pathological confirmation were included. We estimated 1-year and 5-year relative survival (RS) weighted by age group and country. We also estimated country-specific and age-specific survival, together with survival differences between time periods (for 1999–2001, 2002–2004 and 2005–2007). Results Glioblastoma represents 49% of all brain tumours, followed by other/unspecified astrocytoma (18%), oligodendroglioma/oligoastrocytoma (9%), ependymoma (1.5%) and embryonal tumours (1%). Five-year RS was 20% for all tumours combined, but ranged from 58% for ependymoma to only 6% for glioblastoma and sharply decreased with increasing age. Differences between countries were relatively small, but generally RS in Ireland/United Kingdom (UK) and Eastern Europe was below the average. An increase in 1-year RS (up to 10–12%) was noted over time, being largest in Central and Northern Europe in patients between 45 and 74 years of age. Conclusions Despite an increase in 1-year RS in most European regions, the survival of primary malignant brain tumours is still poor. Disparities between countries were evident, being even larger at the end of the study period than at the beginning, suggesting differences in availability of the latest treatment modalities.

Background Previous population-based studies revealed major variation in survival for patients with colorectal cancer (CRC) in Europe by age and between different countries and regions, but also a sustained improvement in survival for patients with CRC in recent years. This EUROCARE-5 paper aims to update available knowledge from previous studies and to provide the latest survival estimates for CRC patients from Europe. Methods The study analysed data of patients diagnosed with CRC from population-based cancer registries diagnosed in 29 European countries. Estimates of 1-year and 5-year relative survival (RS) were derived for patients diagnosed in 2000–2007 by European region, country and age at diagnosis. Additionally to these cohort estimates, time trends in 5-year RS were obtained for the calendar periods 1999–2001 and 2005–2007, using the period analysis methodology. Results European average 5-year RS for patients diagnosed with colon and rectum cancer was 57% and 56%, respectively. The analyses showed persistent differences in cancer survival across Europe with lowest survival for CRC patients observed in Eastern Europe. The analyses further showed a strong gradient in age-specific survival. Even though the study revealed sustained improvement in patient survival between 1999–2001 and 2005–2007 (absolute increase of 4 and 6 percentage points for colon and rectum, respectively), the differences in the survival for CRC patients observed at the beginning of the millennium persisted over time. Conclusion Although survival for CRC patients in Europe improved markedly in the study period, significant geographic variations and a strong age gradient still persisted. Enhanced access to effective diagnostic procedures and treatment options might be the keys to reducing the existing disparities in the survival of CRC patients across Europe.

OBJECTIVE: Ovarian cancers comprise several histologically distinct tumour groups with widely different prognosis. We aimed to describe the worldwide distribution of ovarian cancer histology and to understand what role this may play in international variation in survival. METHODS: The CONCORD programme is the largest population-based study of global trends in cancer survival. Data on 681,759 women diagnosed during 1995-2009 with cancer of the ovary, fallopian tube, peritoneum and retroperitonum in 51 countries were included. We categorised ovarian tumours into six histological groups, and explored the worldwide distribution of histology. RESULTS: During 2005-2009, type II epithelial tumours were the most common. The proportion was much higher in Oceania (73.1%), North America (73.0%) and Europe (72.6%) than in Central and South America (65.7%) and Asia (56.1%). By contrast, type I epithelial tumours were more common in Asia (32.5%), compared with only 19.4% in North America. From 1995 to 2009, the proportion of type II epithelial tumours increased from 68.6% to 71.1%, while the proportion of type I epithelial tumours fell from 23.8% to 21.2%. The proportions of germ cell tumours, sex cord-stromal tumours, other specific non-epithelial tumours and tumours of non-specific morphology all remained stable over time. CONCLUSIONS: The distribution of ovarian cancer histology varies widely worldwide. Type I epithelial, germ cell and sex cord-stromal tumours are generally associated with higher survival than type II tumours, so the proportion of these tumours may influence survival estimates for all ovarian cancers combined. The distribution of histological groups should be considered when comparing survival between countries and regions.

Objective. Ovarian cancer comprises several histological groups with widely differing levels of survival. We aimed to explore international variation in survival for each group to help interpret international differences in survival from all ovarian cancers combined. We also examined differences in stage-specific survival. Methods. The CONCORD programme is the largest population-based study of global trends in cancer survival, including data from 60 countries for 695,932 women (aged 15–99 years) diagnosed with ovarian cancer during 1995–2009. We defined six histological groups: type I epithelial, type II epithelial, germ cell, sex cord-stromal, other specific non-epithelial and non-specific morphology, and estimated age-standardised 5-year net survival for each country by histological group. We also analysed data from67 cancer registries for 233,659 women diagnosed from 2001 to 2009, for whom information on stage at diagnosis was available. We estimated agestandardised 5-year net survival by stage at diagnosis (localised or advanced). Results. Survival fromtype I epithelial ovarian tumours for women diagnosed during 2005–09 ranged from40 to 70%. Survival from type II epithelial tumours was much lower (20–45%). Survival fromgermcell tumours was higher than that of type II epithelial tumours, but also varied widely between countries. Survival for sex-cord stromal tumours was higher than for the five other groups. Survival from localised tumours was much higher than for advanced disease (80% vs. 30%). Conclusions. There is wide variation in survival between histological groups, and stage at diagnosis remains an important factor in ovarian cancer survival. International comparisons of ovarian cancer survival should incorporate histology.

PurposeDysfunction and loss of patency of dialysis arteriovenous grafts (AVGs) are serious causes of morbidity in patients on dialysis. Various risk factors associated with shorter AVG patency have been blamed, but the results of the studies were controversial. The aim of this study was to assess if associated diseases, biochemical markers and other parameters associated with atherosclerosis influence patency of AVGs in a large vascular access centre.MethodsWe conducted a retrospective study that included patients with AVGs patent for at least 3 weeks after creation. We included variables associated with atherosclerosis into the analysis (coronary artery disease, diabetes mellitus, chronic heart failure, arterial hypertension, smoking history and cholesterol and triglyceride levels) and characteristics of the graft (shape, feeding artery). The data was assessed using log-rank (Cox-Mantel) test. The differences were shown using Kaplan-Meier graphs. The observation period was limited to 1000 days after access creation.ResultsOverall, 338 patients were included in the study. Significantly higher risk of access failure was associated with presence of coronary artery disease (p = 0.0035). Higher serum cholesterol levels were associated with longer survival of the graft in 1000 days of surveillance (p = 0.04).ConclusionsCoronary artery disease negatively influences the cumulative patency of vascular access. Higher serum cholesterol levels are associated with lower AVG failure risk over a 1000-day period, which probably corresponds to the worse disease status of the patients with lower cholesterol values.

In most developed countries, incidence of cervical cancer declined likely due to well-established cervical cancer screening programs. However, such decline has not been identified in Eastern Europe, where such programs are not well established.This study utilized data of the Bulgarian Cancer Registry for the period 1993-2013. Age-standardized incidence and mortality trends were analyzed using Joinpoint regression. Maps were created to illustrate spatial distributions of rates.The northern region of Bulgaria showed a larger cervical cancer burden than the southern region and rural women tended to be diagnosed at older ages (p0.0001) and later stages (p0.0001) than urban women. The distribution of disease stages changed over the 21 years, with most common stages of diagnosis being stage II in 1993 (39.2%) to stage I in 2013 (44.7%; p0.0001). While age-standardized mortality slightly increased over the 21 years (from 4.8 to 5.2 per 100,000; p=0.009), age-standardized incidence increased from 14.0 to 21.4 per 100,000 up until 2006 (p0.001), after which it plateaued.The lack of a similar plateau in mortality may be because the second most prevalent stage of diagnosis in recent years was stage III, indicating diagnosis at advanced symptomatic stages. Cervical cancer incidence is expected to continue to decrease if screening programs are strengthened and human papillomavirus vaccines are widely utilized. As Bulgaria has shared cervical cancer trends with other Eastern European countries in the past, it may be beneficial to develop future prevention interventions based on a regional, rather than a country-specific level.

Background: Repeated inter-dialysis water retention contributes to the development of left ventricular hypertrophy and failure, which is responsible for significant mortality of end-stage renal disease (ESRD) patients. The left atrium has a thin wall, which makes it even more prone to preload changes. In the general population with heart failure with preserved ejection fraction (HFpEF), left atrial function is even worse than that in patients with reduced ejection fraction. We hypothesized that repeated water retention is related to left atrial dysfunction in ESRD patients treated by hemodialysis and that the expected changes would be related to the brain natriuretic peptide (BNP) levels. Methods: Forty six patients were enrolled. Left atrial end-diastolic and end-systolic volumes and left atrial ejection fraction (LAEF) were recorded by echocardiography just before and just after dialysis and then analyzed offline. Moreover, BNP was analyzed also prior to dialysis and after. Effects of dialysis were tested using paired t test and the correlation analysis was applied to test associations. Results: LAEF was inversely related to the dialysis vintage (r = -0.62, p = 0.001) and patient's age (r = -0.48, p = 0.005) and it did not increase after dialysis despite the decrease of left atrial volume. BNP was related to left atrial volume index (r = 0.45, p = 0.019) and to LAEF (r = -0.57, p = 0.003). Conclusions: LAEF is decreased especially in long-term dialyzed patients and does not improve after dialysis despite the decrease of left atrial volume. Inadequate contractility reserve of the left atrium is similar to the non-ESRD patients with HFpEF and might help explain the high prevalence of heart failure in ESRD patients.

The burden of cervical cancer varies considerably in the European Union (EU). In this article, we describe trends in incidence of and mortality from this cancer in the two most affected areas: the Baltic countries (Estonia, Latvia and Lithuania) and Southeast Europe (Bulgaria and Romania). Incidence data were obtained from the national cancer registries. Data on population and number of deaths from uterine cancers were extracted from the World Health Organization mortality database. Mortality rates were corrected for inaccuracies in the death certification of not otherwise specified uterine cancer. Joinpoint regression was used to study the annual variation of corrected and standardized incidence and mortality rates. Changes were assessed by calendar period and age group, whereas the evolution by birth cohort was synthesized by computing standardized cohort incidence/mortality ratios. Joinpoint regression revealed rising trends of incidence (in Lithuania, Bulgaria and Romania) and of mortality (in Latvia, Lithuania, Bulgaria and Romania). In Estonia, rates were rather stable. Women born between 1940 and 1960 were at continuously increasing risk of both incidence of and mortality from cervical cancer. Although some quality issues in the registration of cancer and causes of death cannot be ignored, the trends indicate increased exposure to human papillomavirus infection and absence of effective screening programs. Rising trends of cervical cancer in the most affected EU member states reveal a worrying pattern that warrants urgent preventive actions.

The aim of the study was to compare current policy, Organisation and coverage of cervical cancer screening programmes in the European Union (EU) member states with European and other international recommendations. According to the questionnaire-based survey, there are large variations in cervical cancer screening policies and inadequacies in the key organisational elements of the programme such as registration and monitoring required for quality-assurance and fail-safe mechanisms. Based on data from available screening registers, coverage of the screening test taken within the population-based programme was below 80% in all programmes, ranging from 10% to 79%. The screening capacity is satisfactory in most EU member states, however, and there is even over-capacity in several countries. There are also countries which do not have an acceptable capacity yet. Control of proper capacity along with education, training and communication among women, medical professionals and authorities are required, accordingly The study indicates that, despite substantial efforts, the recommendations of the Council of the EU on organised population-based screening for cervical cancer are not yet fulfilled. Decision-makers and health service providers should consider stronger measures or incentives in order to improve cervical cancer control in Europe. (C) 2009 Elsevier Ltd. All rights reserved.

We report our time-resolved transient photoresponse studies of current-biased Hg-Ba-Ca-Cu-O superconducting microbridges excited by 100-fs-wide and 800-nm-wavelength laser pulses. Our devices consisted of 20-mum wide and 30-mum long bridges, incorporated into a 0.1-mm-wide signal line of the coplanar strip transmission line. The structures were patterned in 400-nm-thick precursor films grown on substrates by room-temperature magnetron sputtering and, subsequently, exposed to an ex-situ high-temperature mercuration process. The resulting structures consisted of a c-axis-oriented, predominantly Hg-1212 compound with the onset superconducting critical temperature Tc,on around 110 K. At low temperatures (far below Tc ), under low bias current and low optical excitation, the microbridge photoresponse signal was a positive, ~90-ps-wide (measurement- limited) pulse followed by a negative component and was related to the kinetic-inductive response. At high temperatures, or when the bias current was near the bridge critical current, we observed an additional slow resistive response due to the bolometric effect. The observed ultrafast photoresponse dynamics in our Hg-Ba-Ca-Cu-O bridges make this material very promising for optical photodetector and mixer applications.

Background Quality assurance of cancer care is of utmost importance to detect and avoid under and over treatment. Most cancer data are collected by different procedures in different countries, and are poorly comparable at an international level. EURECCA, acronym for European Registration of Cancer Care, is a platform aiming to harmonize cancer data collection and improve cancer care by feedback. After the prior launch of the projects on colorectal, breast and upper GI cancer, EURECCA's newest project is collecting data on pancreatic cancer in several European countries. Methods National cancer registries, as well as specific pancreatic cancer audits/registries, were invited to participate in EURECCA Pancreas. Participating countries were requested to share an overview of their collected data items. Of the received datasets, a shared items list was made which creates insight in similarities between different national registries and will enable data comparison on a larger scale. Additionally, first data was requested from the participating countries. Results Over 24 countries have been approached and 11 confirmed participation: Austria, Belgium, Bulgaria, Denmark, Germany, The Netherlands, Slovenia, Spain, Sweden, Ukraine and United Kingdom. The number of collected data items varied between 16 and 285. This led to a shared items list of 25 variables divided into five categories: patient characteristics, preoperative diagnostics, treatment, staging and survival. Eight countries shared their first data. Conclusions A list of 25 shared items on pancreatic cancer coming from eleven participating registries was created, providing a basis for future prospective data collection in pancreatic cancer treatment internationally.

In Bulgaria, there are over 3700 cases diagnosed with breast cancer annually and over 3300 with gynecological cancers. The purpose of this study was to estimate the burden of breast and gynecological cancers in Bulgaria, analyzing trends of incidence, mortality and survival for the past two decades.Data from the Bulgarian National Cancer Registry for women diagnosed with cancer of breast (C50, ICD10), cervix uteri (C53), corpus uteri (C54) and ovary (C56) during 1993 - 2009 were analyzed. Age-standardized incidence and mortality rates (ASR) per 100,000 persons were calculated using the world standard population. Average annual percent changes (AAPC) for 1993-2009 were estimated by Joinpoint regression. The observed survival was analyzed with the Life Table method for two periods: 1993-1997 and 2005-2009.Incidence rates of the most frequent cancers among Bulgarian women are increasing - from 1.7% to 2.6% annually. Mortality rates are decreasing significantly for breast (-0.8% annually) and increasing for corpus uteri cancers (4.9% annually). Survival for all sites increased from 3 to 8% over the study period. We observed greater proportion of cases diagnosed in stage I in 2009 than in 1993, for the 4 sites.These results indicate some differences in trends in incidence and mortality of the reviewed sites compared with other European countries, highlighting the need for more strict adherence to integrated treatment standards and the necessity of introduction of population screening programs.

The accident which occurred during the night of April 25-26, 1986 in reactor 4 of the Chernobyl nuclear power plant in the Ukraine released considerable amounts of radioactive substances into the environment. Outside the former USSR, the highest levels of contamination were recorded in Bulgaria, Austria, Greece and Romania, followed by other countries of Central, Southeast and Northern Europe. Studies of the health consequences of the accident have been carried out in these countries, as well as in other countries in Europe. This report presents the results of a critical review of cancer studies of the exposed population in Europe, carried out on the occasion of the 10th anniversary of the Chernobyl accident. Overall, three is no evidence to date of a major public health impact of the Chernobyl accident in the field of cancer in countries of Europe outside the former USSR.

BACKGROUND Bulgaria has undergone considerable social changes in the last 40 years, including a transition from a 75% rural to a 75% urban population. These changes might be expected to be reflected in disease rates. The Bulgarian cancer registry has computerized data on cancer incidence throughout the country from 1981 onwards. METHODS Incidence rates in Bulgaria from 1981 to 1990 of cancers of the lung, stomach, large bowel, prostate and bladder in males and of cancers of the breast, lung, stomach, large bowel, cervix and corpus uteri in females were analysed with particular attention to time trends, age-specific changes in rates and urban/rural differences. Poisson regression was used for statistical analysis. RESULTS Male rates of cancers of the lung, large bowel, prostate and bladder increased significantly over the period, with average annual increases of 0.4%, 2.9%, 1.3% and 2.3% respectively. In females, rates of cancers of the breast, cervix and corpus uteri increased significantly, with average annual increases of 1.3%, 1.9%, and 2.9%. In both sexes, stomach cancer incidence declined significantly, by 3.0% per year for males and 3.6% per year for females. Rural rates were lower than urban rates for most cancers, particularly in the higher age groups. The decline in male stomach cancer rates was confined to rural areas. The increases in rates of lung cancer and prostate cancer in males and of colorectal cancer and breast cancer in females were most rapid in urban areas. CONCLUSIONS Substantial changes in rates of various cancers have taken place from 1981 to 1990, in particular increases in rates of breast cancer and large bowel cancer in women resident in urban areas. It is suggested that dietary changes may be responsible for some of these changes.

Background In Bulgaria the previously (1970–1985) existing population based cervical cancer screening was replaced in the early 1990s with an opportunistic model due to political and socioeconomic reasons. As a result, in the last 20 years, cervical cancer incidence and mortality rates steady increased. The objective of the EUROCHIP project in Bulgaria was to evaluate the readiness of the health system as well as health providers' attitudes to implementation in the country of a population based screening program for cervical cancer. Methods Using a structured questionnaire, a convenience sample of medical specialists representing different actors involved in cervical cancer prevention, treatment, financing and policy were interviewed. Results The majority of interviewed practitioners worried that organization and implementation of an effective population-based cervical cancer screening program is not possible in the current unstable health system. A nostalgic attitude to the cervical cancer screening, performed in the past and pessimistic view on the capability of the current health system to cope are strong. As main barriers to implementation of an effective program were pointed financial and organizational ones. Motivation for gynecologists to perform smear test should include better information, organization and payment. Discussion Medical specialists in Bulgaria are aware of the alarming rates of cervical cancer incidence and mortality in the country. However, due to the insufficient communication and interaction between policy makers and front-line health care staff, they do not have enough information on the ongoing programs. Absence of health policy regarding screening is considered as main barrier for implementation of an effective screening program.

Cyclophosphamide (CY)-containing chemotherapy is usually characterized as moderately emetogenic. The aim of this study was to evaluate the efficacy of different antiemetics in the control of acute emesis in repeated cycles of moderately emetogenic chemotherapy.A total of 101 patients with breast cancer (41, 40.6%), Hodgkin's disease (46, 45.5%) and non-Hodgkin's lymphoma (14, 13.9%) were studied. These patients received standard protocols of CY-based (/=750 mg/m(2)) moderately emetogenic chemotherapy. Intravenous (i.v.) bolus metoclopramide (MCL), ondansetron (OND) and their combinations with corticosteroids (CS) were administered to the patients. The MCL-alone group of patients was used as control group. Emesis was evaluated during the first 3 courses of chemotherapy according to the internationally accepted criteria. All calculations were performed using the SPSS-5.0 statistical computing package.During the first course of chemotherapy no differences in the efficacy between the control group and the other groups were noted (p0.05). On the contrary, during the next 2 courses the efficacy of MCL progressively decreased and OND, OND plus CS and MCL plus CS showed significantly higher efficacy compared with MCL alone (p0.05). Excluding MCL alone, the other antiemetics showed similar efficacy in the 2nd and 3rd course of chemotherapy (p0.05). Patients aged over 35 years had more severe emesis.The combination of MCL plus CS showed similar efficacy compared with OND and OND plus CS, and is cost-effective. The control of acute emesis in the first course and the patients' age are significant factors, influencing the efficacy of the antiemetic therapy in repeated courses of moderately emetogenic chemotherapy.

To evaluate the response rate and overall survival (OS) of chemotherapy-naïve patients with metastatic colorectal adenocarcinoma treated with 4 different chemotherapy regimens.One hundred fifty-eight patients with metastatic colorectal cancer (CRC) were included in this prospective study. The treatment regimens were as follows: a) Intraarterial (i.a.) chemotherapy: 5-fluorouracil (5-FU) 600 mg/m(2)/day by 120 hour-infusion, mitomycin C 8 mg/m(2) day 1, and epirubicin 80 mg/m(2) day 5, every 3 weeks, b) Intravenous (i.v.) chronochemotherapy: 5-FU 800 mg/m(2) i.v. infusion during 18.00 h-06.00h, leucovorin (LV) 100 mg/m(2) i.v. infusion during 18.00h-06.00h; and cisplatin 20mg/m(2) i.v. infusion, during 10.00h-18.00 h, all given on days 1-5, every 3 weeks, c) Scheme: 5-FU 500 mg/m(2) i.v. bolus, days 1-5, vincristine 1.2 mg/m(2) i.v. bolus, day 1, CCNU 120 mg/m(2) per so (p.o.), day 5, every 3 weeks. Scheme I was used as control group, d) Scheme II: 5-FU 425 mg/m(2) i.v. bolus, days 1-5, and LV 50 mg/m(2) i.v. bolus, days 1-5, every 3 weeks. The patients received 3-26 cycles of chemotherapy. The results taken were compared using the Kaplan-Meier life-table method, logrank test, Cox proportional hazard model, and Cox model with time-dependent covariates.Nine (26%) out of 34 patients with i.a. chemotherapy achieved complete response (CR), 8 (24%) partial response (PR), and 11 (32%) stable disease (SD). In the group of 42 patients with chronochemotherapy 4 (10%) achieved CR, 15 (36%) PR and 12 (28%) SD. In the group of 61 patients with conventional treatment with 5-FU and LV (scheme II) no CR was achieved with 11 (18%) patients responding partially. In the control group of treatment (scheme I) with 21 patients PR was observed in 2 (10%) patients. Patients with i.a. chemotherapy and chronochemotherapy achieved a similar OS, which was better than OS of scheme II. The survival was worst with scheme I.I.a. chemotherapy and chronochemotherapy showed an almost equivalent efficacy in terms of response rates, which were clearly superior to those achieved by schemes I and II. Also, OS was significantly better in the patients treated with i.a. chemotherapy and chronochemotherapy compared to patients treated with scheme II. The worst survival was seen in scheme I patients.