[Clinical guidelines for diagnosis, treatment and monitoring of patients with non-invasive breast cancer]. / Klinicke smjernice za dijagnostiku, lijecenje i pracenje bolesnika s neinvazivnim rakom dojke.

Breast cancer is the most common malignancy in women. Early diagnosis and more effective treatment of invasive breast cancer resulted in significant mortality reduction, improvement of survival and the quality of life of the patients. The management od non-invasive breast cancer, on the contrary, is still controversial and the problem of overdiagnosis and overtreatment of patients come to evidence. In the following text a multidisciplinary team of experts brings the first consensus guidelines aimed to standardize and optimize the criteria and management in diagnosis, treatment and monitoring of non-invasive breast cancer patients in the Republic of Croatia.

Urban-rural differences in a population-based breast cancer screening program in Croatia.

AIM: To investigate urban-rural differences in the distribution of risk factors for breast cancer. METHODS: We analyzed the data from the first round of the "Mamma" population based-screening program conducted in Croatia between 2007 and 2009 and self-reported questionnaire results for 924 patients with histologically verified breast cancer. Reproductive and anthropometric characteristics, family history of breast cancer, history of breast disease, and prior breast screening history were compared between participants from the city of Zagreb (n = 270) and participants from 13 counties with more than 50% of rural inhabitants (n = 654). RESULTS: The screen-detected breast cancer rate was 4.5 per 1000 mammographies in rural counties and 4.6 in the city of Zagreb, while the participation rate was 61% in rural counties and 59% in Zagreb. Women from Zagreb had significantly more characteristics associated with an increased risk of breast cancer (P<0.001 in all cases): no pregnancies (15% vs 7%), late age of first pregnancy (≥ 30 years) (10% vs 4%), and the most recent mammogram conducted 2-3 years ago (32% vs 14%). Women from rural counties were more often obese (41% vs 28%) and had early age of first live birth (<20 years) (20% vs 7%, P<0.001 for both). CONCLUSION: Identification of rural-urban differences in mammography use and their causes at the population level can be useful in designing and implementing interventions targeted at the reduction of inequalities and modifiable risk factors.

Skin cancers in Croatia, 2003-2005: epidemiological study.

This study presents the incidence of major nonmelanoma skin cancers (major NMSCs), other nonmelanoma skin cancers (other NMSCs) and malignant melanoma (MM) in Croatia. The skin cancers recorded between 1 January 2003 and 31 December 2005 were retrospectively analyzed. Until 2003, the incidence of major NMSCs and other NMSCs was not estimated in Croatia. Incident cases of NMSCs were identified by the use of a questionnaire distributed to dermatology departments in Croatia and then collected at the University Department of Dermatology and Venereology, Zagreb University Hospital Center, and from the records kept at the National Cancer Registry. Incident cases of MM were extracted from the National Cancer Registry. During the 3-year period, 9,479 cases of major NMSCs are recorded, 4,622 (49%) in male and 4,857 (51%) in female patients. The crude incidence rate was 72.1/100,000 for males and 70.3/100,000 for females. Basal cell carcinoma (BCC) was the most common major NMSC in both sexes. In the total number of major NMSCs, there were 7,244 cases of BCC. Squamous cell carcinoma (SCC) was the second most common major NMSC. There were 1,860 SCC cases. The crude incidence rate was 54.9/100,000 for BCC in males, 53.9/100,000 in females, and 14.6/100,000 for SCC in male and 13.4/100,000 in female patients. Other NMSCs were registered in 119 cases (53% male and 47% female). The crude incidence rate was 0.9/100,000 for male and 0.8/100,000 for female patients. MM was registered in 1,427 cases (48% male and 52% female.) The crude incidence rate was 10.7/100,000 for males and females. These results will serve as reference for studying the patterns of descriptive epidemiology of major NMSCs, other NMSCs and MM in Croatia and Europe in the forthcoming years.

[Salt and cancer]. / Sol i rak.

Besides cardiovascular disease, a high salt intake causes other adverse health effects, i.e., gastric and some other cancers, obesity (risk factor for many cancer sites), Meniere's disease, worsening of renal disease, triggering an asthma attack, osteoporosis, exacerbation of fluid retention, renal calculi, etc. Diets containing high amounts of food preserved by salting and pickling are associated with an increased risk of cancers of the stomach, nose and throat. Because gastric cancer is still the most common cancer in some countries (especially in Japan), its prevention is one of the most important aspects of cancer control strategy. Observations among Japanese immigrants in the U.S.A. and Brazil based on the geographic differences, the trend in cancer incidence with time, and change in the incidence patterns indicate that gastric cancer is closely associated with dietary factors such as the intake of salt and salted food. The findings of many epidemiological studies suggest that high dietary salt intake is a significant risk factor for gastric cancer and this association was found to be strong in the presence of Helicobacter (H.) pylori infection with atrophic gastritis. A high-salt intake strips the lining of the stomach and may make infection with H. pylori more likely or may exacerbate the infection. Salting, pickling and smoking are traditionally popular ways of preparing food in Japan and some parts of Asia. In addition to salt intake, cigarette smoking and low consumption of fruit and vegetables increase the risk of stomach cancer. However, it is not known whether it is specifically the salt in these foods or a combination of salt and other chemicals that can cause cancer. One study identified a mutagen in nitrite-treated Japanese salted fish, and chemical structure of this mutagen suggests that it is derived from methionine and that salt and nitrite are precursors for its formation. Working under conditions of heat stress greatly increased the workers' salt excretion through perspiration. Workers exposed to heat stress consumed as much as 13-38 g salt daily. As salt strongly enhances and promotes chemical gastric carcinogenesis and H. pylori infection in both humans and animals, there is an association between work, salt intake, and development of stomach cancer. Reducing salt intake, especially during pregnancy, also reduces the risk of developing breast cancer and many other diseases, as well as obesity. The risk of most cancers is reduced by losing weight. The geographical data and analyses currently available suggest that road salt (road salting in winter) may be associated with elevated mortality from cancer of the breast, lung, esophagus, throat, larynx, large intestine, rectum and bladder. There is no available literature on the health impacts of road salt. The cause and effect relationships cannot be established without further studies.

[National program of early detection of cancer in Croatia]. / Rano otkrivanje raka u hrvatskoj.

INTRODUCTION: A well organized and conducted program of cancer screening at the population level should be scientifically based, cost-effective at long term, and designed on the good practice examples. Appropriate diagnosis and treatment should be warranted by high rate of target population inclusion, while appropriate diagnosis and treatment should be warranted for those with positive findings. AIM: The aim is to present implementation of the national programs of early detection of breast and colon cancer in Croatia. RESULTS: In the first cycle screening for breast cancer (since the end of 2006), a total of 720,981 women were invited for mammography, of which 58.5% presented for screening, with more than 1500 cases of breast cancer detected. A total of 808,913 tests were distributed for colon cancer screening from the end of 2007 to the beginning of 2010, of which only 19.9% were returned, 7.7% of these positive. Colonoscopy yielded 77.5% of pathologic findings, including 388 (5.99%) carcinomas, 2492 (38.46%) polyps, 1641 hemorrhoids and 998 diverticula. CONCLUSION: In Croatia, the public health service has made maximal use of all its resources in the national programs of early cancer detection. Great efforts and time, along with continuous education of all those involved in the program, have been invested in preparatory activities, organization and coordination of the program, contacts and collaboration with family physicians, specialist units, mass media, regional and local authorities, partnership with non-governmental societies, monitoring, evaluation and quality control.

Croatian Adult Health Survey--a tool for periodic cardiovascular risk factors surveillance.

National risk factors surveys present very important tool for gathering population based health related information for policy. Croatian Adult Health Survey (CAHS) is such a tool, intended to collect population-based, representative and authoritative information on cardiovascular risk factors prevalence. The CAHS sample was designed to provide nearly complete coverage (98%) of the Croatian adult population, based on the random selection of the adult member of the household that was selected in the complex sampling scheme. Additionally, seven-step weighting scheme was applied to the dataset, in order to further increase the representativeness of the sample which is consequently considered to be representative for six geographical and administrative regions of Croatia, while it is considered only to be informative for the county-based estimates. The first cycle of the project took place in 2003, with a total of 9,070 respondents. The second project cycle is taking place in 2008. It has now been converted into the follow-up study (re-surveying the 2003 sample) and is being further supplemented with additional questions, qualitative investigation module and an intervention performed by the public health nurses. The CAHS provides not only the basis for health information for policy, but also serves as a platform for a number of ongoing public health collaborations and a valuable public health research resource.

Regional pattern of cardiovascular risk burden in Croatia.

The objective of this study was to investigate regional gradient of a synthetic cardiovascular burden (CVRB) in Croatia. Analysis was based on a multistage stratified sample representative of general adult population in six regions of Croatia (Croatian Adult Health Survey). Synthetic CVRB was defined by incidents (heart attack, stroke), blood pressure, overweight/obesity (BMI, waist circumference), and risky behaviours (smoking, physical inactivity, high alcohol consumption, inadequate nutrition). Total CVRB in Croatia was 44.7% for men and 50.3% for women. Combining both high and moderate CVRB, men were found to be under more risk than women (72.8% vs. 61.7%, respectively). The result showed an east-north-west gradient in continental Croatia, with high CVRB in Eastern (40.2%) and Central region (44.3%), City of Zagreb (45.7%) and Northern region (53.1%). Mountainous region had the lowest prevalence of respondents with high CVRB (39.2%). Coastal region with the prevalence of 46.3% of high CVRB was nearly the same as the City of Zagreb. The results suggest the presence of substantial regional differences in the cardiovascular risk burden.

Trends and regional disparities in ischemic heart disease and cerebrovascular disease in Croatia, 1997-2006.

The aim of this study was to analyze mortality and hospital morbidity from ischemic heart disease (IHD) and cerebrovascular disease (CVD) in the population aged 18+ years in different regions of Croatia, in 1997 to 2006 period. Mortality data were supplied by Central Bureau of Statistics, while hospital morbidity data were obtained from hospital discharge database at Croatian National Institute of Public Health. In Mediterranean region rates of IHD mortality were lower, while rates of hospitalization due to IHD have been higher than those for Croatia in the entire period. Rates of IHD mortality for Continental part have not been different from mean rates for Croatia while rates of hospitalization due to IHD have been lower than rates for Croatia in entire period. Rates of CVD mortality and rates of hospitalization due to CVD for Mediterranean part have been lower than rates for Croatia, while both rates for Continental part have been higher than rates for Croatia during entire period. This analysis identified the regions in which significant deviations from the general trend suggest the need for creation of a new national public health intervention model, focusing on changeable behaviour (lifestyles) risk factors.

Prevalence of increased body weight and hypertension in the population of Croatian mainland and Adriatic Islands--are islanders really healthier?

The aim of this study was to compare the prevalence of the hypertension and the increased body weight (BMI) between Croatian mainland and Adriatic island population. The data from the Croatian Adult Health Survey (N = 9,070) served as an estimate for the mainland Croatian population, while the data from "1001 Dalmatian study" (N = 1,001) were collected from four Adriatic islands; Rab, Vis, Lastovo and Mljet. The prevalence of increased body weight and hypertension was calculated for the four age groups and analyzed using chi-square test. The results indicate that men from the islands less frequently had normal body mass index (P < 0.001), and were more frequently overweight (P < 0.001). The prevalence of overweight and obesity were similar between the island and mainland women. The percent of normotensive respondents in men was significantly lower in islands (P < 0.001), while the prevalence of newly diagnosed hypertension was significantly higher among islanders in both genders (P < 0.001). Despite the traditionally prevalent Mediterranean diet and overall more favorable lifestyle islanders may not be as healthy as previously studies suggested, in terms of cardiovascular risk factors prevalence. This might be related to the poor access to health care and preventive measures or low interest for health care especially among men on the islands, reflected in the higher prevalence of newly diagnosed hypertension. These findings suggest that island populations represent good candidates for disease awareness programs and health promotion interventions.

Colorectal cancer in the Split-Dalmatia County.

Colorectal cancer was the second leading cause of cancer deaths in the Split-Dalmatia County during the 1993-2005 period. The primary aim of this study was to analyze recent trends in the mortality caused by colorectal cancer in the Split-Dalmatia County. Secondly, the aim was also to analyze data on colorectal cancer patients operated on at Split University Hospital Center according to sex, age, localization of cancer and Dukes staging, in the period from January 1, 2003 to December 31, 2004. The colorectal cancer death rate was found to be on an increase in both men and women; however, it was higher in men in both study years. The colorectal cancer death rate was also found to increase with age in both men and women. Analysis of data on patients operated on for colorectal cancer yielded a 2:1 male to female ratio. Analysis of histopathologic staging according to Dukes produced a statistically significant difference (P < 0.0001). Dukes B or C was diagnosed in 84.3% and Dukes A in 9.3% of cases. According to cancer localization, sigmoid colon and rectum were involved 1.8 times more frequently than other sites of the colon. The data obtained in this study indicated that only 9.3% of patients were treated in the early stage of disease (Dukes A), pointing to the need of organized medical examinations for early detection of colorectal cancer in order to reduce the mortality rate associated with the disease.

Efforts in fighting against cancer in Croatia have to be focused on the primary health care.

This manuscript is a comprehensive review of the long-lasting tradition and the state-of-the-art in the prevention and early detection of cancer in Croatia. Compared with other European countries, Croatia holds a high and unfavourable position in cancer morbidity and mortality. Global experience in implementation of national programmes for the early detection of cancer clearly shows that such approach is the most successful and in the long-term the least expensive method for fighting against cancer. In Croatia, numerous separate actions in cancer care have been taken, but never systematically, nor included in a health care policy. The National Programme for the Prevention and Early Detection of Cancer of the common localizations for which effective screening tests are available (breast, uterine cervix, colon and prostate) has recently been launched. Local long-standing experience of the Osijek-Baranja County in implementation of programmes of cancer care contributed significantly to these initiatives. In this review, draft National Programme and the early results of its implementation were presented. In addition, preparations for the research project "Model of early cancer detection integrated in a practice of family physician", recently set up by the Department of Family Medicine of the School of Medicine, University of Osijek, were described. In this project, the programme of the early detection of cancer in which family physicians take responsibility for the programme implementation is suggested. Possible advantages of this model, compared with the model proposed by the National Programme, centrally directed and mostly supplied by the public services, are pointed out.

Lymphohematopoietic malignancies and oil exploitation in Koprivnica-Krizevci County, Croatia.

To determine lymphohematopoietic malignancy incidence rates between populations living near oil-gas fields (two regions) compared with those living in areas free from oil-gas exploitation (one region) in Koprivnica-Krizevci County, Croatia, 803 new cases of lymphohematopoietic malignancies were studied for two time periods: 1971-1980 (prior to oil-gas exploitation) and 1981-2000 (during oil-gas exploitation). The results showed considerable geographic differences in the incidences of chronic myeloid leukemia and multiple myeloma. The authors conclude that proximity to oil or gas fields represents an increased population risk of developing lymphohematopoietic cancers.

Chromosome damage and cancer risk in the workplace: the example of cytogenetic surveillance in Croatia.

The use of cytogenetic assays in the surveillance of populations occupationally exposed to genotoxic carcinogens originates from the assumption that chromosomal alterations might be causally involved in early stages of carcinogenesis. Historical cohort studies have since 1990s consistently reported an association between the level of chromosomal aberrations (CA) in peripheral lymphocytes of healthy subjects and the risk of cancer. Only in few cases, have these results been transformed into a regulatory tool for improving occupational safety. The cytogenetic surveillance program adopted for more than two decades in the Republic of Croatia is one of these few examples. Croatian workers exposed to genotoxic agents were systematically screened for CA, to identify occupational settings needing a priority intervention. Significant increases of mean CA frequency were observed in groups exposed to ionizing radiation, chemical agents, and mixed exposures when compared with a group of unexposed referents. CA data on 736 men and 584 women, monitored between 1987 and 2000, have been associated with cancer incidence. Although the small size of the cohort did not allow for reaching statistical significance, the medium tertile of the CA frequency distribution was associated with a doubling of cancer incidence rate ratio (IRR=2.40; 95% CI 0.85-6.77) when compared with the lowest tertile. For chromosome-type CA, IRR was non-significantly increased for both the medium (IRR 1.53, 95% CI 0.58-3.99) and high categories (IRR 1.69; 95% CI 0.61-4.72). Recommendations for future strategies comprise the inclusion of predictive biomarkers in surveillance programs, the definition of a regulatory framework, and their possible use for the identification of individual risk profiles.

Role of insulin-like growth factor-1 in colon cancerogenesis: a case-control study.

BACKGROUND: Our aim was to establish whether individuals who developed colon cancer have elevated blood levels of insulin-like growth factor-1 (IGF-1). METHODS: This was a case/control study in which 52 patients with colon cancer and a corresponding control group were investigated. Data on age, weight, height, and sex of subjects were recorded and levels of IGF-1 and growth hormone, as well as insulin and C-peptide levels, were measured in the morning before eating, 90 min after breakfast and again 90 min after lunch. RESULTS: We found significantly higher levels of IGF-1 in blood of colon cancer patients compared to the control group. No differences in the levels of growth hormone, insulin and C-peptide in blood were found between colon cancer patients and the control group. It was found that the increase of IGF-1 level was followed by a 3.15-fold increased risk for developing colon cancer. There were no differences in the levels of IGF-1 in blood in all three measurements in the group of colon cancer patients, whereas differences were found in the control group. We found differences in the levels of insulin and C-peptide in blood in all three measurements in both groups of patients. No differences were found in the levels of growth hormone in blood in all three measurements in both groups of patients. CONCLUSIONS: The results of this study suggest a positive correlation between the increased levels of IGF-1 and colon cancer and are thus consistent with the hypothesis that the level of IGF-1 plays an important role in the development of colon cancer.

Cervical cancer in Croatia: state of the art and possibilities for prevention.

In Croatia, there are about 355 incident cases and about 100 deaths from cervical cancer every year. The aim of this study is to present the trends of cervical cancer incidence and mortality and to propose preventive strategies for cervical cancer in Croatia. Age-standardised and age-specific cervical cancer incidence rates were calculated for the period 1985-2004. For cervical cancer mortality data, the WHO Mortality Database was used. After an early decrease of cervical cancer incidence and mortality following the introduction of opportunistic screening in Croatia, no further decrease has been observed since the 1990s. An increase in incidence over the last 20 years was observed in the age-groups 40-44 and 45-49 years. To reduce cervical cancer rates, an organised cervical cancer screening programme is essential. In addition, HPV vaccination should be introduced in the school vaccination programme to achieve further reductions in cervical cancer incidence in the future.

Acute coronary syndrome frequency in western Herzegovina over the fifteen year period (1987-2001).

All patients who suffered from the acute coronary syndrome in western Herzegovina over the fifteen year period (1987-2001) are included in this retrospective epidemiological study. The population that was undertaken by the study is relative stabile and did not emigrate during the war period. The study compared the time before the war (1987-1991), during the war (1992-1996) and after the war (1997-2001). The data were acquired from the archives of the patients of the Mostar hospital and Clinical hospital Split during the war period. A total of 2022 acute coronary syndrome patients were found, 1305 men and 717 women. More patients were treated during the war compared to the time before the war for both male and female patients (p<0.0005). During the after-war period the number of treated patients was greater (p< 0.0005) compared to the war-time for both sexes. The comparison of the after-war period and the pre-war period reveals a statistically significant difference as the number of treated patients (male and female) is larger in the after-war period. The number of patient who are 65 years old and older than that is greater, and that is statistically significant (p= 0.0005.). We can conclude that the stress caused by the war and other factors have influenced a larger number of treated patients of acute coronary syndrome. Therefore, further epidemiological researches of acute coronary syndrome with the accent on prevention and treatment are needed.

Present state and possibilities for improvement of cancer prevention and early detection in the Osijek-Baranya county.

Cancer morbidity and mortality are on a steady increase in Croatia. Technologic possibilities for appropriate management are available for four cancer sites, i.e. cancer of the breast, cervix uteri, colorectum and prostate, and include cancer prevention and early detection in individuals yet free from manifest signs of the disease. The magnitude of the problem, the experience acquired to date, health care personnel available, and additional resources required to launch a systematic program of early detection of the disease are presented. The program should be initially launched in a county with greatest experience in early detection of cancer, where health care service is ready to immediately start its implementation. The role of family physician, gynecologic service at primary health care level, and polyclinic-consultation hospital service in program implementation is described. The following three possible options for early detection of cancer are analyzed and proposed: minimal program (early detection every 3 years), medium program (the same individuals examined every 2 years), and optimal program proposed by the American Cancer Society and other national and international organizations.

[Informatics in the Croatian health care system]. / Informatizacija Hrvatskog zdravstva.

Informatization process of the Croatian health care system started relatively early. Computer processing of data of persons not covered by health insurance started in 1968 in Zagreb. Remetinec Health Center served as a model of computer data processing (CDP) in primary health care and Sveti Duh General Hospital in inpatient CDP, whereas hospital administration and health service were first introduced to Zagreb University Hospital Center and Sestre Milosrdnice University Hospital. At Varazdin Medical Center CDP for health care services started in 1970. Several registries of chronic diseases have been established: cancer, psychosis, alcoholism, and hospital registries as well as pilot registries of lung tuberculosis patients and diabetics. Health statistics reports on healthcare services, work accidents and sick-leaves as well as on hospital mortality started to be produced by CDP in 1977. Besides alphanumeric data, the modern information technology (IT) can give digital images and signals. Communication in health care system demands a standardized format of all information, especially for telemedicine. In 2000, Technical Committee for Standardization in Medical Informatics was founded in Croatia, in order to monitor the activities of the International Standardization Organization (ISO) and Comite Européen de Normalisation (CEN), and to implement their international standards in the Croatian standardization procedure. The HL7 Croatia has also been founded to monitor developments in the communication standard HL7. So far, the Republic of Croatia has a number of acts regulating informatization in general and consequently the informatization of the health care system (Act on Personal Data Confidentiality, Act on Digital Signature, Act of Standardization) enacted. The ethical aspect of data security and data protection has been covered by the Code of Ethics for medical informaticians. It has been established by the International Medical Informatics Association (IMIA), and the Croatian Society of Medical Informatics (CSMI) has translated it into Croatian and published it on its website. Based on a survey of medical staff attitudes toward health care system informatization, the Croatian health system appears to be ready for informatization. The only requirement is that the present and future health care providers have appropriate medical informatics education, proper computer equipment at their workplace, and an opportunity to participate in the development and/or improvement of the health information system. One of the EU health strategy priorities is the improvement of health information and knowledge. It means that integrated health information systems are required, i.e. systems able to provide key information on health and health care system to the politicians, health professionals and public in general.

[Role of standardization in health care system computerization]. / Uloga normizacije u informatizaciji zdravstva.

Standardization system includes development, publishing and promotion of standards, as well as their use in practice. Products, services and processes in a variety of human activities should be standardized. The goal of standardization is to achieve a high security level, a high quality, usefulness and effectiveness as well as limitation of variability, ensuring compatibility and replacement (of products), and to eliminate technical problems in the international exchange of people, work, products and services. The leading areas/objects of standardization in medical informatics are electronic health record, classification in health care, communication and message exchange as well as data security and protection of the whole health information system. Technical Committee for Standardization in Medical Informatics (TC215) has so far accepted fifteen standards and prestandards. The affiliate HL7 Croatia works on localization of communication standard HL7 and adaptation to the Croatian requirements.