Worldwide trends in esophageal cancer survival, by sub-site, morphology, and sex: an analysis of 696,974 adults diagnosed in 60 countries during 2000-2014 (CONCORD-3).

BACKGROUND: Esophageal cancer survival is poor worldwide, though there is some variation. Differences in the distribution of anatomical sub-site and morphological sub-type may help explain international differences in survival for all esophageal cancers combined. We estimated survival by anatomic sub-site and morphological sub-type to understand further the impact of topography and morphology on international comparisons of esophageal cancer survival. METHODS: We estimated age-standardized one-year and five-year net survival among adults (15-99 years) diagnosed with esophageal cancer in each of 60 participating countries to monitor survival trends by calendar period of diagnosis (2000-2004, 2005-2009, 2010-2014), sub-site, morphology, and sex. RESULTS: For adults diagnosed during 2010-2014, tumors in the lower third of the esophagus were the most common, followed by tumors of overlapping sub-site and sub-site not otherwise specified. The proportion of squamous cell carcinomas diagnosed during 2010-2014 was generally higher in Asian countries (50%-90%), while adenocarcinomas were more common in Europe, North America and Oceania (50%-60%). From 2000-2004 to 2010-2014, the proportion of squamous cell carcinoma generally decreased, and the proportion of adenocarcinoma increased. Over time, there were few improvements in age-standardized five-year survival for each sub-site. Age-standardized one-year survival was highest in Japan for both squamous cell carcinoma (67.7%) and adenocarcinoma (69.0%), ranging between 20%-60% in most other countries. Age-standardized five-year survival from squamous cell carcinoma and adenocarcinoma was similar for most countries included, around 15%-20% for adults diagnosed during 2010-2014, though international variation was wider for squamous cell carcinoma. In most countries, survival for both squamous cell carcinoma and adenocarcinoma increased by less than 5% between 2000-2004 and 2010-2014. CONCLUSIONS: Esophageal cancer survival remains poor in many countries. The distributions of sub-site and morphological sub-type vary between countries, but these differences do not fully explain international variation in esophageal cancer survival.

Epidemiology of vulvar cancer in Croatia.

AIM: To assess the incidence and mortality trends of invasive vulvar cancer in Croatia between 2001 and 2019/2020. METHODS: The incidence data for the period 2001-2019 were obtained from the Croatian National Cancer Registry. The number of deaths from invasive vulvar cancer by age groups between 2001 and 2020 was obtained from the Croatian Bureau of Statistics. Joinpoint regression analysis was used to assess the trends and trend changes. RESULTS: Joinpoint regression analysis of vulvar cancer incidence rate showed a non-significant average annual percent increase (APC) of 0.8 (95% confidence interval [CI]=-0.3-2.0) during the whole period. There was also a non-significant increase in women under 60, with an average APC of 1.0 (CI = -1.6-3.7) during the whole period; similar results were obtained in women over 60 years of age (APC=0.9; CI=-0.3-2.1). The average annual percent increase in vulvar cancer mortality rate was 0.2% (CI = -1.0-1.5), with a similar trend in women over 60 years of age (APC=0.1; CI=-1.3-1.5). Mortality in women under 60 years of age was not assessed due to a very small number of deaths observed in the study period. CONCLUSION: In the studied period, the incidence of invasive vulvar cancer in Croatia was stable. Age-standardized rates (for all-ages, under 60, and over 60 years of age) increased, but the increase did not reach the level of statistical significance. The pattern in younger and older age groups was the same. The mortality rates over the last decade were stable.

KIDNEY CANCER IN CROATIA - TRENDS IN INCIDENCE AND MORTALITY IN THE 21ST CENTURY.

Kidney cancer is estimated to be responsible for more than 400 000 new cancer cases and 180 000 cancer deaths a year. Its incidence is increasing in the majority of developed countries, due to an increased prevalence of recognized risk factors such as smoking, alcohol use and obesity, as well as incidental findings on unrelated diagnostic imaging procedures. Mortality is decreasing in the majority of European countries, due to improvements in treatment and stage at diagnosis shift with more tumors being diagnosed at an early stage. In this paper, we present kidney cancer incidence and mortality trends in Croatia using joinpoint regression analysis. The incidence was rising throughout the 2001-2019 period, with an annual percent change (APC) of 2.5%; more so in men (APC of 2.5%) than in women (APC of 2.2%). Mortality increased during the 2001-2014 period (APC of 2.4%), but started to decrease in recent years (APC -2.7%, 2014-2020). Unlike sex differences observed in other European countries, with more favorable mortality trends found in women, our study showed a constant increase in mortality in women (APC of 1.2%) and a recent decrease in mortality in men, starting in 2013 (APC of -2.8%), after a period of increase from 2001 (APC of 3.3%).

ARSENIC IN DRINKING WATER AND URINE AND ITS RELATIONSHIP WITH MALIGNANT TUMORS OF URINARY TRACT IN OSIJEK-BARANJA COUNTY, CROATIA.

Increased values of arsenic in potable water in eastern Croatia has been a matter of scientific interest for the past two decades due to numerous health effects, including carcinogenic ones. This study investigated whether prolonged exposure to increased arsenic from water could be detectable through increased arsenic in urine, and whether it influenced the incidence of kidney and bladder cancer in Osijek-Baranja County. Inductively coupled plasma mass spectrometry (ICP-MS) was used for analysis of water samples from available water sources (wells, aqueducts). In addition, examinees from Osijek, Nasice, Vladislavci, Cepin and Dalj gave their urine samples for analysis. Data on cancer incidence were obtained from the Institute for Public Health Registry and cumulative incidence of kidney and bladder cancer was calculated for the period between January 1, 2000 and December 31, 2018. Elevated arsenic concentration in drinking water was recorded in Vladislavci, Cepin and Osijek area with values above the allowed maximum according to the EU standards (10 µg L-1) and as a result, arsenic levels in urine of the inhabitants were also elevated. Cumulative incidence for bladder cancer showed correlation between increased arsenic in water and urine in the areas affected by increased arsenic in water. Epidemiologic data suggest a conclusion that elevated arsenic could be considered at least as a cofounding factor for urinary tract cancer.

Does the morphology of cutaneous melanoma help to explain the international differences in survival? Results from 1 578 482 adults diagnosed during 2000-2014 in 59 countries (CONCORD-3).

BACKGROUND: CONCORD-3 highlighted wide disparities in population-based 5-year net survival for cutaneous melanoma during 2000-2014. Clinical evidence suggests marked international differences in the proportion of lethal acral and nodular subtypes of cutaneous melanoma. OBJECTIVES: We aimed to assess whether the differences in morphology may explain global variation in survival. METHODS: Patients with melanoma were grouped into the following seven morphological categories: malignant melanoma, not otherwise specified (International Classification of Diseases for Oncology, third revision morphology code 8720), superficial spreading melanoma (8743), lentigo maligna melanoma (8742), nodular melanoma (8721), acral lentiginous melanoma (8744), desmoplastic melanoma (8745) and other morphologies (8722-8723, 8726-8727, 8730, 8740-8741, 8746, 8761, 8770-8774, 8780). We estimated net survival using the nonparametric Pohar Perme estimator, correcting for background mortality by single year of age, sex and calendar year in each country or region. All-ages survival estimates were standardized using the International Cancer Survival Standard weights. We fitted a flexible parametric model to estimate the effect of morphology on the hazard of death. RESULTS: Worldwide, the proportion of nodular melanoma ranged between 7% and 13%. Acral lentiginous melanoma accounted for less than 2% of all registrations but was more common in Asia (6%) and Central and South America (7%). Overall, 36% of tumours were classified as superficial spreading melanoma. During 2010-2014, age-standardized 5-year net survival for superficial spreading melanoma was 95% or higher in Oceania, North America and most European countries, but was only 71% in Taiwan. Survival for acral lentiginous melanoma ranged between 66% and 95%. Nodular melanoma had the poorest prognosis in all countries. The multivariable analysis of data from registries with complete information on stage and morphology found that sex, age and stage at diagnosis only partially explain the higher risk of death for nodular and acral lentiginous subtypes. CONCLUSIONS: This study provides the broadest picture of distribution and population-based survival trends for the main morphological subtypes of cutaneous melanoma in 59 countries. The poorer prognosis for nodular and acral lentiginous melanomas, more frequent in Asia and Latin America, suggests the need for health policies aimed at specific populations to improve awareness, early diagnosis and access to treatment. What is already known about this topic? The histopathological features of cutaneous melanoma vary markedly worldwide. The proportion of melanomas with the more aggressive acral lentiginous or nodular histological subtypes is higher in populations with predominantly dark skin than in populations with predominantly fair skin. What does this study add? We aimed to assess the extent to which these differences in morphology may explain international variation in survival when all histological subtypes are combined. This study provides, for the first time, international comparisons of population-based survival at 5 years for the main histological subtypes of melanoma for over 1.5 million adults diagnosed during 2000-2014. This study highlights the less favourable distribution of histological subtypes in Asia and Central and South America, and the poorer prognosis for nodular and acral lentiginous melanomas. We found that later stage at diagnosis does not fully explain the higher excess risk of death for nodular and acral lentiginous melanoma compared with superficial spreading melanoma.

THE ROLE OF SALIVARY AND SERUM CA125 AND ROUTINE BLOOD TESTS IN PATIENTS WITH OVARIAN MALIGNANCIES.

The use of routine blood tests has recently been shown to be promising in determining disease-free and overall survival in patients with various malignancies, and also in gynecologic malignancies. The aim of this study was to evaluate whether salivary and serum CA125 levels correlate and whether salivary and serum CA125, C-reactive protein and routine blood tests might serve as a prognostic factor in malignant ovarian tumors, and whether they might differentiate between benign and malignant ovarian tumors. A total of 98 women were included (48 with benign ovarian tumors and 50 with malignant ovarian tumors), in whom routine blood tests were made and salivary and serum CA125 levels were determined by use of ELISA. Increase in serum CA125 and amylase decreased overall survival, whereas increase in salivary CA125, potassium levels and hemoglobin increased overall survival. Significant correlation of serum CA125 and C-reactive protein was found in the group with malignant tumors. In conclusion, significant increase in the levels of serum CA125 and amylase correlated with decreased survival, whereas increased salivary CA125, hemoglobin and potassium levels significantly correlated with increased survival.

100 Years apart: Psychiatric admissions during Spanish flu and COVID-19 pandemic.

The last pandemic comparable to the current COVID-19 pandemic was the Spanish flu. Using the admission record books for the years 1917 and 1918 and electronic health records for the years 2019 and 2020, we extracted the relevant data and explored how they affected the numbers of emergency psychiatric admissions. The general trend in both pandemics was that they did not cause a rise in psychiatric admissions, findings which go along with reports around Europe. The causes for these similarities are complex but provide an interesting perspective as to why there is no concurrent rise in emergency psychiatric admissions.

Is it too expensive to fight cancer? Analysis of incremental costs and benefits of the Croatian National Plan Against Cancer.

This cost-effectiveness study analyses the expected impacts of activities proposed by the Croatian National Plan Against Cancer (NPAC) on cancer incidence and survival rates, as related to their respective costs. We evaluated the impact of the NPAC on two main outcomes, namely, reduced incidence and the improved survival of cancer patients, expressed as life years gained (LYGs), which enabled the calculation of incremental cost-effectiveness ratios (ICERs) in the form of cost per LYG. In the analysis of costs, we considered both the direct costs of NPAC activities as well as the wider indirect societal costs of cancer, thus permitting the calculation of the ICER both from the narrower national health insurer's perspective (accounting only for the direct costs) and the wider societal perspective (accounting both for the direct and indirect costs). We estimated that on average, for all patients benefiting from the implementation of the NPAC in Croatia, an additional LYG would be yielded at the additional cost of €1.021 (societal perspective). The NPAC can, for some sites, even be considered a dominant intervention due to the negative cost/LYG ratio, meaning that it generates additional LYGs while at the same time, reducing total societal costs. Taking a narrower health insurer's perspective (i.e., accounting only for the direct costs), the NPAC produces an additional LYG at an additional cost of €1.408. Both cost per LYG estimates can be considered cost-effective investment options.

Do Athletes Practicing Outdoors Know and Care Enough About the Importance of Photoprotection?

Athletes practicing and competing outdoors are exposed to considerable UV radiation and at an increased risk for the development of UV-related skin conditions, including skin cancer. Risk factors for skin cancer include genetics, immune status, and particularly UV radiation. Independent factors, such as phototype, family or personal history of melanoma, number of nevi, atypical nevi and solar lentigines, as well as sunburn history are also important risk indicators for skin cancer, especially melanoma (1-3). Additionally, exercise-induced immunosuppression may contribute to the development of skin cancers (4). To the best of our knowledge, only one article has been previously published analyzing the effects of UV exposure in triathlon athletes (5). Our aim was to analyze sun protection habits of athletes competing in the Croatian Olympic and Super Sprint triathlon and screen them for skin cancer and other skin lesions. Participants completed a questionnaire consisting of questions regarding personal and family history, phenotypic characteristics, training habits, and sunlight-related risk factors. Additionally, a total body skin examination was performed by a board-certified dermatologist. Skin type, number of melanocytic nevi, presence of atypical nevi, solar lentigines, as well as suspicious lesions were recorded (Figure 1). The study population consisted of 95 participants, 65 (68%) men and 30 (32%) women. Approximately 30% of participants spent 4 to 6 hours per week outdoors, while 21% spent more than 10 hours outdoors per week. Regarding sun protection habits, more than 90% of participants stated it was important to use sunscreen, however, almost 50% rarely used sunscreen while training, 27% frequently used sunscreen, while only 3% always used sunscreen. A staggering 20% of participants never used sunscreen. Unsurprisingly, almost a third of the athletes (26%) reported previously having severe sunburns with blisters. Almost 10% reported a positive family history of melanoma and one reported positive personal history of melanoma. Skin examinations revealed that nearly half of the participants (46%) had solar lentigines, 25% had atypical nevi, while 2 participants presented with actinically damaged skin and 2 participants with actinic keratoses. The majority of the triathletes (around 57%) had less than 20 nevi on their skin, while only around 10% had between 50 and 100 nevi. No lesions that were suggestive of invasive skin cancer - non-melanoma skin cancer or melanoma - were identified. UV exposure is usually exceeded in most activities performed outdoors with exposed skin, even if they are performed in sunny conditions for only a short amount of time. The limit for UV exposure was exceeded more than 30 times during the Ironman Triathlon World Championship 1999 in Hawaii, as reported by Moehrle. Additionally, despite the application of water-resistant sunscreen (SPF 25+), these triathletes showed sunburn on sun-exposed skin, which was most probably due to water exposure, sweating, and friction (5). Other studies evaluating skin cancer and sun protection habits of outdoor athletes indicate that most do not appear to be aware of the serious potential health risks of extensive sun exposure (6-8). Even though no invasive skin cancer was detected in our athletes, a significant number of participants presented with solar lentigines and a fair amount with atypical nevi, both considered risk factors for skin cancer. Additionally, a large proportion of participants had a history of severe blistering sunburns, which is not surprising given that 20% never use sunscreen. Our results indicate that it is necessary to advise and educate outdoor athletes about sun-smart behavior. Avoiding training and competing in periods with high sun exposure, wearing adequate clothing, and applying water-resistant high-protection sunscreen regularly and sufficiently are practices and habits that should be encouraged. Screening for skin cancer is a valuable measure and should be performed in high-risk individuals such as triathletes.

Trend analyses of breast cancer incidence and mortality in Vojvodina.

PURPOSE: Breast cancer is the most common type of malignant tumor in women and one of the most significant public health problems in the world. The purpose of this work was to determine breast cancer epidemiology in the Autonomous Province of Vojvodina in a 20-year period (1993 to 2012) by determining breast cancer incidence and mortality in female population and analyzing the trend in the specified period. METHODS: The research involved the population of women in Vojvodina in the period from 1993 to 2012. Data were obtained from the Register for malignant neoplasms of Vojvodina. Incidence and mortality trends were analyzed by a joinpoint regression analysis. RESULTS: A total of 20,242 cases of breast cancer were registered in the observed period. Standardized incidence ratio in 2012 was 71.2/100,000. The trend of incidence increased with an average annual percentage of growth of 2.10. A total 10,062 deaths due to breast cancer were documented. Standardized incidence ratio in 2012 was 28.6/100,000. An increase of mortality rate by 1.70% per year was recorded in the period from 1992 to 2006 and a decline in the mortality rate by 1.56% was noticed afterwards. The highest percentage of deaths due to breast cancer was recorded in a group aged 60-69 years (26.7%).

Changes in disease burden in Poland between 1990-2017 in comparison with other Central European countries: A systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: Systematic collection of mortality/morbidity data over time is crucial for monitoring trends in population health, developing health policies, assessing the impact of health programs. In Poland, a comprehensive analysis describing trends in disease burden for major conditions has never been published. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides data on the burden of over 300 diseases in 195 countries since 1990. We used the GBD database to undertake an assessment of disease burden in Poland, evaluate changes in population health between 1990-2017, and compare Poland with other Central European (CE) countries. METHODS: The results of GBD 2017 for 1990 and 2017 for Poland and CE were used to assess rates and trends in years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life years (DALYs). Data came from cause-of-death registration systems, population health surveys, disease registries, hospitalization databases, and the scientific literature. Analytical approaches have been used to adjust for missing data, errors in cause-of-death certification, and differences in data collection methodology. Main estimation strategies were ensemble modelling for mortality and Bayesian meta-regression for disability. RESULTS: Between 1990-2017, age-standardized YLL rates for all causes declined in Poland by 46.0% (95% UI: 43.7-48.2), YLD rates declined by 4.0% (4.2-4.9), DALY rates by 31.7% (29.2-34.4). For both YLLs and YLDs, greater relative declines were observed for females. There was a large decrease in communicable, maternal, neonatal, and nutritional disease DALYs (48.2%; 46.3-50.4). DALYs due to non-communicable diseases (NCDs) decreased slightly (2.0%; 0.1-4.6). In 2017, Poland performed better than CE as a whole (ranked fourth for YLLs, sixth for YLDs, and fifth for DALYs) and achieved greater reductions in YLLs and DALYs than most CE countries. In 2017 and 1990, the leading cause of YLLs and DALYs in Poland and CE was ischaemic heart disease (IHD), and the leading cause of YLDs was low back pain. In 2017, the top 20 causes of YLLs and YLDs in Poland and CE were the same, although in different order. In Poland, age-standardized DALYs from neonatal causes, other cardiovascular and circulatory diseases, and road injuries declined substantially between 1990-2017, while alcohol use disorders and chronic liver diseases increased. The highest observed-to-expected ratios were seen for alcohol use disorders for YLLs, neonatal sepsis for YLDs, and falls for DALYs (3.21, 2.65, and 2.03, respectively). CONCLUSIONS: There was relatively little geographical variation in premature death and disability in CE in 2017, although some between-country differences existed. Health in Poland has been improving since 1990; in 2017 Poland outperformed CE as a whole for YLLs, YLDs, and DALYs. While the health gap between Poland and Western Europe has diminished, it remains substantial. The shift to NCDs and chronic disability, together with marked between-gender health inequalities, poses a challenge for the Polish health-care system. IHD is still the leading cause of disease burden in Poland, but DALYs from IHD are declining. To further reduce disease burden, an integrated response focused on NCDs and population groups with disproportionally high burden is needed.

Birth seasonality of childhood central nervous system tumors: Analysis of primary data from 16 Southern-Eastern European population-based registries.

Season of birth, a surrogate of seasonal variation of environmental exposures, has been associated with increased risk of several cancers. In the context of a Southern-Eastern Europe (SEE) consortium, we explored the potential association of birth seasonality with childhood (0-14 years) central nervous system (CNS) tumors. Primary CNS tumor cases (n = 6,014) were retrieved from 16 population-based SEE registries (1983-2015). Poisson regression and meta-analyses on birth season were performed in nine countries with available live birth data (n = 4,987). Subanalyses by birth month, age, gender and principal histology were also conducted. Children born during winter were at a slightly increased risk of developing a CNS tumor overall [incidence rate ratio (IRR): 1.06, 95% confidence intervals (CI): 0.99-1.14], and of embryonal histology specifically (IRR: 1.13, 95% CI: 1.01-1.27). The winter peak of embryonal tumors was higher among boys (IRR: 1.24, 95% CI: 1.05-1.46), especially during the first 4 years of life (IRR: 1.33, 95% CI: 1.03-1.71). In contrast, boys <5 years born during summer seemed to be at a lower risk of embryonal tumors (IRR: 0.73, 95% CI: 0.54-0.99). A clustering of astrocytomas was also found among girls (0-14 years) born during spring (IRR: 1.23, 95% CI: 1.03-1.46). Although the present exploratory results are by no means definitive, they provide some indications for age-, gender- and histology-related seasonal variations of CNS tumors. Expansion of registration and linkage with cytogenetic reports could refine if birth seasonality is causally associated with CNS tumors and shed light into the complex pathophysiology of this lethal disease.

Prevalence of somatic comorbidities among coronavirus disease 2019 patients in Croatia in the first pandemic wave: data from national public health databases.

AIM: To determine the prevalence of common somatic comorbidities among coronavirus disease 2019 (COVID-19) positive patients in Croatia in the first pandemic wave, and assess the differences in clinical outcomes depending on the presence of comorbidities. METHODS: We analyzed data from patients confirmed to be SARS-CoV-2-positive from February through May 2020. The data were obtained from clinical laboratories, primary health care providers, and hospitals. Previously recorded comorbidities, including diabetes, cancer, circulatory diseases, chronic pulmonary, and kidney disease, were analyzed. RESULTS: Among 2249 patients, 46.0% were men (median age 51 years; median disease duration 27 days). Hospitalization was required for 41.8% patients, mechanical ventilation for 2.5%, while 4.7% of all patients died. Patients who died were significantly older (median 82 vs 50 years, P<0.001) with a higher prevalence of all investigated comorbidities (all p's <0.001), more frequently required mechanical ventilation (34% vs 1%, P<0.001), and had shorter length of hospital stay (median 13 vs 27 days, P<0.001) with no sex preponderance. Patients requiring mechanical ventilation were significantly older (median age 70 vs 51 years, P<0.001), more frequently men (59.6% vs 45.7%, P=0.037), showed a higher prevalence of all comorbidities except ischemic heart and chronic kidney disease (all p's <0.001), and demonstrated a higher case-fatality rate (63.2% vs 3.2%, P<0.001). CONCLUSION: COVID-19 patients who died in the first pandemic wave in Croatia were more likely to suffer previous somatic comorbidities. This corroborates the findings of similar studies and calls for further research into the underlying disease mechanisms, hence providing ground for more efficient preventive measures.

Malignant brain neoplasms incidence and mortality trends in Croatia from 2001 to 2014.

AIM: To analyze the sex-specific incidence and mortality trends of brain malignancies in Croatia from 2001 to 2014. METHODS: Incidence and mortality rates per 100000 population were calculated using data obtained from the Croatian National Cancer Registry and the Croatian Bureau of Statistics. Rates were age-standardized to the European Standard Population, and trends were assessed using joinpoint regression. RESULTS: In the observed period there were 6634 new brain malignancy cases (52% men) and 5379 deaths due to this diagnosis (52% men). Age-standardized incidence rates ranged from 9.2-11.5 per 100000 in men and from 7-8.8 per 100000 in women. Mortality rates ranged from 7.5-8.7 per 100 000 in men and from 5-6.5 in women. Incidence trends in men, mortality in men, and mortality in women were not statistically significant, while a significant trend was observed in incidence in women (annual percent change -1.5; 95% confidence interval -2.3 to -0.6). No joinpoints were observed in any of the joinpoint analyses by sex for incidence and mortality. Age-specific incidence and mortality rates in both sexes indicate a trend shift toward older age. The proportion of morphologically verified cases ranged from 40.2%-62.4% in men and from 38.6%-56.3% in women; the proportion of death-certificate-only cases ranged from 3.3%-9.4% in men and from 3.3%-17.5% in women. CONCLUSION: Incidence and mortality of brain malignancies in Croatia are among the highest in Europe, while reporting on brain malignancies is still poor. There is a need for improved care of patients with brain malignancies and detailed and accurate data reporting.

HPV-driven oropharyngeal squamous cell cancer in Croatia - Demography and survival.

OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Main HNSCC risk factors are tobacco, alcohol, and high-risk human papillomavirus (HPV). HPV+ oropharyngeal squamous cell cancer (OPSCC) usually have different etiology, increasing incidence and often show an improved survival when compared to HPV-negative cases. The objective of the current study was to retrospectively examine the influence of HPV on the survival of OPSCC patients in a non-Western population setting. MATERIALS AND METHODS: We determined the presence of HPV DNA and/or RNA in 99 formalin-fixed paraffin embedded (FFPE) tissue samples of OPSCC patients treated between 2002 and 2015. Patients were compared based on laboratory, demographic, clinical, life style characteristics and survival. RESULTS: HPV RNA was found in 29.3% cases. However, groups based on HPV data (either RNA, DNA or retrospectively collected p16 staining) did not show significant differences. Overall, 5-year survival was 30% with minimal influence of the HPV positivity. CONCLUSIONS: The HPV influence on survival of OPSCC patients is not identical between populations probably due to other factors overshadowing the HPV effect. This should be taken into account when treatment or policy decisions are made in each particular setting.

Overdose mortality rates in Croatia and factors associated with self-reported drug overdose among persons who inject drugs in three Croatian cities.

BACKGROUND: Drug overdose is the major cause of morbidity and mortality among persons who inject drugs (PWID). We assessed factors associated with the non-fatal drug overdose among PWID in three Croatian cities and national trends of overdose-related mortality (OM), and rates of uptake of opioid agonist drug treatment (OAT). METHODS: We used a respondent-driven sampling method to recruit 830 PWID in Zagreb, Split and Rijeka in 2014/2015. Participants completed behavioural questionnaires that included questions about overdose history, and we used Poisson regression to assess factors associated with self-reported overdose. We used joinpoint regression to calculate national trends of OM from 2001 to 2015 and rates of uptake of drug treatment from 2005 to 2015. RESULTS: Lifetime prevalence of self-reported drug overdose in our RDS sample was 45.2%, while 4.1% of PWID reported overdose in the past 12 months; PWID who injected more than one type of drug in the past 12 months (adjusted prevalence ratio [aPR] = 4.56, 95% confidence intervals [CI] = 1.35-15.38) compared to injecting only heroin, and those enrolled in OAT (aPR = 1.94, 95% CI = 1.01-3.74) were more likely to report overdose in the past 12 months. We observed an increase in annual percent change (APC) of the national OM rates from 2001 to 2007 (APC = 22.5%, 95% CI = 16.3-29.0) and a decline from 2007 to 2015 (APC = -8.0%, 95% CI = -5.3- -10.5). The national rates of drug treatment enrollment increased from 2005 to 2010 (APC = 12.0%, 95% CI = 10.3-13.8), mostly due to increase in provision of buprenorphine from 2005 to 2008 (APC = 130.4%, 95% CI = 102.1-162.7). CONCLUSION: Injecting more than one type of drugs and enrollment in OAT while still injecting drugs was positively associated with non-fatal overdose in our sample. To further reduce OM in Croatia we suggest improvements in coverage and delivery of OAT and establishment of provision of naloxone for PWID.

Plasma Fucosylated Glycans and C-Reactive Protein as Biomarkers of HNF1A-MODY in Young Adult-Onset Nonautoimmune Diabetes.

OBJECTIVE: Maturity-onset diabetes of the young (MODY) due to variants in HNF1A is the most common type of monogenic diabetes. Frequent misdiagnosis results in missed opportunity to use sulfonylureas as first-line treatment. A nongenetic biomarker could improve selection of subjects for genetic testing and increase diagnosis rates. We previously reported that plasma levels of antennary fucosylated N-glycans and high-sensitivity C-reactive protein (hs-CRP) are reduced in individuals with HNF1A-MODY. In this study, we examined the potential use of N-glycans and hs-CRP in discriminating individuals with damaging HNF1A alleles from those without HNF1A variants in an unselected population of young adults with nonautoimmune diabetes. RESEARCH DESIGN AND METHODS: We analyzed the plasma N-glycan profile, measured hs-CRP, and sequenced HNF1A in 989 individuals with diabetes diagnosed when younger than age 45, persistent endogenous insulin production, and absence of pancreatic autoimmunity. Systematic assessment of rare HNF1A variants was performed. RESULTS: We identified 29 individuals harboring 25 rare HNF1A alleles, of which 3 were novel, and 12 (in 16 probands) were considered pathogenic. Antennary fucosylated N-glycans and hs-CRP were able to differentiate subjects with damaging HNF1A alleles from those without rare HNF1A alleles. Glycan GP30 had a receiver operating characteristic curve area under the curve (AUC) of 0.90 (88% sensitivity, 80% specificity, cutoff 0.70%), whereas hs-CRP had an AUC of 0.83 (88% sensitivity, 69% specificity, cutoff 0.81 mg/L). CONCLUSIONS: Half of rare HNF1A sequence variants do not cause MODY. N-glycan profile and hs-CRP could both be used as tools, alone or as adjuncts to existing pathways, for identifying individuals at high risk of carrying a damaging HNF1A allele.

Epidemiology of Prostate Cancer in Croatia - Situation and Perspectives.

Prostate cancer represents a significant public health burden in Croatia, as well as in other developed countries. The aim of this paper was to present the current epidemiological situation in Croatia in comparison to other similar countries, using basic indicators such as incidence, mortality, prevalence and survival, and to discuss future possibilities in this field. The incidence of prostate cancer in Croatia has been rapidly increasing since the mid-nineties; recent data indicates that the trend is levelling off. Mortality data show constant increase since the 1960s, but mortality trends seem to be stabilizing in the recent period; however, Croatia is still in the top ten countries regarding prostate cancer mortality in Europe. Five-year prevalence in 2012 was estimated at 7,592 cases (426.7/100,000), ranking Croatia in the middle of European countries in the GLOBOCAN 2012 database. According to the CONCORD-2 study, five-year net survival in Croatia in the 2005-2009 period was 75.1%, which is lower than in similar European countries. The epidemiological pattern of prostate cancer in Croatia indicates a relatively low incidence, with significant room for improvement in mortality and survival data. Given the recent discussions regarding prostate cancer screening modalities, a debate is warranted and should be encouraged regarding the role of PSA testing in Croatia.

Survival and mortality rates of Wilms tumour in Southern and Eastern European countries: Socioeconomic differentials compared with the United States of America.

BACKGROUND: Despite recent therapeutic advancements, Wilms tumour (WT) presents remarkable survival variations. We explored mortality and survival patterns for children (0-14 years) with WT in 12 Southern and Eastern European (SEE) countries in comparison with the United States of America (USA). METHODS: A total of 3966 WT cases (0-14 years) were registered by a network of SEE childhood cancer registries (N:1723) during available registration periods circa 1990-2016 and surveillance, epidemiology, and end results program (SEER) (N:2243; 1990-2012); mortality data were provided by the respective national statistical services. Kaplan-Meier curves and Cox proportional hazards models were used to assess the role of age, sex, year of diagnosis, urbanisation and Human Development Index (HDI) on overall survival (OS). RESULTS: Persisting regional variations shape an overall 78% 5-year OS in the participating SEE countries, lagging behind the USA figure (92%, p=0.001) and also reflected by higher SEE mortality rates. Worth mentioning is the gradually escalating OS in SEE (hazard ratio [HR]5-year increment:0.67, 95% confidence interval [CI]:0.60, 0.75) vs. a non-significant 10% improvement in the SEER data, which had a high starting value. OS differentials [two-fold less favourable among children aged 10-14 years, boys and those living in rural SEE areas (HR:1.37; CI:1.10-1.71) or countries with inferior HDI (2-3-fold)] were minimal in the USA. CONCLUSIONS: Children with WT residing in SEE countries do not equally enjoy the substantial survival gains, especially for those living in rural areas and in lower HDI countries. Noteworthy are steep and sizeable survival gains in SEE along with the newly presented Greek data pointing to achievable survival goals in SEE despite the financial crisis.

Maturity onset diabetes of the young due to HNF1A variants in Croatia.

INTRODUCTION: Maturity onset diabetes of the young due to HNF1A mutations (HNF1A-MODY) is the most frequent form of monogenic diabetes in adults. It is often misdiagnosed as type 1 or type 2 diabetes, but establishing genetic diagnosis is important, as treatment differs from the common types of diabetes. HNF1A-MODY has not been investigated in Croatia before due to limited access to genetic testing. In this study we aimed to describe the characteristics of young adults diagnosed with diabetes before the age of 45 years, who have rare HNF1A allele variants, and estimate the prevalence of HNF1A-MODY in Croatia. MATERIALS AND METHODS: We recruited 477 C-peptide positive and beta cell antibody negative subjects through the Croatian Diabetes Registry. HNF1A was sequenced for all participants and systematic assessment of the variants found was performed. The prevalence of HNF1A-MODY was calculated in the study group and results extrapolated to estimate the proportion of diabetic individuals with HNF1A-MODY in Croatia and the population prevalence. RESULTS: Our study identified 13 individuals harbouring rare HNF1A allelic variants. After systematic assessment, 8 were assigned a diagnosis of HNF1A-MODY. Two individuals were able to discontinue insulin treatment following the diagnosis. We estimated that HNF1A-MODY in Croatia has a prevalence of 66 (95% CI 61 - 72) cases per million. CONCLUSIONS: The estimated prevalence of HNF1A-MODY in Croatia is similar to that reported in other European countries. Finding cases lead to important treatment changes for patients. This strongly supports the introduction of diagnostic genetic testing for monogenic diabetes in Croatia.