Interleukin-6 as a Predictive Factor of Pathological Response to FLOT Regimen Systemic Treatment in Locally Advanced Gastroesophageal Junction or Gastric Cancer Patients.

BACKGROUND: Perioperative treatment is a gold standard in locally advanced gastric cancer or GEJ cancer in the Western population. Unfortunately, the response rate after neoadjuvant chemotherapy (NAC) remains limited. Moreover, there are currently no biomarkers enabling an individual prediction of therapeutic efficacy. The aim of this study was the identification of serum biomarkers of early response to NAC. METHODS: We conducted this prospective study in the MSCNRIO in Warsaw, Poland. A total of 71 patients and 15 healthy volunteers gave informed consent. Complete blood count, carcinoembryonic antigen (CEA), carcinoma antigen 125 (CA125), carcinoma antigen 19.9 (CA19.9), and fibrinogen (F) were measured at baseline and before every cycle. Circulating tumour cells (CTCs) and interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10) were measured in a pilot group of 40 patients at baseline and before cycle two (C2) and cycle three (C3). RESULTS: Of all the measured parameters, only the IL-6 serum level was statistically significant. The IL-6 level before C2 of chemotherapy was significantly decreased in the complete pathological response (pCR) vs. the non-pCR group (3.71 pg/mL vs. 7.63 pg/mL, p = 0.004). In all patients with an IL-6 level below 5.0 pg/mL in C2, tumour regression TRG1a/1b according to the Becker classification and ypN0 were detected in postoperative histopathological specimens. The IL-6 level before C1 of chemotherapy was significantly elevated in ypN+ vs. ypN0 (7.69 pg/mL vs. 2.89 pg/mL, p = 0.022). CONCLUSIONS: The trial showed that an elevated level of IL-6 prior to treatment and C2 might be a predictor of pathological response to NAC.

Melanoma Mortality Trends in 28 European Countries: A Retrospective Analysis for the Years 1960-2020.

BACKGROUND: In 2020, in 27 European Union (EU) Member States, melanoma accounted for 4% of all new cancer cases and 1.3% of all cancer deaths, making melanoma the fifth most common malignancy and placing it in the 15 most frequent causes of cancer deaths in the EU-27. The main aim of our study was to investigate melanoma mortality trends in 25 EU Member States and three non-EU countries (Norway, Russia, and Switzerland) in a broad time perspective (1960-2020) in a younger (45-74 years old) vs. older age group (75+). METHODS: We identified melanoma deaths defined by ICD-10 codes C-43 for individuals aged 45-74 and 75+ years old between 1960-2020 in 25 EU Member States (excluding Iceland, Luxembourg, and Malta) and in 3 non-EU countries-Norway, Russia, and Switzerland. Age-standardized melanoma mortality rates (ASR) were computed using the direct age-standardization for Segi's World Standard Population. To determine melanoma-mortality trends with 95% confidence intervals (CI), Joinpoint regression was applied. Our analysis used the Join-point Regression Program, version 4.3.1.0 (National Cancer Institute, Bethesda, MD, USA). RESULTS: Regardless of the considered age groups, in all investigated countries, in general, melanoma standardized mortality rates were higher for men than women. Considering the age group 45-74, the highest number of countries was characterized by decreasing melanoma-mortality trends in both sexes-14 countries. Contrarily, the highest representation of countries in the age group 75+ was connected with increasing melanoma-mortality trends in both sexes-26 countries. Moreover, considering the older age group-75+-there was no country with a decreasing melanoma mortality in both sexes. CONCLUSIONS: Investigated melanoma-mortality trends vary in individual countries and age groups; however, a highly concerning phenomenon-increasing melanoma-mortality rates in both sexes-was observed in 7 countries for the younger age group and in as many as 26 countries for the older age group. There is a need for coordinated public-health actions to address this issue.

2022 revised European recommendations for the coding of the basis of diagnosis of cancer cases in population-based cancer registries.

The basis of diagnosis recommendations for population-based cancer registries aim to provide a standardized coding tool that reflects the certainty of cancer diagnosis, especially when pathological confirmation is lacking. The proportion of clinical diagnoses serves as an indicator of data quality. Given the evolving nature of diagnostic techniques, regular revision of the basis of diagnosis rules is crucial. To address this, a working group comprising representatives from the steering committee and member registries of the European Network of Cancer Registries was established. The original 1999 recommendations were comprehensively reviewed, resulting in the publication of an updated version. These new recommendations came into effect for incident cancer cases starting from January 1, 2023. The updated recommendations comprise an adapted code list for the basis of diagnosis, optional codes for histology cases, revisions related to flow cytometry, liquid biopsy, and cytogenetic/molecular testing, consolidation of histology codes 6 and 7, introduction of a new code 8 for cytogenetic/molecular confirmation, and establishment of new criteria for registering specific morphology codes in cancers lacking pathological confirmation.

Safety and efficacy of the FLOT regimen in the Polish population - an analysis of the prospective trial.

As gastric cancer is associated with poor prognosis, the preferred management of locally advanced gastric cancer (GC) and gastroesophageal junction (GEJ) cancer in European patients is perioperative chemotherapy using the FLOT regimen. Previously published data demonstrate that such treatment is associated with improved disease-free survival (DFS) as well as overall survival (OS) compared to ECF/ECX regimen. In order to collect biomaterial for the identification of serum biomarkers of an early response to neoadjuvant chemotherapy, we performed a prospective study and here, we report the safety and clinical efficacy of this prospective cohort. It was an academic, nonrandomized, prospective study, conducted at Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland. Between January 2018 and November 2019, we analyzed a total of 61 patients aged 30-77 (median 63 years, 52.5% males and 47.5% females) with histologically confirmed GC or GEJ cancer. The patients were qualified by a multidisciplinary team for perioperative treatment (FLOT regimen). All cases of reported adverse events were recorded and analyzed. All patients received G-CSF prophylactically. After gastrectomy, an assessment of pathological regression was performed according to the Becker classification. A total of 93.4% (57) patients completed four cycles of preoperative chemotherapy and 78.7% (48) received postoperative chemotherapy. All of them experienced grade 1/2 toxicities. The common AE G1/G2 in preoperative versus postoperative chemotherapy were: fatigue (75% vs. 60%), anemia (64% vs. 62%), nausea (60% vs. 60%), peripheral neuropathy (60% vs. 60%), and oral mucositis (59% vs. 50%), respectively. Only 24.6% (15) had G3/4 adverse events during preoperative chemotherapy and only 20.8% (10) during postoperative chemotherapy. The estimated DFS at 3 years was 53% (95% CI 40.5-66.1%) and the estimated OS at 3 years was 60.2% (95% CI 45.1-72.3%). FLOT regimen significantly improved GC and GEJ cancer patients' prognosis with acceptable side-effect profiles.

Breast cancer mortality trends in Europe among women in perimenopausal and postmenopausal age (45+).

INTRODUCTION: The aim of the study was to analyze breast cancer (BC) mortality trends among women at the age of 45 years old and older (45+) in the 28 European Union (EU) countries, as well as in 3 non-EU countries - Norway, Switzerland and the Russian Federation (control group) within the period 1959-2017. MATERIAL AND METHODS: Mortality and population data were sourced from the World Health Organization (WHO) database, and age-standardized mortality rates were calculated using the standard world population. Changes in mortality trends were analyzed using Joinpoint Trend Analysis Software. RESULTS: The majority of analyzed countries showed a meaningful decrease in BC mortality among women aged 45+. However, the results of our study suggest that there are 4 EU countries - Croatia, Poland, Romania and Slovakia - where increasing BC mortality trends started to be visible in the analyzed age group. Currently, the observed increase is still not significant, but the obtained data suggest the possibility of further continuation of the observed trend in the future. Moreover, in Bulgaria we also noted continuation of the increase in BC mortality (statistically significant). CONCLUSIONS: Due to the availability of better treatment options, as well as presence of effective tools for detecting BC at the early stages of progression, BC mortality is falling in most analyzed European countries. To maintain this situation and to stop BC mortality increase in the analyzed age group in Bulgaria, Croatia, Poland, Romania and Slovakia, immediate actions for improvement of BC management in the European health care systems should be considered.

A cross-sectional analysis of ex-smokers and characteristics associated with quitting smoking: The Polish Norwegian Study (PONS).

Tobacco smoking remains a number one preventable risk factor of premature death worldwide. Findings of recent research show concurrent trends of lung cancer deaths in males and females in Europe. Although lung cancer death rates are consistently decreasing in male population, in women an upward trend is observed. The burden of tobacco-related harm can be prevented by smoking cessation. The main goal of this analysis is to identify the crucial correlates of successful smoking cessation in the middle-aged Polish population. The data came from 13 172 survey participants south-eastern part of Poland as part of the PONS cohort study established in 2010. A total of 6998 records of those who were either ex-smokers or current smokers at baseline were analyzed. We applied logistic regression and adjusted for sociodemographic covariates and health determinants. Characteristics related to being an ex-smoker as opposed to a current smoker included: older age [men: odds ratio (OR)=1.03, 95% confidence interval (CI)=1.01-1.05; women: OR=1.05, 95% CI=1.03-1.07], being married or living together, having secondary (OR=1.51, 95% CI=1.14-1.99) or higher (OR=2.30, 95% CI=1.75-3.18) education (women), full-time employment (men), alcohol consumer (women), being overweight (men: OR=2.85, 95% CI=2.26-3.59; women: OR=1.60, 95% CI=1.36-1.87) or obese (men: OR=3.47, 95% CI=2.67-4.51; women: OR=2.99, 95% CI=2.45-3.65), having normal fasting glucose and cholesterol blood level without any treatment (women), assessing their own health highly (9-10, on the scale from 1 to 10) and having at least one accompanying chronic disease (women, OR=1.25, 95% CI=1.07-1.45). These findings provide valuable information on characteristics of ex-smokers as well as behavioral and sociodemographic predictors of successful cessation. Such data expand our knowledge and can be used to design a more comprehensive and targeted group-specific tobacco control policy focused on increasing the number of ex-smokers.

Comparison of E-cadherin with STAT3 and apoptosis regulators: Bak and Bcl-xL in endometrioid adenocarcinomas of different ER-alpha immunoprofile.

E-cadherin is a factor of good prognosis in endometrioid adenocarcinomas, while STAT3 is an oncogenic driver of carcinogenesis. E-cadherin, Bak, Bcl-xL and STAT3 were immunohistochemically detected in 78 human endometrioid adenocarcinomas. E-cadherin correlated with STAT3 (p <. 001, r = 0.537) as well as Bak (p = .005, r = 0.314) and Bcl-xL (p = .002, r = 0.340) in the whole study group. In G2 tumors, E-cadherin associated with Bak (p = .021, r = 0.319), Bcl-xL (p = .026, r = 0.309) and STAT3 (p <.001, r = 0.513) but not in G3 adenocarcinomas. E-cadherin correlated with Bak and Bcl-xL in both G1- and estrogen receptor (ER)-negative tumors with significant relation of E-cadherin and STAT3 in G1- and ER-negative tumors. Antigrowth synergy of expression was preserved for antiapoptotic Bak and proliferation-suppressing E-cadherin in IA adenocarcinomas (p = .031, r = 0.342) with no significance between Bak and E-cadherin or STAT3 and emerging correlation between E-cadherin and Bcl-xL in IB + II tumors instead (p = .003, r = 0.472). E-cadherin correlated with Bak and Bcl-xL in ER-positive adenocarcinomas (p = .002, r = 0.382 and p <.001, r = 0.439, respectively) but not in ER-negative tumors. In conclusion, expression deregulation of studied proteins is reflected in selective loss of correlation between suppressors of tumor growth (E-cadherin and Bak) presumably due to progressing impairment of growth-inhibitory properties of clone of neoplastic cells within higher staging and poorer differentiation.

Association of STAT3 with Cx26 and Cx43 in human uterine endometrioid adenocarcinoma.

Signal transducer and activator of transcription-3 (STAT3) drives endometrial carcinogenesis, while signaling via gap junctions gets weakened during cancer progression. Connexin 26 (Cx26), Cx43 and STAT3 were immunohistochemically evaluated in 78 endometrioid adenocarcinomas: Nuclear expression of STAT3 positively correlated with cytoplasmic immunoreactivity to Cx43 (P=0.004, r=0.318) and Cx26 (P=0.006, r=0.309). STAT3 correlated with Cx43 (P=0.022, r=0.411) and Cx26 (P=0.008 r=0.466) in G1 tumors. A statistically significant linkage remained in G2 cancers between STAT3 and Cx43 (P=0.061, r=0.262) and Cx26 (P=0.016, r=0.331); however, no correlations were observed in G3 tumors. STAT3 was significantly associated with Cx 43 (p=0.003, r=0.684) and Cx26 (p=0.049, r=0.500) in estrogen receptor (ER) negative adenocarcinomas. STAT3 did not correlate with Cx43 in ER positive adenocarcinomas; however, STAT3 expression remained correlated with Cx26 expression (P=0.035, r=0.268). In progesterone receptor negative tumors STAT3 was significantly associated with Cx43 (P=0.035, r=0.451) and Cx26 (P<0.0001, r=0.707). However, in PgR positive adenocarcinomas STAT3 correlated with Cx43 (P=0.03, r=0.290) but not with Cx26. Thus, it appears that hormone dependent acceleration of cancer growth breaks the association between STAT3 and Cx expression. These associations become weaker as the tumors dedifferentiate from G1 to G3 endometrioid adenocarcinomas. The present study provides evidence that the loss of correlation between STAT3 and selected Cx proteins occurs in tumors with more aggressive behavior.

Eventual proapoptotic or anti-apoptotic impact of aberrantly expressed Cx43 and Cx26 can depend on ER-alpha overexpression in human endometrioid adenocarcinoma.

Estrogen receptor (ER) and progesterone receptor (PgR) accumulations lead to impairment of gap junctional intercellular communication in endometrial cancer. The task of this study was to explore relationships of Cx26 and Cx43 with anti-apoptotic protein Bcl-xL and proapoptotic agent Bak in ER-alpha and PgR negative or variably positive endometrioid adenocarcinomas. Cx26, Cx43, Bak, Bcl-xL, PgR and ER-alpha were detected in 78 endometrioid adenocarcinomas with immunohistochemistry. There was a remarkable cellular re-distribution of Cx26 and Cx43 from normally membranous location in normal endometrium to aberrantly cytoplasmic expression in endometrioid adenocarcinomas, thus suggesting the decrease of functional membranous gap junctions in the malignancy. Bak failed to correlate with Cx43 regardless of either PgR or ER-alpha status of tumors, while Bcl-xL positively correlated with Cx43 in ER-alpha positive tumors (p = 0.001, r = 0.427) and both PgR positive (p = 0.019, r = 0.312) and negative (p = 0.015, r = 0.509) cancers. Similarly, Bcl-xL significantly associated with Cx26 in ER-alpha positive tumors (p = 0.036, r = 0.267) and both PgR positive (p = 0.026, r = 0.297) and negative (p = 0.046, r = 0.429) cancers. On the contrary, Bak exclusively correlated with Cx26 only in ER-alpha negative tumors (p = 0.027, r = 0.551). ER-alpha status of endometrioid adenocarcinomas could restrict eventual proapoptotic or anti-apoptotic impact of aberrantly expressed Cx43 and Cx26 in these tumors.

Regional variation in mortality from ischaemic heart disease in Poland, 2006-2010.

BACKGROUND: Spatial differences in mortality in Poland are large and remain unexplained to a large extent. Ischaemic heart disease (IHD) is a good candidate for explaining regional inequalities in mortality in Poland due to the high level of mortality from this cause and the large spatial differences. AIM: We describe the contribution of IHD to all-cause mortality in Poland in 2006-2010 on a powiat (Polish district) level and explain the differences in mortality by selected socio-economic factors. METHODS: We use mortality data from the population registry at the NUTS-4 level for 2006-2010. We map age-standardised all-cause and IHD mortality rates. The contribution of IHD mortality to all-cause mortality was also assessed through variance decomposition. Correlation coefficients between age-standardised mortality rates and selected socio-economic variables were estimated for all powiats and for a group excluding large cities. RESULTS: We demonstrated that regional differences between powiats in IHD mortality do not constitute a major factor behind regional mortality disparities in Poland. However, the spatial patterns for all-cause and IHD mortality in Polish powiats were both related to the level of urbanisation, with group of powiats characterised by the lowest IHD mortality comprising only large cities. The negative effect of large cities on the level of all-cause and IHD mortality was confirmed by the significant correlation between the socio-economic contextual variables, standing for the level of urbanisation, and IHD mortality. CONCLUSIONS: Ease of access to medical care in large cities and in particular to cardiology units is an important factor behind the levels of all-cause and IHD mortality in Poland.

Comparison of primarily diet-modifiable intestinal factors, connexin 43 and E-cadherin with TP53 and TGFB1 in colorectal cancer.

BACKGROUND/AIMS: Primarily, a diet (particularly dietary lipids and vitamins) can reversibly modify intestinal expressions of a few factors like connexin 43 (Cx43), E-cadherin (Cdh1), TP53 and TGFB1 with a special impact on immunity and mutagenesis. Malignant phenotype constitutes a diet-resistant signal streaming with engagement of these molecules which are generated in autonomous ways in colorectal cancer. METHODOLOGY: We aimed to compare adhesion proteins: (Cx43) and Cdh1 with TP53 and TGFB1 in colorectal adenocarcinomas. GJA1P1 and Cdh1 with TP53 and TGFB1 were detected with immunohistochemistry in the study of 106 colorectal adenocarcinomas. RESULTS: There was aberrant cytoplasmic expression instead of membranous one of Cx43 and Cdh1 reflecting constitutive destruction of intercellular ties while TP53 showed nuclear expression and TGFB1 accumulated in the cytoplasm. TP53 did not correlate with Cx43 (r=0.083, p=0.397) but correlated with Cdh1 (r=0.199, p=0.041). Cdh1 associated with TGFB1 reaching almost statistical significance (r=0.188, p=0.054), while TGFB1 correlated with Cx43 (r=0.359, p=0.001). CONCLUSIONS: The consequent and constant impairment of cancer intercellular communication seems to engage correlated with each other expressions of Cx43 and TGFB1 in colorectal cancer cells.

The relationships between hypoxia-dependent markers: HIF-1alpha, EPO and EPOR in colorectal cancer.

Hypoxia triggers production of several cytoprotective proteins. Hypoxia-inducible factor 1alpha (HIF-1α) is a powerful stimulator of transcription of many genes, including erythropoietin (EPO) in hypoxia-affected cells. Recent data have also implicated signaling by EPO receptor (EPOR) as a new factor influencing tumor progression. The aim of the study was to detect by immunohistochemistry the presence of HIF-1α, EPO and EPOR in colorectal cancer (CRC) in reference to clinicopathological variables. We found the presence of the studied proteins in specimens of all 125 CRC patients which is suggestive of the occurrence of hypoxia in colorectal cancer tissues. The expression of HIF-1α correlated significantly with the presence of EPO and EPOR in all samples (P < 0.001, r = 0.549 and P < 0.001, r = 0.536, respectively). Significant correlations (from P < 0.024 to P < 0.001) were found in the analyses of CRC subgroups such as histopathological type tumor, tumor grade, tumor stage and patients with lymph nodes metastases. The same high significant correlations (P < 0.001) were observed in group of sex, age and tumor location. However, the values of the correlation coefficients (r) which usually ranged from 0.5 to 0.6 suggest the existence of independent or concurrent mechanism stimulating generation of these proteins in colorectal cancer.

Role of immunohistochemical and histochemical profiling in H&E-based diagnosis of scrotal leiomyosarcoma of dartos muscle.

Histochemical and immunohistochemical methods should often but not always complement standardized histopathologic procedures. Here, we illustrate use of these ancillary techniques in a report of scrotal leiomyosarcoma. 62-year-old male patient presented with a palpable, subcutaneous 2,5 cm wide tumor arising from dartos muscle. The tumor was diagnosed leiomyosarcoma G2 pT1b. Interestingly, the sarcomatous mass was focally strictly attached to convoluted, benign bundles of smooth muscles that were intermingled with tumor mass at peripheral, lateral and superior sides of the lesion. We have used immune- and histochemical methods to confirm histopathological findings based on H&E staining. As expected, in tumor cells smooth muscle actin and desmin were strongly immunopositive similarly as Masson trichrome staining, while S100 and CD34 antigens were immunonegative except for sustained positivity for CD34 in vessels. The auxiliary staining methods can provide additional information on the tumorigenesis of leiomyosarcoma. They can also serve to determine additional features of prognostic significance, since e.g. immunoreactivity of CD34 accurately maps vascular density of tumor and enables a careful assessment of vascular invasion in course of leiomyosarcoma as well.

Tobacco smoking in countries of the European Union.

BACKGROUND: Existing smoking prevalence comparisons between the 'old' and 'new' members of the European Union (EU) give a misleading picture because of differences in methodology. A major EU project designed to find ways of closing the health gap between the member states, included the first ever comparison of smoking prevalence between these countries using a methodology that minimises potential biases. METHODS: A detailed analysis of methods and data from the most recent nationwide studies was conducted in the adult population of 27 countries of the European Union and Russia as an external comparator. To maximise comparability, daily smoking in the age range 20-64 was used. Prevalence of current daily smoking, former smoking and never smoking were age-standardised and calculated separately for males and females. FINDINGS: The European map of smoking prevalence shows that male smoking prevalence is much higher in the new than the old members of the EU, whereas in females the reverse is true, but there are also very large differences in smoking rates between particular countries within the same region. Sweden clearly has the lowest prevalence, and the prevalence in the United Kingdom (UK) at the time of the surveys emerges as near the average for old-Europe but higher than, for example, Ireland. INTERPRETATION: Restricting the analysis to daily smokers aged 20-64 produces a map of Europe in which variation in prevalence between individual countries within regions is as important as variation across regions. Survey methods need to be harmonised across countries to enable comparisons involving all ages and non-daily as well as daily smokers.

[Gap junction intercellular communication in carcinogenesis of endometrial cancer]. / Komunikacja miedzykomórkowa z udzialem polaczen typu gap w karcinogenezie blony sluzowej trzonu macicy.

One of the mechanisms for direct cell to cell signaling is mediated by gap junctions. These junctions are formed by connexins, transmembrane proteins. Gap junction intercellular communication (GJIC) plays a critical role in tissue development, differentiation of cells, and regulation of tissue homeostasis. Cancer cells are characterized by growth and/or differentiation disorders. Endometrial cancer is the most common gynecological malignancy in developed countries. In this study we discuss the putative role of GJIC and adhesion molecules in the development of endometrial cancer The relationships of GJIC to the process of apoptosis and function of some adhesion proteins have also been underlined.

STAT3 and apoptosis regulators: Bak and Bcl-xL in endometrioid adenocarcinomas of different estrogen receptor-α immunoprofile.

Estrogen receptor (ER) is a major feature of endometrioid adenocarcinoma. It has a significant impact on constitution of estrogen-responsiveness of this endometrial malignancy, in which STAT3 (signal transducer and activator of transcription) becomes hyperactivated. The aim of our study was to detect immunohistochemically and compare expressions of STAT3 with apoptosis regulators (Bak and Bcl-xL) in regard to different pathological features and variably pronounced ER-α immunoprofile in 78 endometrioid adenocarcinomas. STAT3 was abundantly detected in nuclei of cancer cells in 54 cases, thus pointing at its activation as an universal nuclear transcriptional factor. Bcl-xL and Bak were expressed in cytoplasm of malignant cells in 62 and 20 cancers, respectively. STAT3 correlated both with Bcl-xL (p = 0.001, r = 0.365) and Bak (p  < 0.001, r = 0.436) in all of endometrioid adenocarcinomas and variably in different subgroups of these tumours segregated in regard to grading, staging and patients' age. Remarkably, only ER-α positive cancers retained these correlations in opposition to ER-α negative tumours with negativity defined as an immunoreactivity below 10%. ER-α receptor probably enhances interactions between STAT3 and Bcl-xL to be present in statistically significant manner. Presence of ER-α receptor seems to be crucial for relationships among Bcl-xL and STAT3 to occur in endometrioid adenocarcinomas.

Prevalence of obesity - baseline assessment in the prospective cohort 'PONS' study.

OBJECTIVE: The aim of the study was to evaluate the prevalence of overweight and obesity in the population of Swietokrzyskie Province in Poland. METHODS: Body mass index (BMI), waist to hip ratio (WHR) and waist circumference (WC) in the Polish-Norwegian Study (PONS) was measured in 2,567 females and 1,287 males. Anthropometric measurements included fat mass, height, weight, waist and hip circumference. BMI and WHR were calculated. RESULTS: Data showed that 52% of males and 42% of females were overweight (25.0 ≤ BMI<30.0 kg/m2), and the prevalence of obesity (BMI ≥ 30.0 kg/m2) was 35% in both genders. The average BMI was higher in males (28.5 kg/m2) than in females (28.2 kg/m2). Analysis of WC showed that 36% of males and 45% of females had abdominal obesity, whereas measurements of WHR showed abdominal obesity in 64% of males and 79% of females. Generally, the prevalence of obesity was higher in the older age group (55-64 years) and in rural inhabitants. The prevalence of overweight increased with educational level, but the prevalence of obesity decreased with level of education in both males and females. CONCLUSIONS: Almost 80% of the PONS population were either overweight or obese; therefore, the PONS population is at increased risk of developing obesity-related diseases.

GLUT1 and Bcl-xL in relation to erythropoietin in human colorectal adenocarcinomas.

BACKGROUND/AIMS: GLUT1 and EPO belong to so called hypoxia-associated markers, which exert cytoprotective actions in the hypoxia suffering cells. In oxygen deficiency Bcl-xL can also be upregulated. METHODOLOGY: Therefore, we detected with immunohistochemistry and compared EPO with expressions of GLUT-1 and antiapoptotic protein Bcl-xL in 125 colorectal cancers. EPO correlated with GLUT-1 in all colorectal cancers (p < 0.001, r = 0.369). EPO expressions also associated with Bcl-xL (p < 0.001, r = 0.591) in all colorectal cancers. RESULTS: EPO correlated with GLUT-1 and Bcl-xL in subgroups of different nodal status, grading, staging, histopathological type, tumor site, patients' age and gender. However, the statistically significant relationship between EPO and GLUT-1 or Bcl-xL was lost in case of shallower neoplastic extent (pT1+pT2), but it was sustained in subgroup of deeper invading cancers (pT3+pT4) (p < 0.001, r = 0.355 and p < 0.001, r = 0.585, respectively). CONCLUSIONS: High expression of hypoxia dependent proteins (EPO, GLUT-1) indicates hypoxia of examined tissues of colorectal cancers. Cooperation may be reflected among the studied proteins by correlations between hypoxia dependent proteins (EPO vs. GLUT-1). Concerning functional significance of these investigated factors, subsequent promotion of cell survival could be maintained thanks to mutual impact of EPO and Bcl-xL on cellular viability in hypoxic environment of colorectal cancer.

Liver cirrhosis mortality in Europe, with special attention to Central and Eastern Europe.

BACKGROUND AND AIMS: Over the last decades, Europe has experienced dramatic changes in the geographical variation of liver cirrhosis rates. We attempt to provide a comprehensive analysis of patterns and trends in liver cirrhosis mortality in European countries and regions. METHODS: Age-standardized (world standard) liver cirrhosis mortality rates per 100,000 person-years at ages 20-64 for 35 separate countries were computed using the World Health Organization Mortality Database. RESULTS: In the analyzed period (1959-2002), a very strong East-to-West gradient in mortality rates was observed. An increase of the burden of mortality due to liver cirrhosis appeared in Eastern Europe in two specific areas: South-eastern Europe and North-eastern Europe. In the first group of countries, liver cirrhosis mortality was 10-20 times higher than in most other European states, levels never before observed in Europe. In the countries of North-eastern Europe (former Soviet Union countries) liver cirrhosis mortality was characterized by dramatic changes (both positive and negative) in specific periods of time. CONCLUSIONS: Despite the fact that the etiology of liver cirrhosis is multifactorial, it seems that alcohol drinking is the factor that best explains the observed patterns in frequency of this disease in Europe. Alcohol control policies in Central and Eastern Europe could lead to an appreciable reduction of premature mortality from liver cirrhosis.