Predictors of oropharyngeal cancer survival in Europe.

OBJECTIVES: HPV16-positive oropharyngeal cancer (OPC) patients experience better outcomes compared to HPV16-negative patients. Currently, strategies for treatment de-escalation are based on HPV status, smoking history and disease stage. However, the appropriate cut-point for smoking and the role of other non-clinical factors in OPC survival remains uncertain. MATERIALS AND METHODS: We examined factors associated with OPC outcome in 321 patients recruited in a large European multi-center study. Seropositivity for HPV16 E6 was used as a marker of HPV16 positive cancer. Hazard ratios (HR) and confidence intervals (CI) were estimated using Cox proportional models adjusted for potential confounders. RESULTS: Overall 5-year survival following OPC diagnosis was 50%. HPV16-positive OPC cases were at significantly lower risk of death (aHR = 0.51, 95% CI: 0.32-0.80). A significant effect on OPC survival was apparent for female sex (aHR 0.50: 95% CI: 0.29-0.85) and being underweight at diagnosis (aHR: 2.41, 95% CI: 1.38-4.21). A 10 pack year smoking history was not associated with overall survival. Higher stage at diagnosis appeared as the only factor significantly associated with OPC recurrence (aHR: 4.88, 95% CI: 2.12-11.21). CONCLUSION: This study confirms that HPV16 status is an independent prognostic factor for OPC survival while female sex lowers risk of death and being underweight at diagnosis increases the risk of death. Smoking was not an independent predictor of OPC survival.

High prevalence of mutant KRAS in circulating exosome-derived DNA from early-stage pancreatic cancer patients.

Background: Exosomes arise from viable cancer cells and may reflect a different biology than circulating cell-free DNA (cfDNA) shed from dying tissues. We compare exosome-derived DNA (exoDNA) to cfDNA in liquid biopsies of patients with pancreatic ductal adenocarcinoma (PDAC). Patients and methods: Patient samples were obtained between 2003 and 2010, with clinically annotated follow up to 2015. Droplet digital PCR was performed on exoDNA and cfDNA for sensitive detection of KRAS mutants at codons 12/13. A cumulative series of 263 individuals were studied, including a discovery cohort of 142 individuals: 68 PDAC patients of all stages; 20 PDAC patients initially staged with localized disease, with blood drawn after resection for curative intent; and 54 age-matched healthy controls. A validation cohort of 121 individuals (39 cancer patients and 82 healthy controls) was studied to validate KRAS detection rates in early-stage PDAC patients. Primary outcome was circulating KRAS status as detected by droplet digital PCR. Secondary outcomes were disease-free and overall survival. Results: KRAS mutations in exoDNA, were identified in 7.4%, 66.7%, 80%, and 85% of age-matched controls, localized, locally advanced, and metastatic PDAC patients, respectively. Comparatively, mutant KRAS cfDNA was detected in 14.8%, 45.5%, 30.8%, and 57.9% of these individuals. Higher exoKRAS MAFs were associated with decreased disease-free survival in patients with localized disease. In the validation cohort, mutant KRAS exoDNA was detected in 43.6% of early-stage PDAC patients and 20% of healthy controls. Conclusions: Exosomes are a distinct source of tumor DNA that may be complementary to other liquid biopsy DNA sources. A higher percentage of patients with localized PDAC exhibited detectable KRAS mutations in exoDNA than previously reported for cfDNA. A substantial minority of healthy samples demonstrated mutant KRAS in circulation, dictating careful consideration and application of liquid biopsy findings, which may limit its utility as a broad cancer-screening method.

International cancer seminars: a focus on kidney cancer.

Recent years have seen important advances in our understanding of the etiology, biology and genetics of kidney cancer. To summarize important achievements and identify prominent research questions that remain, a workshop was organized by IARC and the US NCI. A series of 'difficult questions' were formulated, which should be given future priority in the areas of population, genomic and clinical research.

Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium.

BACKGROUND: Type 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time-risk relationship are unclear, and there is limited information on the role of antidiabetic medications. PATIENTS AND METHODS: We analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates. RESULTS: Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14-0.69, for ≥15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75-8.35, for <5 years), but not for longer duration of use (OR 0.95, 95% CI 0.53-1.70, for ≥15 years). CONCLUSION: This study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics. It also shows that a 30% excess risk persists for more than two decades after diabetes diagnosis, thus supporting a causal role of diabetes in pancreatic cancer. Oral antidiabetics may decrease the risk of pancreatic cancer, whereas insulin showed an inconsistent duration-risk relationship.

Indoor air pollution from solid fuels and risk of upper aerodigestive tract cancers in central and eastern Europe.

BACKGROUND: Indoor air pollution from solid fuels is a potentially important risk factor for cancer, yet data on cancers from organs other than the lung are scarce. We investigated if indoor air pollution from coal and wood are risk factors for additional cancers, particularly that of the upper aerodigestive tract (oral cavity, larynx, pharynx and esophagus) in the high-risk areas of central and eastern Europe. METHODS: We used data from multi-center hospital-based case-control study of 1065 histologically confirmed upper aerodigestive tract cancer cases and 1346 controls. Standardized questionnaires were used to collect information on residential fuel use for cooking and heating. Using unconditional logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) for upper aerodigestive tract cancer risk after adjusting for potential confounders. RESULTS: Lifelong wood use was associated with pharyngeal and esophageal (OR 4.05, 95% CI: 1.30-12.68 and OR 2.71, 95% CI: 1.21-6.10, respectively). We observed an exposure-response relationship between duration of wood use and risk of pharyngeal cancer among those who had never used coal (P(trend)=0.04), ruling out the possibility of residual confounding by coal. Similarly, we observed an increased risk of laryngeal cancers and head & neck cancers among those who always used coal, with a noted exposure-response relationship (P(trend)<0.01). CONCLUSIONS: Our results suggest a possible role of indoor air pollution from solid fuel use in head and neck carcinogenesis in the high risk area of central and eastern Europe.

Incidence and prevalence of psoriatic arthritis, ankylosing spondylitis, and reactive arthritis in the first descriptive population-based study in the Czech Republic.

OBJECTIVE: To estimate the annual incidence and prevalence of psoriatic arthritis (PsA), ankylosing spondylitis (AS), and reactive arthritis (ReA) in a sample of the Czech population. METHODS: The population-based study was conducted in two regions of the Czech Republic (with a total population of 186000 inhabitants) in 2002-2003. Incident cases were registered on condition of confirming a definite diagnosis according to existing classification criteria during the study period (1 March 2002 to 1 March 2003). Prevalence was studied on the basis of identification of established diagnoses (before 1 March 2002) from registers of living patients of participating rheumatologists and other specialists. The age-standardized estimates of incidence and prevalence were calculated using the European standard population. RESULTS: The total annual incidence of PsA in adults aged >or= 16 years was 3.6/100000 [95% confidence interval (CI) 1.4-7.6/100000] and the prevalence of PsA was 49.1/100000 (95% CI 39.5-60.4/100000). The annual incidence of AS in adults was 6.4/100000 (95% CI 3.3-11.3/100000) and the prevalence of AS was 94.2/100000 (95% CI 80.8-109.2/100 000). The annual incidence of ReA in adults was 9.3/100000 (95% CI 5.5-14.8/100000) and the prevalence of ReA was 91.3/100000 (95% CI 78.1-106.2/100000). CONCLUSION: The annual incidence and prevalence rates of PsA, AS, and ReA in the first population-based survey in the Czech Republic compared well with data reported from other countries.

Life course social mobility and risk of upper aerodigestive tract cancer in men.

The aim of this study was to explore associations between social mobility and tumours of the upper aero-digestive tract (UADT), focussing on life-course transitions in social prestige (SP) based on occupational history. 1,796 cases diagnosed between 1993 and 2005 in ten European countries were compared with 1585 controls. SP was classified by the Standard International Occupational Prestige Scale (SIOPS) based on job histories. SIOPS was categorised in high (H), medium (M) and low (L). Time weighted average achieved and transitions between SP with nine trajectories: H --> H, H --> M, H --> L, M --> H, M --> M, M --> L, L --> H, L --> M and L --> L were analysed. Odds ratios (ORs) and 95%-confidence intervals [95%-CIs] were estimated with logistic regression models including age, consumption of fruits/vegetables, study centre, smoking and alcohol consumption. The adjusted OR for the lowest versus the highest of three categories (time weighted average of SP) was 1.28 [1.04-1.56]. The distance of SP widened between cases and controls during working life. The downward trajectory H --> L gave an OR of 1.71 [0.75-3.87] as compared to H --> H. Subjects with M --> M and L --> L trajectories ORs were also elevated relative to subjects with H --> H trajectories. The association between SP and UADT is not fully explained by confounding factors. Downward social trajectory during the life course may be an independent risk factor for UADT cancers.

TP53, EGFR, and KRAS mutations in relation to VHL inactivation and lifestyle risk factors in renal-cell carcinoma from central and eastern Europe.

Renal-cell carcinomas (RCC) are frequent in central and eastern Europe and the reasons remain unclear. Molecular mechanisms, except for VHL, have not been much investigated. We analysed 361 RCCs (334 clear-cell carcinomas) from a multi-centre case-control study for mutations in TP53 (exons 5-9 in the whole series and exons 4 and 10 in a pilot subset of 60 tumours) and a pilot 50 tumours for mutations in EGFR (exons 18-21) or KRAS (codon 12) in relation to VHL status. TP53 mutations were detected in 4% of clear-cell cases, independently of VHL mutations. In non-clear-cell carcinomas, they were detected in 11% of VHL-wild-type tumours and in 0% of tumours with VHL functional mutations. No mutations were found in EGFR or KRAS. We conclude that mutations in TP53, KRAS, or EGFR are not major contributors to the RCC development even in the absence of VHL inactivation. The prevalence of TP53 mutations in relation to VHL status may differ between clear-cell and other renal carcinomas.

Vitamin d pathway genes, diet, and risk of renal cell carcinoma.

Mediated by binding to the high-affinity vitamin D receptor (VDR), vitamin D forms a heterodimer complex with the retinoid-X-receptor (RXR). Variation in both genes has been shown to modify renal cell carcinoma (RCC) risk. Therefore, we investigated whether VDR and RXRA polymorphisms modify associations between RCC risk and frequency of dietary intake of vitamin D and calcium rich foods, and occupational ultraviolet exposure among 777 RCC case and 1035 controls from Central and Eastern Europe. A positive association was observed in this population between increasing dietary intake frequency of yogurt, while an inverse association was observed with egg intake frequency. RXRA polymorphisms, located 3' of the coding sequence, modified associations between specific vitamin D rich foods and RCC risk, while RXRA polymorphisms, located in introns 1 and 4, modified associations with specific calcium rich foods. Results suggest that variants in the RXRA gene modified the associations observed between RCC risk and calcium and vitamin D intake.

Genotype and haplotype analysis of TP53 gene and the risk of pancreatic cancer: an association study in the Czech Republic.

Pancreatic carcinoma is the fourth leading cause of cancer-related deaths in the Czech Republic, with only a minimum of patients surviving 5 years. The aetiology and molecular pathogenesis are still weakly understood. TP53 has a fundamental role in cell cycle and apoptosis and is frequently mutated in solid tumours, including pancreatic cancer. Based on the assumption that genetic variation may affect susceptibility to cancer development, the role of TP53 polymorphisms in modulating the risk of pancreatic cancer may be of major importance. We investigated four selected polymorphisms in TP53 (rs17878362:A(1)>A(2), rs1042522:G>C, rs12947788:C>T and rs17884306:G>A) in association with pancreatic cancer risk in a case-control study, including 240 cases and controls (for a total of 1827 individuals) from the Czech Republic. Carriers of the variant C allele of rs1042522 polymorphism were at an increased risk of pancreatic cancer [odds ratio (OR) 1.73; 95% confidence interval (CI) 1.26-2.39; P = 0.001]. Haplotype analysis showed that in comparison with the most common haplotype (A(1)GCG), the A(2)CCG haplotype was associated with an increased risk (OR 1.39; 95% CI 1.02-1.88; P = 0.034) and the A(1)CCG with a reduced risk (OR 0.30; 95% CI 0.12-0.76; P = 0.011) for this cancer. These results reflect previous findings of a recent association study, where haplotypes constructed on the same TP53 variants were associated with colorectal cancer risk [Polakova et al. (2009) Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic. Hum. Mutat., 30, 661-668.]. Genetic variation in TP53 may contribute, alone or in concert with other risk factors, to modify the inherited susceptibility to pancreatic cancer, as well as to other gastrointestinal cancers.

CYP1B1 gene polymorphism modifies pancreatic cancer risk but not survival.

UNLABELLED: Pancreatic cancer represents one of the biggest problems of current oncology. The risk factors of pancreatic cancer development, as well as factors affecting survival are poorly understood. Since biotransformation enzymes modify detoxification of carcinogens, we supposed, that arelationship between their polymorphism and the risk of pancreatic cancer development and eventually its clinical outcome may exist.
Associations of so far not studied cytochrome P450 1B1 (CYP1B1) polymorphisms with pancreatic cancer risk were investigated by case-control study. Atotal of 754 participants were recruited during study period. All patients were followed to determine their treatment and overall survival.
Carriers of rare genotype Val/Val in codon 432 of CYP1B1 (rs1056836) were under significantly lower risk of pancreatic cancer than wild type carriers (p=0.035). Carriers of heterozygous genotype (p=0.033) and rare allele Val (p=0.015) were also under lower risk than wild type carriers. When histology-verified patients were analyzed separately, even more significant associations were found (p=0.016, p=0.009, p=0.003, respectively). On the contrary, CYP1B1 polymorphism in codon 453 (rs1800440) did not significantly associate with pancreatic cancer risk. Median survival of patients with rare homozygous genotype Val/Val in CYP1B1-codon 432 was longer but not significantly different from those with wild-type homozygotes. The same was true for CYP1B1-codon 453 wild-type homozygotes in comparison with Ser/Ser rare homozygotes.
CYP1B1 polymorphism in codon 432 seems to modify the risk of pancreatic cancer development and should be further studied. KEYWORDS: Pancreatic cancer, CYP1B1, polymorphism, risk, survival.

Socioeconomic factors associated with risk of upper aerodigestive tract cancer in Europe.

INTRODUCTION: In the European Union, there are 180,000 new cases of upper aerodigestive tract (UADT) cancer cases per year--more than half of whom will die of the disease. Socioeconomic inequalities in UADT cancer incidence are recognised across Europe. We aimed to assess the components of socioeconomic risk both independently and through their influence on the known behavioural risk factors of smoking, alcohol consumption and diet. PATIENTS AND METHODS: A multicentre case-control study with 2198 cases of UADT cancer and 2141 controls from hospital and population sources was undertaken involving 14 centres from 10 countries. Personal interviews collected information on demographics, lifetime occupation history, smoking, alcohol consumption and diet. Socioeconomic status was measured by education, occupational social class and unemployment. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using unconditional logistic regression. RESULTS: When controlling for age, sex and centre significantly increased risks for UADT cancer were observed for those with low versus high educational attainment OR=1.98 (95% CI 1.67, 2.36). Similarly, for occupational socioeconomic indicators--comparing the lowest versus highest International Socio-Economic Index (ISEI) quartile for the longest occupation gave OR=1.60 (1.28, 2.00); and for unemployment OR=1.64 (1.24, 2.17). Statistical significance remained for low education when adjusting for smoking, alcohol and diet behaviours OR=1.29 (1.06, 1.57) in the multivariate analysis. Inequalities were observed only among men but not among women and were greater among those in the British Isles and Eastern European countries than in Southern and Central/Northern European countries. Associations were broadly consistent for subsite and source of controls (hospital and community). CONCLUSION: Socioeconomic inequalities for UADT cancers are only observed among men and are not totally explained by smoking, alcohol drinking and diet.

The association between glutathione S-transferase gene polymorphisms and pancreatic cancer in a central European Slavonic population.

In the first case-control study on pancreatic cancer conducted on 253 cases and 403 controls in the Czech Republic we observed that the GSTP1-codon 105 Val variant allele and the GSTT1-null genotype were associated with an elevated risk for pancreatic cancer (OR = 1.38; 95%CI = 0.96-1.97 and OR = 1.56; 95%CI = 0.93-2.61, respectively). Combination of GSTT1-null and GSTP1-codon 105 Val variants further increased the risk for pancreatic cancer (OR = 2.50; 95%CI = 1.20-5.20). In conclusion, this study suggests population-specific associations of polymorphisms in key biotransformation genes with elevated risk for pancreatic cancer.

Tobacco smoking, body mass index, hypertension, and kidney cancer risk in central and eastern Europe.

In a case-control study of kidney cancer in four central European countries, with 1097 incident cases and 1476 controls, we found an increased risk for self-reported hypertension and for obesity. Additional unknown risk factors are likely to be responsible for the high rates of kidney cancer in this region.

Renal cell carcinoma, occupational pesticide exposure and modification by glutathione S-transferase polymorphisms.

This study investigated associations between occupational pesticide exposure and renal cell carcinoma (RCC) risk. To follow-up on a previous report by Buzio et al., we also considered whether this association could be modified by glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) genotypes. About 1097 RCC cases and 1476 controls from Central and Eastern Europe were interviewed to collect data on lifetime occupational histories. Occupational information for jobs held for at least 12 months duration was coded for pesticide exposures and assessed for frequency and intensity of exposure. GSTM1 and GSTT1 gene deletions were analyzed using TaqMan assays. A significant increase in RCC risk was observed among subjects ever exposed to pesticides [odds ratio (OR): 1.60; 95% confidence interval (CI): 1.00-2.55]. After stratification by genotypes, increased risk was observed among exposed subjects with at least one GSTM1 active allele (OR: 4.00; 95% CI: 1.55-10.33) but not among exposed subjects with two GSTM1 inactive alleles compared with unexposed subjects with two inactive alleles (P-interaction: 0.04). Risk was highest among exposed subjects with both GSTM1 and GSTT1 active genotypes (OR: 6.47; 95% CI: 1.82-23.00; P-interaction: 0.02) compared with unexposed subjects with at least one GSTM1 or T1 inactive genotype. In the largest RCC case-control study with genotype information conducted to date, we observed that risk associated with pesticide exposure was exclusive to individuals with active GSTM1/T1 genotypes. These findings further support the hypothesis that glutathione S-transferase polymorphisms can modify RCC risk associated with occupational pesticide exposure.

Dietary risk factors for squamous cell carcinoma of the upper aerodigestive tract in central and eastern Europe.

OBJECTIVE: The incidence of squamous cell carcinoma of upper aerodigestive tract (UADT: oral cavity, pharynx, larynx, and esophagus) has been increasing in central and eastern European countries. We investigated the relationship between diet and UADT cancers in these high risk areas. METHODS: We used data from hospital-based case-control study of 948 UADT cancer cases and 1,228 controls conducted in Romania, Hungary, Poland, Russia, Slovakia, and Czech Republic. Standardized questionnaire were used to collect information on 23 different food items, along with alcohol and tobacco consumptions. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the UADT cancers after adjusting for center, age, sex, tobacco & alcohol intake, and other food groups. RESULTS: Consumption of dairy product was negatively associated with selected UADT cancers: larynx (OR: 0.38, CI: 0.23-0.62) and esophagus (OR: 0.55, CI: 0.33-0.93). While consumption of yellow/orange vegetables were inversely associated with oral/pharyngeal and laryngeal cancer (OR: 0.53, CI: 0.35-0.81 and OR: 0.62, CI: 0.38-1.00, respectively), preserved vegetable was positively associated with oral/pharyngeal and laryngeal cancer risk (p (trend) < 0.01 for both). CONCLUSION: Specific dietary components may play a role in the development of UADT cancers in the high-risk region of central and eastern Europe.

Vitamin D receptor polymorphisms and renal cancer risk in Central and Eastern Europe.

Previous studies investigated the role of vitamin D intake and cancer risk. The kidney is a major organ for vitamin D metabolism, activity, and calcium homeostasis; therefore, it was hypothesized that dietary vitamin D intake and polymorphisms in the vitamin D receptor (VDR) gene may modify renal cell carcinoma (RCC) risk. Three common VDR gene polymorphisms (BsmI, FokI, TaqI) were evaluated among 925 RCC cases and 1192 controls enrolled in a hospital-based case-control study conducted in Central and Eastern Europe. Overall associations with RCC risk were not observed; however, subgroup analyses revealed associations after stratification by median age of diagnosis and family history of cancer. Among subjects over 60 yr, reduced risks were observed among carriers of the f alleles in the FokI single-nucleotide polymorphism (SNP) (odds ratio [OR] = 0.61 for Ff and OR = 0.74 for ff genotypes) compared to subjects with the FF genotype (P trend = 0.04; P interaction = 0.004). Subjects with the BB BsmI genotype and a positive family history of cancer had lower risk compared to subjects with the bb allele (OR = 0.60; 95% CI: 0.33-1.1; P trend = 0.05). Genotype associations with these subgroups were not modified when dietary sources of vitamin D or calcium were considered. Additional studies of genetic variation in the VDR gene are warranted.

[Radical resection in patients with pancreatic head carcinomas. A retrospective survival analysis in a group of 307 subjects]. / Radikální resekce u nemocných s karcinomem hlavy pankreatu. Retrospektivní analýza prezívání u souboru 307 nemocných.

INTRODUCTION: The Czech Republic has the world's highest rates of pancreatic carcinomas. The pancreatic carcinoma is the fourth commonest cause of deaths due to malignancies, in our republic. Resection procedure is currently the only current treatment method, which has a curative potential and significantly prolongs a patient's life. AIM: To assess morbidity, mortality and survival of patients following radical and paliative procedures in the pancreatic head carcinoma patients. METHODS AND PATIENT GROUP: Only patients, who, based on the preoperative staging, were expected to require the following procedures, were indicated for surgery: I radical resection, i.e. stage I, II patients, 2 - palliative resection - i.e. stage III or IV patients, where no angioinvasion was detected preoperatively. Patients with peroperative detection of angioinvasion into the portomesenteric venous drainage area who required partial vein resection, were also included in the above subgroup. 3 - palliative bypass, where longer survival was expected. Radical resection included proximal pancreatoduodenectomy (PDE) with preservation of the pylorus according to Traverso-Longmire, with N1-2 lymphadenectomy and with reconstruction to an excluded jejunal loop. The same procedure was followed in cases of palliative resections. The collected data were statistically assessed using the Logrank test. From 05/1998 to 12/2006, a total of 307 patients with carcinomas of the pancreas and the Vater papila were treated. In 242 patients, the carcinoma was located within the pancreatic head, in 65 subjects, the pancreatic body and cauda were affected. Resection for the pancreatic head carcinoma was performed in 78 patients: 46 males, 32 females, the mean age was 63.5 y.o.a, with the median of 64 years. Bypass procedures were performed in 109 subjects and explorations in 55 subjects. RESULTS: Surgical procedures, with exception of 55 subjects who underwent exploration only, were performed in 187 subjects. Out of the total 78 PDEs, resections in stage I and II were performed in 22 subjects, in stage III in 41 subjects. In the group of 63 radical resection subjects, 2 subjects exited: the first one due to multiorgan failure, the second one for necrotizing postoperative pancreatitis. In the group of 15 palliative resections, 3 subjects exited. 10 patients died during the early postoperative period after palliative bypass procedures. A total of 15 subjects, i.e. 8%, exited during the early postoperative period. 5 subjects exited after resection procedures, i.e. 6.4%, 3% after radical resections. 3 subjects exited after palliative resections. Early complications were recorded in 44 subjects: pancreato-jejuno anastomosis insufficiency in 6 patients, insufficiency of hepaticojejunoanastomosis in 5 subjects, postoperative pancreatitis in 5 subjects, intraabdominal absces in 10 subjects, wounds infections with secondary healing in 19 subjects and cardiopulmonary complications in 33 subjects. In 19 subjects (43% of all complications), surgical revision was performed. Three-year survival rates were recorded in 60, resp. 29.5 and 39.5% of the patients in stage I, resp. II and III, while they were recorded in 15.6.% of the stage IVa subjects and only in 10.5% of the stage IVb subjects. There is a significant difference between survival rates of the stage I, II and III patients, compared to the stage IV patients (p < 0.005). There is no significant difference in the over- 3-years survival rates between the patients undergoing radical or palliative resections, however, the radical resection patients have significantly higher survival rates 3 months to 2 years postoperatively (p < 0.05). The radical resection subjects have significantly higher survival rates during the first 36 postoperative months, compared to the palliative resection and BDA subjects (p < 0.05). Comparison of sur vival rates in patients with radical or palliative resections is affected by a small number of the palliative resection subjects (n = 15), where no differences in survival rates were detected from the end of 9th postoperative month to the end of 3rd postoperative year. There is a significant difference in the survival rates between the resection and exploration subjects (p < 0.05). The survival rates differences between the subjects with palliative resections and BDAs cannot be evaluated in our study, due to nonhomogenity of the subjects. CONCLUSION: Radical PDEs for the pancreatic head carcinoma results in significantly longer survival of the subjects, compared to palliative bypasses. Stage I, II or III patients survive significantly longer, compared to those operated in stage IV.

Glutathione S-transferase polymorphisms, cruciferous vegetable intake and cancer risk in the Central and Eastern European Kidney Cancer Study.

High consumption of cruciferous vegetables has been associated with reduced kidney cancer risk in many studies. Isothiocyanates, thought to be responsible for the chemopreventive properties of this food group, are conjugated to glutathione by glutathione S-transferases (GSTs) before urinary excretion. Modification of this relationship by host genetic factors is unknown. We investigated cruciferous vegetable intake in 1097 cases and 1555 controls enrolled in a multicentric case-control study from the Czech Republic, Poland, Romania and Russia. To assess possible gene-diet interactions, genotyped cases (N = 925) and controls (N = 1247) for selected functional or non-synonymous polymorphisms including the GSTM1 deletion, GSTM3 3 bp deletion (IVS6 + 22-AGG) and V224I G>A substitution, GSTT1 deletion and the GSTP1 I105V A>G substitution. The odds ratio (OR) for low (less than once per month) versus high (at least once per week) intake of cruciferous vegetables was 1.29 [95% confidence interval (CI): 1.02-1.62; P-trend = 0.03]. When low intake of cruciferous vegetables (less than once per month) was stratified by GST genotype, higher kidney cancer risks were observed among individuals with the GSTT1 null (OR = 1.86; 95% CI: 1.07-3.23; P-interaction = 0.05) or with both GSTM1/T1 null genotypes (OR = 2.49; 95% CI: 1.08-5.77; P-interaction = 0.05). These data provide additional evidence for the role of cruciferous vegetables in cancer prevention among individuals with common, functional genetic polymorphisms.

Epidemiology of rheumatoid arthritis, juvenile idiopathic arthritis and gout in two regions of the Czech Republic in a descriptive population-based survey in 2002-2003.

OBJECTIVE: To estimate the annual incidence and prevalence of rheumatoid arthritis (RA), juvenile arthritis (JIA) and gout in a population based study in two regions of the Czech Republic with total population of 186,000 inhabitants. METHODS: The study was conducted in the Town of Ceske Budejovice and district of Cheb in the Czech Republic (with a total population of 186,000 inhabitants) in the years 2002 and 2003. Incident cases were registered on condition that the definite diagnosis was confirmed according to existing classification criteria during the study period. Prevalence was studied on the basis of identification of established diagnosis from registers of patients of participating rheumatologists and other specialists. They were asked to report all living patients who had been diagnosed before 1st March 2002. Patients were only included in the study if their permanent address was in the selected study area. RESULTS: Overall, we found 48 incident and 947 prevalent cases of RA among adults (16+ years), 4 incident and 43 prevalent cases of JIA among children (less than 16 years old), and 64 incident and 425 prevalent cases of gout among adults (16+ years). The total annual incidence of RA was 31/100,000 in the adult population aged 16 years and more (95% CI 20 to 42/100,000). The prevalence of RA was 610/100,000 (95% CI 561 to 658/100,000) in the adult population. An annual incidence of gout in adults was 41/100,000 (95% CI 28 to 53/100,000). The prevalence of gout was 300/100,000 (95% CI 266 to 334/100,000). The annual incidence of JIA was 13/100,000 in children less than 16 years old (95%CI 1 to 20/100,000). The prevalence of JIA in children was 140/100,000 (95% CI 117 to 280/100,000). CONCLUSION: This study estimates the annual incidence and prevalence rates of RA, gout and JIA in the first population-based survey in the Czech Republic. The rates of RA and JIA compare well with figures reported from other countries; figures in gout seem to be lower than reported elsewhere.