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Metallothioneins (MTs) have been disclosed as a useful diagnostic factor for tumour progression and drug resistance in a variety of malignancies. Increased levels of MT in blood serum have been found in patients with several types of cancer, but there is no available information on serum MT levels in patients with testicular germ cell tumour (TGCT). The aim of the study was to determine MT levels in serum of patients with TGCT and to evaluate the portion of platinum (Pt) that binds to MT after cisplatin administration since MTs could be involved in drug resistance. Methods: Concentration of total MT was determined in serum of 25 men with newly diagnosed TGCT by differential pulse voltammetry. The fractionation of serum was carried out by size exclusion high-performance liquid chromatography (SE-HPLC), while concentration of Pt in collected fractions was determined by inductively coupled plasma mass spectrometry. Results: Concentration of serum MT was significantly higher in TGCT patients than in healthy volunteers. The results of SE- HPLC analysis showed that only a small amount of Pt was bound to proteins in the area of MT elution. Conclusions: Significant increase in MT levels in individuals with TGCT indicates certain health problem and, in combination with other commonly used diagnostic tools, could improve early diagnosis.

IMPORTANCE Approximately 50% of the risk for the development of testicular germ cell tumors (TGCTs) is estimated to be heritable, but no mendelian TGCT predisposition genes have yet been identified. It is hypothesized that inherited pathogenic DNA repair gene (DRG) alterations may drive susceptibility to TGCTs. OBJECTIVE To systematically evaluate the enrichment of germline pathogenic variants in the mendelian cancer predisposition DRGs in patients with TGCTs vs healthy controls. DESIGN, SETTING, AND PARTICIPANTS A case-control enrichment analysis was performed from January 2016 to May 2018 to screen for 48 DRGs in 205 unselected men with TGCT and 27 173 ancestry-matched cancer-free individuals from the Exome Aggregation Consortium cohort in the discovery stage. Significant findings were selectively replicated in independent cohorts of 448 unselected men with TGCTs and 442 population-matched controls, as well as 231 high-risk men with TGCTs and 3090 ancestry- matched controls. Statistical analysis took place from January to May 2018. MAIN OUTCOMES AND MEASURES Gene-level enrichment analysis of germline pathogenic variants in individuals with TGCTs relative to cancer-free controls. RESULTS Among 205 unselected men with TGCTs (mean [SD] age, 33.04 [9.67] years), 22 pathogenic germline DRG variants, one-third of which were in CHEK2 (OMIM 604373), were identified in 20 men (9.8% ; 95% CI, 6.1%-14.7%). Unselected men with TGCTs were approximately 4 times more likely to carry germline loss-of-function CHEK2 variants compared with cancer-free individuals from the Exome Aggregation Consortium cohort (odds ratio [OR], 3.87 ; 95% CI, 1.65-8.86 ; nominal P = .006 ; q = 0.018). Similar enrichment was also seen in an independent cohort of 448 unselected Croatian men with TGCTs (mean [SD] age, 31.98 [8.11] years) vs 442 unselected Croatian men without TGCTs (at least 50 years of age at time of sample collection) (OR, >1.4 ; P = .03) and 231 high-risk men with TGCTs (mean [SD] age, 31.54 [9.24] years) vs 3090 men (all older than 50 years) from the Penn Medicine Biobank (OR, 6.30 ; 95% CI, 2.34- 17.31 ; P = .001). The low-penetrance CHEK2 variant (p.Ile157Thr) was found to be a Croatian founder TGCT risk variant (OR, 3.93 ; 95% CI, 1.53-9.95 ; P = .002). Individuals with the pathogenic CHEK2 loss-of-function variants developed TGCTs 6 years earlier than individuals with CHEK2 wild-type alleles (5.95 years ; 95% CI, 1.48-10.42 ; P = .009). CONCLUSIONS AND RELEVANCE This multicenter case-control analysis of men with or without TGCTs provides evidence for CHEK2 as a novel moderate-penetrance TGCT susceptibility gene, with potential clinical utility. In addition to highlighting DNA-repair deficiency as a potential mechanism driving TGCT susceptibility, this analysis also provides new avenues to explore management strategies and biological investigations for high-risk individuals.

Genome-wide association studies in patients with testicular germ-cell tumors (TGCT) from Great Britain and the United States have identified six susceptibility loci in or near biologically plausible candidate genes. However, these loci have not been replicated in an independent European sample. We performed a genetic replication study of previously identified TGCT susceptibility loci in a Croatian case-control sample and performed additional analyses as concerning histological subtypes or tumor staging. We analyzed six single-nucleotide polymorphisms [rs2900333 (ATF7IP), rs210138 (BAK1), rs755383 (DMRT1), rs995030 (KITLG), rs4624820 (SPRY4), and rs4635969 (TERT/CLPTM1L)], each representing one of the published susceptibility loci/genes. Five susceptibility loci were found to be also associated in the Croatian population with P- values between 2.1e-10 (rs995030 ; odds ratio [OR] 3.08) and 0.01739 (rs4635969 ; OR 1.37), which remained statistically significant after correction for multiple testing. Although rs2900333 near ATF7IP just showed borderline association with all-TGCT (OR 1.24, P = 0.062), it showed significant association with the more aggressive forms of the tumor (OR 1.51, P = 0.0067)-a clinically interesting finding, which however has to be replicated in an independent sample. Assessment of cumulative risks revealed that men with at least seven risk alleles have a more than 2.5-fold increased disease risk (OR = 2.73, 95% confidence interval = 1.98-3.79). In summary, we independently replicated the majority of TGCT susceptibility loci identified previously in a Croatian sample and suggested a possible role of genetic variation near ATF7IP in regulating disease progression.

Prostate adenocarcinoma is the second most common solid neoplasm in male population in Croatia. It rarely causes symptoms unless it is advanced. The finding of PSA rise is the most common reason for diagnostic workout. Treatment plan is based on TNM classification, Gleason score and PSA. Clinically localized disease is successfully treated by radical prostatectomy or radiotherapy with or without hormonal therapy. Locally advanced disease is treated with radiotherapy and hormonal therapy. Metastatic disease can be controlled for many years by androgen deprivation. For castration resistant disease appropriate treatment is chemotherapy or secondary hormonal therapy. The following paper presents the clinical guidelines in order to standardize procedures and criteria for the diagnosis, management, management, treatment and monitoring of patients with prostate cancer in the Republic of Croatia.

Urothelial cancer is the most common bladder cancer. Hematuria is the most common presenting symptom in patients with bladder cancer. The most common diagnostics of bladder cancer is performed by transurethral resection of bladder after which pathohistological diagnosis is set. It is necessary to determine whether the cancer penetrated in muscle layer (muscle-invasive cancer) or not (muscle-noninvasive cancer). Decision on therapeutic modality depends on the clinical stage of disease and on prognostic and risk factors. For muscle non-invasive bladder cancer transurethral resection is preferred with or without intravesical instillation of Bacillus Calmette-Guérin (BCG). For invasive cancer the method of choice is radical cystectomy. Radiotherapy is used in radical and palliative purposes. Metastatic disease is most frequently treated by chemotherapy metotrexate/vinblastine/doxorubicine/cisplatin (MVAC) or gemcitabine/cisplatin (GC). The purpose of this article is to present clinical recommendations to set standards of procedures and criteria in diagnostics, treatment and follow up of patients with bladder cancer in the Republic of Croatia.

We report a case of a testicular seminoma patient with relapse who was irradiated after acute cerebral infarction induced by cisplatin- based chemotherapy. Lymphocytic genome instability was studied using an alkaline comet assay, analysis of structural chromosome aberrations, and cytokinesis-block micronucleus assay in blood samples collected before and after PET CT scanning that preceded radiotherapy, as well as before the administration of the first and after the administration of the last fraction of 3D conformal radiation. A challenge test with hydrogen peroxide (H2O2) was performed on isolated peripheral blood lymphocytes in order to establish to what extent earlier therapies had modified the response of the patient’s DNA to external stimuli with a genotoxic chemical. Levels of primary DNA damage in lymphocytes increased after diagnostic exposure, lowered prior to administration of a conformal 3D radiotherapy, and were the highest at the end of radiotherapy. Ex vivo exposure to H2O2 caused additional lymphocyte DNA damage, which gradually increased 15 and 30 minutes after treatment. Diagnostic and therapeutic exposure to radiation caused measurable cytogenetic damage that was subjected to extensive repair. All of the obtained results point to increased genomic instability in the patient which should be taken into account in his future medical surveillance.

Testicular seminoma cancer incidence has significantly increased over the last few decades, and although it is successfully treated by radiotherapy, long-term health risks are still unclear. The aim of the study was to show long- term genome damage in patients with seminoma after radiotherapy. Chromosome aberration (CA) and micronucleus (MN) assays seven years after radiotherapy with a total dose of 25 Gy were conducted in 10 testicular seminoma patients aged 23–49 years and results were compared with 10 healthy control subjects matched for age and smoking status. Although mean CA frequency did not deviate from control values, significantly increased frequencies of dicentrics, double minutes, and ring chromosomes were detected in seminoma patients. MN frequency in binuclear lymphocytes of patients was similar to controls (4.60/1000 vs. 5.82/1000, respectively). Significantly higher MN frequency was detected in mononuclear lymphocytes of patients than in controls (2.55/1000 vs. 0.73/1000, respectively). Average percentage of centromere-positive MN was 62.6% in seminoma patients. This study shows the persistence of unstable CA in seminoma patients seven years after radiotherapy and the relevance of long-term follow up. MN frequency in mononuclear lymphocytes was shown to be relevant biomarker of long-term genome damage.

Tumori testisa najčešći su solidni tumori u muškaraca u dobi od 15. do 34. godine. Njihova je incidencija u svijetu podvostručena u posljednjih 40 godina. Tumori zametnih stanica obuhvaćaju 95% svih tumora testisa, a podijeljeni su u dva osnovna histološka tipa: seminomi i neseminomi. Osobito značenje daje im visok postotak izlječivosti i u diseminiranoj fazi bolesti. Ovom uspjehu najviše je pridonijela kemoterapija, ali i dalje je kirurgija neizostavni dio uspješnog liječenja. Kod znatnog dijela ovih bolesnika danas se nastoji odrediti terapijski minimum kojim se izbjegava niz nuspojava, a koji dovodi do jednakog uspjeha kao i donedavno agresivniji terapijski pristup. U tekstu koji slijedi iznesene su kliničke upute radi standardizacije dijagnostike, terapije i kontrole bolesnika s tumorima zametnih stanica testisa u Republici Hrvatskoj., Testicular tumors are the most common solid tumors in men between 15 and 34 years of age. The worldwide incidence of these tumors has doubled in the past 40 years. Germ cell tumors comprise 95% of malignant tumors arising in the testes and they are classified either as seminoma or nonseminoma. Testicular cancers have a high cure rates even in disseminated stage of the disease. The chemotherapy mostly contributed to these results but surgery is an inevitable part of successful treatment. In a significant number of these patients treatment algorithms with minimum side effects are designed with the intention to maintain same cure rates as previously used, more aggressive therapy. The following text presents the clinical guidelines in order to standardize the procedures and criteria for diagnosis, management, treatment and follow-up of patients with testicular cancer in Republic of Croatia.

Urotelni rak najčešći je rak mokraćnog mjehura. Hematurija je najčešći simptom pri prezentaciji bolesti. Dijagnoza raka mokraćnog mjehura postavlja se uglavnom transuretralnom resekcijom nakon čega slijedi patohistološka dijagnoza. Nužno je utvrditi je li rak zahvatio mišićni sloj (mišićnoinvazivni rak) ili nije (mišićnoneinvazivni rak). Odluka o terapijskome modalitetu ovisi o kliničkom stadiju bolesti, prognostičkim čimbenicima i čimbenicima rizika. Za mišićnoneinvazivni rak mokraćnog mjehura uglavnom se preferira transuretralna resekcija tumora mokraćnog mjehura s intravezikalnom instilacijom Calmette-Guérinova bacila (BCG) ili bez nje. Za invazivni je rak metoda izbora radikalna cistektomija. Radioterapija se rabi u radikalne i palijativne svrhe. Metastatska bolest najčešće se liječi kemoterapijom metotreksat/vinblastin/doksorubicin/cisplatinom (MVAC) ili gemcitabin/cisplatinom (GC). Svrha je ovog članka predstavljanje kliničkih uputa s ciljem standardizacije postupaka i kriterija postavljanja dijagnoze, liječenja te praćenja bolesnika s rakom mokraćnog mjehura u Republici Hrvatskoj., Urothelial cancer is the most common bladder cancer. Hematuria is the most common presenting symptom in patients with bladder cancer. The most common diagnostics of bladder cancer is performed by transurethral resection of bladder after which pathohistological diagnosis is set. It is necessary to determine whether the cancer penetrated in muscle layer (muscle-invasive cancer) or not (muscle-noninvasive cancer). Decision on therapeutic modality depends on the clinical stage of disease and on prognostic and risk factors. For muscle non-invasive bladder cancer transurethral resection is preferred with or without intravesical instillation of Bacillus Calmette-Guérin (BCG). For invasive cancer the method of choice is radical cystectomy. Radiotherapy is used in radical and palliative purposes. Metastatic disease is most frequently treated by chemotherapy metotrexate/vinblastine/doxorubicine/cisplatin (MVAC) or gemcitabine/cisplatin (GC). The purpose of this article is to present clinical recommendations to set standards of procedures and criteria in diagnostics, treatment and follow up of patients with bladder cancer in the Republic of Croatia.

Adenokarcinom prostate druga je po učestalosti zloćudna neoplazija u muškaraca u Republici Hrvatskoj. Klinički je često asimptomatski, a najčešće se otkriva na osnovi povišenih vrijednosti PSA u serumu. Odluka o liječenju donosi se na osnovi TNM-klasifikacije, Gleasonova gradusa (stupnja diferenciranosti) i vrijednosti PSA. Klinički lokalizirana bolest liječi se vrlo uspješno radikalnom prostatektomijom ili radikalnom radioterapijom s hormonskom terapijom ili bez nje. Klinički lokalno uznapredovala bolest najčešće se liječi združenom primjenom radikalne radioterapije i hormonske terapije. Metastatska bolest može se godinama kontrolirati androgenom deprivacijom, a nakon razvoja bolesti rezistentne na kastraciju opravdana je kemoterapija ili dodatni oblici hormonske terapije. U tekstu koji slijedi predstavljene su kliničke upute s ciljem standardizacije postupaka i kriterija postavljanja dijagnoze, liječenja te praćenja bolesnika s rakom prostate u Republici Hrvatskoj., Prostate adenocarcinoma is the second most common solid neoplasm in male population in Croatia. It rarely causes symptoms unless it is advanced. The finding of PSA rise is the most common reason for diagnostic workout. Treatment plan is based on TNM classification, Gleason score and PSA. Clinically localized disease is successfully treated by radical prostatectomy or radiotherapy with or without hormonal therapy. Locally advanced disease is treated with radiotherapy and hormonal therapy. Metastatic disease can be controlled for many years by androgen deprivation. For castration resistant disease appropriate treatment is chemotherapy or secondary hormonal therapy. The following paper presents the clinical guidelines in order to standardize procedures and criteria for the diagnosis, management, management, treatment and monitoring of patients with prostate cancer in the Republic of Croatia.

Mammography as an x-ray method usually gives good results for lower density breasts while higher breast tissue densities significantly reduce the overall detection sensitivity and can lead to false negative results. In automatic detection algorithms knowledge about breast density can be useful for setting an appropriate decision threshold in order to produce more accurate detection. Because the overall intensity of mammograms is not directly correlated with the breast density we have decided to observe breast density as a texture classification problem. In this paper we propose breast density classification using feature selection process for different classifiers based on grayscale features of first and second order. In feature selection process different selection methods were used and obtained results show the improvement on overall classification by choosing the appropriate method and classifier. The classification accuracy has been tested on the mini-MIAS database and KBD-FER digital mammography database with different number of categories for each database. Obtained accuracy stretches between 97.2 % and 76.4 % for different number of categories., Mamografija je rendgenska metoda koja daje dobre rezultate pri slikanju dojki koje imaju manju gustoću, dok joj osjetljivost značajno opada pri snimanju dojki veće gustoće i time može doći do lažno pozitivnih rezultata. Poznavanje gustoće dojke može biti korisno kod algoritama za automatsku detekciju zbog mogućnosti određivanja praga odluke na osnovi tog znanja. S obzirom na to da ukupni intenzitet pojedinog mamograma nije izravno povezan s gustoćom, odlučili smo se promatrati gustoću kao problem klasifikacije teksture. U ovom radu predlažemo klasifikaciju dojki prema gustoći izborom izdvojenih značajki intenziteta prvog i drugog reda za različite klasifikatore. Za određivanje prikladnih značajki koristili smo različite metode i tako dobivene značajke pokazale su bolju točnost klasifikacije za odabrane klasifikatore. Točnost klasifikacije testirali smo na bazi mamografskih slika mini-MIAS i bazi digitalnih mamografskih slika KBD-FER s različitim brojem kategorija u koje su slike bile podijeljene. Postignuta točnost klasifikacije proteže se između 97,2 % i 76,4 % za različit broj kategorija u koje su mamogrami podijeljeni.

Side Effects of Adjuvant Radiotherapy in Men with Testicular Seminoma Stage IIn this study we followed up the side effects of adjuvant radiotherapy in patients with testicular seminoma stage I over a period from 13 to 84 months (median 28 months). The most frequent side effects during radiotherapy were gastrointestinal (nausea/vomiting), psychological, cognitive, and minor sexual problems.The reported side effects were treated by antiemetics and anxiolytics. After radiotherapy, the side effects persisted in 6 % of patients, but only a few of them required additional treatment. Healthy children were born to 76 % of patients in the 18 to 39 years age group. This study shows that adjuvant radiotherapy of the para-aortic lymph nodes with the total dosage of 24 Gy in 16 daily fractions administered to testicular seminoma patients causes acceptable side effects, does not adversely affect quality of life and fertility, if the approach to treatment is individual and family consulting is provided. This makes adjuvant radiotherapy of the para-aortic lymph nodes an acceptable treatment for testicular seminoma stage I patients.

Long-Term Follow-Up Study of Genome Damage Elimination in Patients with Testicular Seminoma Exposed to Ionising Radiation during RadiotherapyThe rate of genome damage elimination after therapeutic exposure to ionising radiation was estimated in stage I testicular seminoma patients monitored over a seven-year follow-up. DNA damage elimination in peripheral lymphocytes of ten subjects was analysed by the chromosome aberration assay. Seven years after the end of radiotherapy, significantly increased frequency of ring and dicentric chromosomes was still detected in comparison with baseline values. These results indicate the induction of genome instability. Long-term follow-up studies of cancer patients after radiotherapy could give us valuable information on the rate of genome damage elimination after exposure to ionising radiation and about the duration and manifestation of genome instability. This may be used in health risk assessment related to the possible development of secondary neoplasia. Studies such as this could have a great value both for oncology and radiation protection management protocols, especially after accidental overexposures.

The rate of genome damage elimination after therapeutic exposure to ionising radiation was estimated in stage I testicular seminoma patients monitored over a seven-year follow-up. DNA damage elimination in peripheral lymphocytes of ten subjects was analysed by the chromosome aberration assay. Seven years after the end of radiotherapy, signifi cantly increased frequency of ring and dicentric chromosomes was still detected in comparison with baseline values. These results indicate the induction of genome instability. Long-term follow-up studies of cancer patients after radiotherapy could give us valuable information on the rate of genome damage elimination after exposure to ionising radiation and about the duration and manifestation of genome instability. This may be used in health risk assessment related to the possible development of secondary neoplasia. Studies such as this could have a great value both for oncology and radiation protection management protocols, especially after accidental overexposures., U svrhu procjene uklanjanja oštećenja genoma nakon izlaganja ionizirajućem zračenju, sedam godina nakon radioterapije kod deset ispitanika sa seminomom testisa stadija I analizirana je učestalost strukturnih aberacija kromosoma u limfocitima periferne krvi. Sedam godina nakon radioterapije zabilježena je značajno povećana učestalost dicentričnih i prstenastih kromosoma u odnosu na kontrolne vrijednosti, što upućuje na moguću pojavu odgođene nestabilnosti genoma. Višegodišnje praćenje onkoloških pacijenata nakon radioterapije omogućuje skupljanje podataka o ritmu smanjenja oštećenja genoma i izazivanju genomske nestabilnosti (njezino trajanje i značajke) nužnih u procjeni zdravstvenog rizika, kao što su sekundarne neoplazije. Rezultati ove studije veoma su vrijedni za onkologiju i u izradi preventivnih mjera i propisa iz domene zaštite od ionizirajućeg zračenja u medicini te slučajevima nuklearnog akcidenta.

In this study we followed up the side effects of adjuvant radiotherapy in patients with testicular seminoma stage I over a period from 13 to 84 months (median 28 months). The most frequent side effects during radiotherapy were gastrointestinal (nausea/vomiting), psychological, cognitive, and minor sexual problems. The reported side effects were treated by antiemetics and anxiolytics. After radiotherapy, the side effects persisted in 6 % of patients, but only a few of them required additional treatment. Healthy children were born to 76 % of patients in the 18 to 39 years age group. This study shows that adjuvant radiotherapy of the para-aortic lymph nodes with the total dosage of 24 Gy in 16 daily fractions administered to testicular seminoma patients causes acceptable side effects, does not adversely affect quality of life and fertility, if the approach to treatment is individual and family consulting is provided. This makes adjuvant radiotherapy of the para-aortic lymph nodes an acceptable treatment for testicular seminoma stage I patients., su u periodu od 13 do 84 mjeseca (medijan 28 mjeseci). Tijekom radioterapije bolesnici su imali najčešće nuspojave od strane probavnog sustava (mučnina/povraćanje), psihološke i kognitivne probleme i blaže seksualne smetnje. Navedene nuspojave uspješno su tretirane antiemeticima i anksioliticima. Nakon radioterapije 76 % bolesnika dobne skupine od 18 do 39 godina ima zdravu djecu. Zaključno, ovo istraživanje pokazuje da adjuvantno zračenje paraaortalnih limfnih čvorova s ukupnom dozom od 24 Gy u 16 frakcija kod bolesnika sa seminomom testisa stadija I uzrokuje prihvatljive nuspojave uz prihvatljivu kvalitetu života, fertilitet, koristeći individualni pristup liječenju te obiteljsko savjetovalište. Adjuvantna radioterapija seminoma testisa stadija I je prihvatljiv oblik liječenja.

Background. Isolated ureteral metastasis from gastric cancer is extremely rare. Case report. We describe a 50 year old man with a history of subtotal gastrectomy who presented 4 years later with an ureteral metastasis. He was asymptomatic and diagnostic tests were performed due to the elevated creatinine level disclosed incidentally. The partial resection of distal right ureter as well as the resection of the right ureterovesical junction was performed with the implantation of double J stent. Histopathology revealed a metastasis of the adenocarcinoma that matched perfectly a tumour specimen from the gastric cancer surgery. It was first and isolated manifestation of gastric cancer dissemination. Conclusions. Although rare, the ureteral metastasis from gastric cancer can be the first, sole and asymptomatic manifestation of gastric cancer dissemination after a period of time.

The primary and residual genome damage and its elimination rate were evaluated in peripheral blood lymphocytes of breast cancer patients treated with adjuvant radiotherapy after surgical removal of the tumor by mastectomy or quadrantectomy. The levels of DNA/chromosome damage were estimated before, throughout, as well as after six months, respectively one year after the radiotherapy, using the alkaline comet assay, the chromosome aberration analysis and the cytokinesis-block micronucleus assay. The marked individual differences in the baseline genome damage were observed in patients, which additionally increased until the end of the radiotherapy cycle. The levels of DNA/cytogenetic damage slowly declined during post-irradiation period; although in the majority of subjects they did not return to pre-therapy levels. In addition to the well-established comet parameters, the long-tailed nuclei were also proved as a useful indicator of individual DNA damage and response to radiation. One of the most important observation was that older breast cancer patients, irradiated after mastectomy, had higher values of almost all parameters evaluated. We found positive correlations between the comet assay parameters and the cytogenetic biomarkers that confirmed their complementary value in the assessment of the radiation sensitivity/susceptibility in elderly breast cancer patients. The specific patterns of DNA damage observed in the majority of subjects after a prolonged exposure to ionizing radiation indicate the possibility of adaptive response. Such results may also be linked to the hormesis theory and support previous observations, but the underlying mechanisms should be further investigated on a much larger population.

Human testicular germ cell tumors (TGCTs) are histologically heterogenous neoplasms with a variable malignant potential. Two main groups of germ cell tumors occur in men: seminomas and nonseminomas. In the present study, a set of four tumor suppressor genes was investigated in testicular cancers. CDH1, APC, p53, and nm23-H1 genes were tested for loss of heterozygosity (LOH). Thirty-eight testicular germ cell tumors (17 seminomas and 21 nonseminomas) were analyzed by PCR using restriction fragment length polymorphism or the dinucleotide/tetranucleotide repeat polymorphism method. An allelic loss of p53 at exon 4 was detected in five nonseminomas, whereas LOH of p53 at intron 6 occurred in one of the seminoma and two of the nonseminoma samples. Allelic losses of the APC gene were present in three seminomas and one nonseminoma, whereas one seminoma and three nonseminomas showed LOH of CDH1. The analysis of allelic losses showed no common structural genetic alterations in tumor tissues, although a different pattern of LOH was observed between the two main histological groups of TGCTs. Copyright 2009 Elsevier GmbH. All rights reserved.

AIM: To estimate genome damage in oropharyngeal cancer patients before, during, and after radiotherapy and to measure the persistence of caused genome damage relevant in the evaluation of secondary cancer risk. METHODS: DNA damage was evaluated in peripheral blood lymphocytes of 10 oropharyngeal cancer patients using alkaline comet assay, analysis of structural chromosome aberrations, and micronucleus assay. Blood samples were taken 2 hours before irradiation on day 1 of the first radiotherapy cycle, 2 hours after the application of the first dose, in the middle of the radiotherapy cycle, within 2 hours after the last received radiotherapy dose, and after 6 and 12 months after radiotherapy. RESULTS: In most participants, the highest level of primary DNA damage was recorded in blood samples collected after the administration of first radiation dose (mean tail length 25.04+/-6.23 mum). Most patients also had increased frequency of comets with long tail-nucleus (LTN comets) after the administration of the first radiation dose (mean, 10.50+/-7.71 per 100 comets), which remained increased in the middle of radiotherapy (mean, 18.30+/-27.62 per 100 comets). Later on, the levels of primary DNA damage as recorded by the comet assay, slightly diminished. The frequency of structural chromosome aberrations in lymphocytes gradually increased during the radiation cycle (26.50+/-27.72 per 100 metaphases at the end of the therapy), as well as the frequency of micronuclei (mean total number of micronuclei 167.20+/-35.69 per 1000 binuclear cells). CONCLUSION: Oropharyngeal cancer patients had relatively high levels of primary DNA damage in their peripheral blood lymphocytes even before therapy. The frequency of complex structural chromosome aberrations and the frequency of micronuclei increased with the progression of the radiation cycle and the doses delivered. As the frequency of chromosomal aberrations a year after radiotherapy mostly did not return to pre-therapy values, it represents an important risk factor related to the onset of second cancer.

Background: Since testicular cancer shows different disease progress depending on etiology and the neoplastic tissue profile, with epigenetic changes being a likely underlying mechanism, we investigated CpG methylation of MGMT and RASSF1, which had been identified as promising candidate biomarkers for disease progression, chemotherapy success and prognosis. Methods: Genomic DNA was isolated from blood of 32 healthy individuals and 32 patients with testicular cancer before and after the chemotherapy: etoposide, cisplatin, bleomycin (BEP). Eighteen samples were seminomas and 14 were nonseminomas. For quantitative measurement of DNA methylation levels in MGMT and RASSF1A, bisulfite-converted DNA was amplified by PCR and then sequenced using a pyrosequencing technology. Results: Methylation levels were not significantly different for MGMT before and after chemotherapy ; however, methylation of the tested CpG sites in RASSF1 was significantly higher in patients before treatment compared with controls at 5 of 9 sites, two sites remaining significant even after the Bonferroni correction. Methylation of RASSF1 approached that of the controls after treatment. In addition, we found indications that additional stratification by histopathological profile might add value to MGMT and RASSF1 methylation as a prognostic marker. The methylation of LINE1 elements was similar in patients before and after chemotherapy. Conclusions: Increasing statistical power by studying larger cohorts has a potential to further confirm RASSF1 methylation as a chemotherapy success biomarker, while additional stratification by histopahological characteristics could give further insight leading to more accurate prognosis using both RASSF1 and MGMT, thereby enabling better risk- adapted management of testicular cancer.

U radu je prikazan pregled aktualnih globalnih navigacijskih sustava i elektroničkih navigacijskih sustava koji su im prethodili. Analizirani su sigurnosni zahtjevi u radu navigacijskih sustava, te su navedene prednosti i ograničenja pojedinoga navigacijskog sustava u odnosu prema ispunjavanju postavljenih zahtjeva., The paper has shown the review of current electronic global navigation systems as well as their predecessors. Safety requirements imposed on the operation of navigation systems have been analysed and the advantages and limits of specific navigation systems in relation to the fulfilment of the requirements imposed on them.

e15538 Background: Treatment of brain metastases (BM) in testicular germ cell tumors (TGCT) is still not fully resolved. There are conflicting data concerning the modalities of treatment in inopera...

e15509 Background: Despite the successfulness of testicular seminoma therapy experience in treatment of cases with disease relapse are of great interest. In the current study the results of treatment and patterns of relapse in seminoma stage I patients (pts) treated by adjuvant radiation therapy (RT) was evaluated. Methods: Study follows up 141 pts with stage I seminoma treated by adjuvant RT of paraaortic lymph nodes with a dose of 24 Gy in 16 fractions (fr) during the period of 8 years. Median ages at diagnosis were 35 years (19-72 y). The median follow-up period for pts treated with adjuvant RT was 6.5 years (range 3-10 y). Results: Of the total of 141 pts treated by RT, 6 pts (4%) experienced a relapse (5 in the pelvic lymph nodes, 1 in the mediastinal lymph nodes). Relapse occurred in the period of 3-21 months after RT. Three pts were treated with 4 cycles (cy) of BEP, one with a PE 4 cy, and one with relapse in the pelvis with 2 cy of BEP chemotherapy, later pelvic area was irradiated with a dose of 40Gy in 20 fr because he developed acute cerebral infarction. One patient with relapse in the pelvic lymph nodes measuring 4 cm refused chemotherapy and was treated to the pelvic area with a dose of 40Gy in 20 fr. Of the 6 pts who had a relapse, four had stage I B tumors, tumor sizes 4.5-8 cm, vascular and/or lymphatic invasion, 2 had positive rete testis (all had negative tumor markers). The 2 remaining pts had seminoma stage I A, one patient had tumor size of 6.5 cm (HCG 356 IU/L before orchiectomy), and the other patient had tumor size of 2 cm (LDH 669 U/L). Conclusions: All of 141 followed up pts are currently disease free. Disease relapse occurred in 4% of pts. The riskiest relapse time in our study is period 6-25 months after orchiectomy in pts who had (a) stage I B tumors and tumor size greater than 4 cm with vascular and/or lymphatic invasion (b) stage I A with elevated tumor markers LDH and bHCG before orchiectomy no matter on size of testicular tumors.

e15031 Background: Theetiology andreliable biomarkers for the risk of bilateral TGCT are still under investigation. Long-term relapse risks of up to 20 years after the therapy in contralateral testes demand a specific model of surveillance. Due to the rarity of the tumor type, reports of national experiences of bilateral TGCT are of a crucial significance for a future global database. Methods: The study was conducted during the treatment of 1 823 patients with TGCT in a single center from 1987-2011. Their mean age was 24 years at the time of diagnosis. Results: Out of 1 823 patients diagnosed with TGCT, 33 developed the bilateral disease (1.81%), 11 of them had synchronous tumors (33%). In the rest of patients the second testicular tumor was diagnosed 1 to 17 years after the initial diagnosis. The mean age of patients with bilateral TGCT was 28. According to the histological type: 11 were seminoma, 14 non-seminoma and 8 mixed seminoma and non-seminoma. Seven patients with bilateral tumor had a seminoma component at initial diagnosis. Compared to 5 patients out of 11 with synchronous tumor, the yolk sac component was detected only in 2 out of 22 metachronous patients. Conclusions: The presented findings of bilateral TGCT prevalence (1.8%) are in concordance with similar previous studies. As this type of tumor may be effectively treated, the risk assessment of metachronous tumor development should in future be facilitated by new biomarkers based on omics techniques. Thus, the investigation of karyotyping, c-KIT and transcriptome specificities will contribute to elucidation which pathways contribute to germ cell neoplasms. The stem cell markers for pluripotency maintenance may in future become potential diagnostic markers used as predictors for metastatic germ cell tumors. The development of a global database on these rare tumors will be of a crucial importance.

e15074 Background: Therapy options for patients (pts) with testicular seminoma stage I include radiotherapy (RT), chemotherapy or surveillance. Beside the therapy, acceptable side effects and life ...

e15075 Background: In addition to therapeutic efficiency and survival rate, the success of radiotherapy is also measured by side effects and long-term health risks. Secondary cancer incidence and i...

e15100 Background: Bleomycin, the main component of chemotherapy protocol for metastatic testicular germ-cell tumor (TGCT), may be inactivated by bleomycin hydrolase, encoded by BLMH1 gene. SNP A14...

e15147 Background: Although in some testicular cancer patients the elevated concentrations of the serum estradiol may be detected, the role of steroids in the etiology and progression of testicular...

21131 Background: The growing awareness of differences in inter-individual response to radiochemical exposure calls for a new approach in the therapy and follow-up of cancer patients. Results obtained by genotoxicological methods (Bonassi, 2006) showed that surrogate tissue could be used to predict cancer risk. Chromosome aberration (CA) and micronucleus (MN) assay enables:determination of radio- and chemosensitivity level in a patient, adjustment of therapy and detection of chromosomal rearrangements possibly related to the development of secondary cancer using fluorescent in situ hybridization (FISH) Methods: Ten women with breast cancer (BP) and 10 men with oropharinx cancer (OP) were analyzed before, during and after radiotherapy by CA and MN assay. Confounding parameters (age, diagnostics, smoking, drinking) were monitored and matched. Results were compared with 20 matched control subjects. The BP group received an irradiation dose of 60 Gy and the OP group of 62 Gy Results: Before therapy, the OP patients had a significantly higher MN frequency than BP and controls (23.2±4.9‰ versus 6.3±1.6 ‰ and 6.7±3.7‰). On measurements taken 6 and 12 months after the therapy, OP patients continued to have a significantly higher MN frequency than BP patients (60.2±11.4‰ vs. 8.4±2.4‰ and 30.7±4.7‰ vs.5.11±2.5‰, respectively). CA frequency was similar in both groups before therapy (2.5±1.1% in BC and 3.4±1.3% in OP; controls 1.2%). Twelve months after the therapy, the elimination of CA in OP patients was significantly slower than in BC patients (17.7±10.9% vs. 8±5.4%, respectively). As OP patients consumed more than 120 g/day of pure alcohol, it is possible that alcohol could have caused additional genome damage (Maffei, 2002). The highest inter-individual difference in genome damage was observed in BP patients Conclusions: The results show that the CA and MN assay are sensitive methods which can be used to introduce a new concept, oncogenotoxicology, whose goal is to improve the therapy results by evaluating inter-individual differences in response to radiochemical treatment and to improve the evaluation of risk of secondary cancer development. FISH in suspension (Wu, 2005) will allow automation of CA detection, and facilitate a more accurate prospective study of the same population. No significant financial relationships to disclose.

This paper presents an optimization of conformal antenna arrays - antennas which have the ability to mold to curved shaped surfaces. This surface has a spherical shape, and those elementary antennas could form two different arrays – two of several possible configurations has been chosen. Those known configurations of antenna arrays could be optimized in such a way to ensure better radiation pattern in comparison with the original element distribution. Radiation pattern was calculated using the method of moment and the spectral domain approach. Antenna arrays treated in such a way have the ability to produce the desired radiation pattern and they are capable of providing electronic scan coverage over the whole sphere and could also satisfy requirements for many applications.

Varicocele is dilatation of pampiniform venous plexus. It is associated with male infertility, as it is found in more than 40% of male partners in infertile couples. The main pathophysiological mechanism for impaired spermatogenesis is considered to be elevated scrotal temperature. Mainstay for diagnostic assessment of varicocele is physical examination and scrotal ultrasound/doppler. Thermography is a diagnostic method which measures temperature differences across the skin surface using a highly sensitive infrared camera. Currently there is no consensus regarding diagnostic parameters for thermography in diagnosis of varicocele. Aim of this study is to examine application of digital thermography in diagnosing varicocele. Material and methods: Study group consisted of 10 patients of mean age 18.2±2.4 (range=15.5-23.7). In all patients varicocele was detected incidentally on routine physical examination. All patients were evaluated by three methods. Infrared digital thermography was followed by physical examination and ultrasound/doppler. Infrared camera Thermo Tracer TH7102WL (NEC Sanei Instruments, Ltd., Japan) was used during all measurements. This infrared system has a geometric resolution of 76.800 pixels per picture (320x 240) and the minimum detectable temperature resolution (difference) is 0.07 °C at 30 °C (Normal mode). Results: Mean temperature at left pampiniforum plexus was 34.65±0.66 °C (range=34.1-36.3 °C) and at right pampiniform plexus 32.53±0.78 °C (range=31.5-33.5 °C). Temperature at left testicle was 33.58±0.97 °C (range=32.1-35 °C) while at right testicle it was 32.19±0.81 °C (range=31.2-33.5 °C). Temperature at pampiniform plexus higher than 34°C presents main thermographic sign of varicocele, while temperature at testicle higher than 32 °C is indicative of varicocele. Temperature difference between left and right pampiniform plexus was 2.12±1.08 °C (range=0.9-4.7 °C), and between testicles was 1.39±1.20 °C (range=0.1-3.6 °C). Thermography succesfully confirmed varicocele diagnosis in all patients. Conclusion: Digital infrared thermography presents feasible and low cost diagnostic method for varicocele. Further study on a larger number of patients and healthy participants is needed to evaluate sensitivity and specificity of this method and to establish consistent diagnostic parameters for thermographic assessment of varicocele.

Thermography is a biologically inert diagnostic method which measures temperature differences across the skin surface using a highly sensitive infrared camera. In oncology, application of this method is based on one of the biological characteristics of carcinogenesis - the rise in metabolic activity of proliferating tumor which is accompanied by an increase in surrounding temperature. We report 3 cases of diagnosed local recurrence using thermography surveillance, compared to magnetic resonance imaging (MRI) and pathohistlogical point to thermography that can provide additional promising tool to accepted surveillance procedures used in today's everyday clinic efforts.

There is a need for simple, noninvasive and reproducible test that could accurately reflect the inflammatory activity, and that could be used safely and repeatedly, during biological course of inflammatory bowel disease, such as ulcerative colitis. The aim of this study was to present the possibility of thermal imaging in assessing the inflammatory disease activity of ulcerative colitis. The authors presented the case of female patient with newly diagnosed, severe ulcerative pancolitis. The thermographic patterns, taken before starting the antiinflammatory treatment, and upon reaching the remission of the disease correlated with clinical and laboratory, and endoscopic findings, as well. This case report pointed out to diagnostic potential of infrared thermographs as a feasible and noninvasive method in evaluation of disease activity, in the patient with severe inflammatory bowel disease, such as acute pancolitis.

The pressure to improve software development process is not new, but in today’s competitive environment there is even greater emphasis on delivering a better service at lower cost. In market-driven development where time-to-market is of crucial importance, software development companies seek improvements that can decrease the lead-time and improve the delivery precision. One way to achieve this is by analyzing the test process since rework commonly accounts for more than half of the development time. A large reason for high rework costs is fault slippage from earlier phases where they are cheaper to find and remove. As an input to improvements, this article introduces a measure that can quantify this relationship. That is, a measure called faults-slip-through, which determines the faults that would have been more cost-effective to find in an earlier phase.

Cost efficiency and the issue of quality are pushing software companies to constantly invest in efforts to produce enough quality applications that will arrive in time, with good enough quality to the customer. Quality is not for free, it has a price. Using the different methods of prediction, characteristic parameters will be obtained and will lead to the conclusions about quality even prior the beginning of the project. The Weibull distribution is by far the world’s most popular statistical model for life data. On the other hand, exponential distribution and Rayleigh distribution are special cases of Weibull distribution. If we want to model and predict software component quality with mentioned distribution we should take some assumption regarding them. Prediction of component quality will take us to preventive and corrective action in the organization. Based on the results of prediction and modeling of software components faults prior the project start, during project execution and finally during maintenance stage of the component lifecycle some conclusion can be made. In this paper software component prediction using different mathematical models will be presented.

This paper presents effects that power consumption and a modulation technique used for data transmission have on the backscattered signal quality and output characteristics of tags rectifier circuit. Both higher power consumption and a higher duty cycle ratio (DCR) of the modulation used, degrade the performance of the passive backscatter based RFID tag. Measurements are conducted on the reader - tag system set to work on 13.56 MHz, with modulation frequencies of 10 kHz and 100 kHz, which corresponds to minimal bit rates of 10-kbps and 100-kbps, respectively.

An overview of a new Scalable Video Coding (SVC) extension of the H.264/AVC standard is given in this paper. A performance analysis is presented for quality and spatial scalability. Influence of the inter-layer prediction and the number of scalable layers to coding efficiency is shown. Results for CGS (coarse-grain quality scalability) and MGS (medium-grain quality scalability) coding are also compared.

Planning designing and efficient management of HIS require key technologies for successfull operation.