INTRODUCTION: In developed countries, urologic fistulas arise mainly from malignancies, radiotherapy, or surgical trauma. Hysterectomy and radiation therapy are both critical components of the treatment of women with cancers. Urologic fistulas significantly reduce the quality of life of cancer patients, and may result in delays or even refusal of adjuvant treatment by these patients, thereby negatively impacting both short- and long-term cancer survival. MATERIALS AND METHODS: A 10-year retrospective study of urologic fistulas associated with gynaecologic malignancies at the University hospital Hradec Kralove, Czech Republic was conducted. Descriptive statistics of the fistula and treatment characteristics of women with malignant fistulas were conducted using the NCSS 22 statistical software program (NCSS, Keysville, Utah). RESULTS: Cervical cancer was mostly commonly associated with urologic fistulas (36, 76.8%). Most of the malignant fistulas were complex (41, 87.2%) vesicovaginal (23, 48.9%) fistulas (VVFs). More than two-thirds (33, 70.2%) of the fistulas were diagnosed following radiotherapy, with a time interval from radiotherapy to fistula diagnosis of between 3.00 and 14.50 years. Primary fistuloraphy was performed for all the six cases with simple VVFs and seven (41.2%) of the 17 patients with complex VVFs. Treatment success rate was 83.33% and 14.3% for simple and complex fistulas, respectively. All the failed complex fistula repairs recurred. CONCLUSION: Malignant fistulas predominantly follow radiotherapy for cervical cancers, and are usually detected up to 15 years post-radiotherapy. Most are complex VVFs, which are difficult to treat, with a high rate of recurrence.

• MeSH
• dospělí MeSH
• hysterektomie škodlivé účinky   MeSH
• kvalita života MeSH
• lidé středního věku MeSH
• lidé MeSH
• močové píštěle * etiologie   epidemiologie   MeSH
• nádory děložního čípku * komplikace   MeSH
• nádory ženských pohlavních orgánů * komplikace   terapie   patologie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• vezikovaginální píštěl * etiologie   epidemiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

As the great majority of gene expression (GE) biodosimetry studies have been performed using blood as the preferred source of tissue, searching for simple and less-invasive sampling methods is important when considering biodosimetry approaches. Knowing that whole saliva contains an ultrafiltrate of blood and white blood cells, it is expected that the findings in blood can also be found in saliva. This human in vivo study aims to examine radiation-induced GE changes in saliva for biodosimetry purposes and to predict radiation-induced disease, which is yet poorly characterized. Furthermore, we examined whether transcriptional biomarkers in blood can also be found equivalently in saliva. Saliva and blood samples were collected in parallel from radiotherapy (RT) treated patients who suffered from head and neck cancer (n = 8) undergoing fractioned partial-body irradiations (1.8 Gy/fraction and 50-70 Gy total dose). Samples were taken 12-24 h before first irradiation and ideally 24 and 48 h, as well as 5 weeks after radiotherapy onset. Due to the low quality and quantity of isolated RNA samples from one patient, they had to be excluded from further analysis, leaving a total of 24 saliva and 24 blood samples from 7 patients eligible for analysis. Using qRT-PCR, 18S rRNA and 16S rRNA (the ratio being a surrogate for the relative human RNA/bacterial burden), four housekeeping genes and nine mRNAs previously identified as radiation responsive in blood-based studies were detected. Significant GE associations with absorbed dose were found for five genes and after the 2nd radiotherapy fraction, shown by, e.g., the increase of CDKN1A (2.0 fold, P = 0.017) and FDXR (1.9 fold increased, P = 0.002). After the 25th radiotherapy fraction, however, all four genes (FDXR, DDB2, POU2AF1, WNT3) predicting ARS (acute radiation syndrome) severity, as well as further genes (including CCNG1 [median-fold change (FC) = 0.3, P = 0.013], and GADD45A (median-FC = 0.3, P = 0.031)) appeared significantly downregulated (FC = 0.3, P = 0.01-0.03). A significant association of CCNG1, POU2AF1, HPRT1, and WNT3 (P = 0.006-0.04) with acute or late radiotoxicity could be shown before the onset of these clinical outcomes. In an established set of four genes predicting acute health effects in blood, the response in saliva samples was similar to the expected up- (FDXR, DDB2) or downregulation (POU2AF1, WNT3) in blood for up to 71% of the measurements. Comparing GE responses (PHPT1, CCNG1, CDKN1A, GADD45A, SESN1) in saliva and blood samples, there was a significant linear association between saliva and blood response of CDKN1A (R2 = 0.60, P = 0.0004). However, the GE pattern of other genes differed between saliva and blood. In summary, the current human in vivo study, (I) reveals significant radiation-induced GE associations of five transcriptional biomarkers in salivary samples, (II) suggests genes predicting diverse clinical outcomes such as acute and late radiotoxicity as well as ARS severity, and (III) supports the view that blood-based GE response can be reflected in saliva samples, indicating that saliva is a "mirror of the body" for certain but not all genes and, thus, studies for each gene of interest in blood are required for saliva.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory hlavy a krku radioterapie   MeSH
• radiometrie MeSH
• senioři MeSH
• sliny * účinky záření   metabolismus   MeSH
• vztah dávky záření a odpovědi MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Isolation of RNA from whole saliva, a non-invasive and easily accessible biofluid that is an attractive alternative to blood for high-throughput biodosimetry of radiological/nuclear victims might be of clinical significance for prediction and diagnosis of disease. In a previous analysis of 12 human samples we identified two challenges to measuring gene expression from total RNA: (1) the fraction of human RNA in whole saliva was low and (2) the bacterial contamination was overwhelming. To overcome these challenges, we performed selective cDNA synthesis for human RNA species only by employing poly(A)+-tail primers followed by qRT-PCR. In the current study, this approach was independently validated on 91 samples from 61 healthy donors. Additionally, we used the ratio of human to bacterial RNA to adjust the input RNA to include equal amounts of human RNA across all samples before cDNA synthesis, which then ensured comparable analysis using the same base human input material. Furthermore, we examined relative levels of ten known housekeeping genes, and assessed inter- and intra-individual differences in 61 salivary RNA isolates, while considering effects of demographical factors (e.g. sex, age), epidemiological factors comprising social habits (e.g. alcohol, cigarette consumption), oral hygiene (e.g. flossing, mouthwash), previous radiological diagnostic procedures (e.g. number of CT-scans) and saliva collection time (circadian periodic). Total human RNA amounts appeared significantly associated with age only (P ≤ 0.02). None of the chosen housekeeping genes showed significant circadian periodicity and either did not associate or were weakly associated with the 24 confounders examined, with one exception, 60% of genes were altered by mouthwash. ATP6, ACTB and B2M represented genes with the highest mean baseline expression (Ct-values ≤ 30) and were detected in all samples. Combining these housekeeping genes for normalization purposes did not decrease inter-individual variance, but increased the robustness. In summary, our work addresses critical confounders and provides important information for the successful examination of gene expression in human whole saliva.

• MeSH
• bakteriální RNA MeSH
• dospělí MeSH
• esenciální geny * MeSH
• exprese genu * MeSH
• komplementární DNA MeSH
• kontaminace DNA MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• RNA izolace a purifikace   MeSH
• sliny metabolismus   MeSH
• stanovení celkové genové exprese metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• celotělové ozáření MeSH
• lidé MeSH
• Papio * MeSH
• radiobiologie MeSH
• regulace genové exprese účinky záření   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The research for high-throughput diagnostic tests for victims of radio/nuclear incidents remains ongoing. In this context, we have previously identified candidate genes that predict risk of late-occurring hematologic acute radiation syndrome (HARS) in a baboon model. The goal of the current study was to validate these genes after radiation exposure in humans. We also examined ex vivo relative to in vivo measurements in both species and describe dose-response relationships. Eighteen baboons were irradiated in vivo to simulate different patterns of partial- or total-body irradiation (TBI), corresponding to an equivalent dose of 2.5 or 5 Sv. Human in vivo blood samples were obtained from patients exposed to different dose ranges: diagnostic computerized tomography (CT; 0.004-0.018 Sv); radiotherapy for prostate cancer (0.25-0.3 Sv); and TBI of leukemia patients (2 × 1.5 or 2 × 2 Sv, five patients each). Peripheral whole blood of another five baboons and human samples from five healthy donors were cultivated ex vivo and irradiated with 0-4 Sv. RNA was isolated pairwise before and 24 h after irradiation and converted into cDNA. Gene expression of six promising candidate genes found previously by us in a baboon model ( WNT3, POU2AF1, CCR7, ARG2, CD177, WLS), as well as three genes commonly used in ex vivo whole blood experiments ( FDXR, PCNA, DDB2) was measured using qRT-PCR. We confirmed the six baboon candidate genes in leukemia patients. However, expression for the candidate gene FDXR showed an inverse relationship, as it was downregulated in baboons and upregulated in human samples. Comparisons among the in vivo and ex vivo experiments revealed the same pattern in both species and indicated peripheral blood cells to represent the radiation-responsive targets causing WNT3 and POU2AF1 gene expression changes. CCR7, ARG2, CD177 and WLS appeared to be altered due to radiation-responsive targets other than the whole blood cells. Linear dose-response relationships of FDXR, WNT3 and POU2AF1 using human ex vivo samples corresponded with human in vivo samples, suggesting that ex vivo models for in vivo dose estimates can be used over a wide dose range (0.001-5 Sv for POU2AF1). In summary, we validated six baboon candidate genes in humans, but the FDXR measurements underscored the importance of independent assessments even when candidates from animal models have striking gene sequence homology to humans. Since whole blood cells represented the same radiation-responsive targets for FDXR, WNT3 and POU2AF1 gene expression changes, ex vivo cell culture models can be utilized for in vivo dose estimates over a dose range covering up to 3.5 log scales. These findings might be a step forward in the development of a gene expression-based high-throughput diagnostic test for populations involved in large-scale radio/nuclear incidents.

• MeSH
• celotělové ozáření MeSH
• dospělí MeSH
• druhová specificita MeSH
• lidé středního věku MeSH
• lidé MeSH
• Papio * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transkriptom účinky záření   MeSH
• vztah dávky záření a odpovědi MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Population ageing presents a challenge to oncological care due to the particularities of cancer treatment in this population. We evaluate cancer epidemiology, treatment and survival, in the Czech Republic by age groups. Data published by the Czech National Cancer Registry from the years 2006 to 2010 were used for this study. The following cancer types were evaluated: colorectal, pancreatic, head and neck, lung, skin melanoma, breast, gynaecological, prostate, kidney and stomach cancers. The following data were recorded and analysed: crude incidence by 5-year age group; dynamics of crude incidence rates in the age group ≥70 years; disease stage; percentage of patients treated by surgery, radiotherapy and chemotherapy; and age standardised 1-year mortality and 5-year relative survival according to age group. Patients over age 70 accounted for 41% and 46%, respectively, of the cancer incidence and mortality of the whole population. Anticancer therapies are significantly less common in patients over age 70 (P < 0.050), with the exception of skin melanoma. Survival was markedly worse in older patients (P < 0.050) when radical treatment modalities were significantly underused (P < 0.050). In the Czech Republic, the crude cancer incidence in seniors is increasing. In general, elderly patients are undertreated, with worse treatment results compared with younger patients.

• MeSH
• analýza přežití MeSH
• incidence MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory epidemiologie   mortalita   MeSH
• prevalence MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• věkové rozložení MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

To quantitatively evaluate the extent to which fiducial-based image-guidance improves dose coverage of the target volume and sparing of critical organs for prostate cancer patients treated with intensity modulated radiotherapy (IMRT) and determination of planning margins by original approach of detailed daily dose volume histogram (DVH) and patient's position correction analysis. Sixty-two patients divided in two groups (clinical target volume (CTV) → planning target volume (PTV) margin 10 and 7 mm) were treated with IMRT using implanted fiducial markers. Each patient's treatment fraction was recalculated as it would have been treated without fiducial-guided positioning. For both plans (IGRT and non-IGRT), equivalent uniform doses (EUD), maximal and minimal doses for target volumes, normal tissue complication probability (NTCP), maximum and mean doses for organs at risk and the whole DVH differences were assessed. In the group with 10 mm margins, the only significant difference was worse rectal NTCP by 4.5%, but the CTV dose coverage remained at the same level. Recalculated plans with 7 mm margin could not achieve the prescribed target volume coverage, and the EUD decreased by 3.7 and 0.6 Gy for PTV and CTV, respectively. Desired CTV → PTV margin for non-IGRT plans should be no lower than 12 mm to guarantee 95% instances when delivered dose to CTV maintain as planned, for IGRT plans decrease this requirement to 2 mm. Prostate IMRT strategies involving margin reduction below 7 mm require image-guidance to maintain the planned dose coverage. Using fiducial-based image-guidance and large margins seems to be superfluous.

• MeSH
• celková dávka radioterapie MeSH
• lidé MeSH
• nádory prostaty patologie   radioterapie   MeSH
• plánování radioterapie pomocí počítače * MeSH
• počítačová rentgenová tomografie MeSH
• radioterapie s modulovanou intenzitou metody   MeSH
• zaměřovací značky pro radioterapii MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: To present a single case report on successful radiotherapy treatment of lacrimal gland infiltration in patient with Sjögren΄s syndrome. BACKGROUND: Radiotherapy is occasionally used for the treatment of benign disorders. There is no report on use of radiotherapy for local treatment of the Sjögren΄s syndrome in the literature. METHODS: Female patient with lacrimal gland involvement as a part of Sjögren΄s syndrome with diplopia and visus deterioration was treated by radiotherapy with eye shielding. RESULTS: Regression of the infiltration with full restoration of visus and minimal acute radiation reaction was achieved. CONCLUSION: A case report of successful use of local radiotherapy in the treatment of lacrimal gland affected by Sjögren΄s syndrome is presented (Fig. 3, Ref. 6). Full Text in PDF www.elis.sk.

• MeSH
• dospělí MeSH
• lidé MeSH
• nemoci slzného ústrojí radioterapie   MeSH
• Sjögrenův syndrom radioterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

PURPOSE: The aim of the present study was to examine the effect of neoadjuvant chemoradiation on tumor epidermal growth factor receptor (EGFR) expression in patients with locally advanced rectal adenocarcinoma. PATIENTS AND METHODS: A total of 53 patients with rectal adenocarcinoma (clinical stages II and III) were studied. Neoadjuvant treatment consisted of 50.4 Gy/28 fractions external radiation with concomitant continuous 5-fluorouracil. Surgical resection was performed 4-6 weeks after the chemoradiation. EGFR expression in the pretreatment biopsies and in the resected specimens was assessed with immunohistochemistry. RESULTS: Patients with an increase of EGFR expression during chemoradiation had significantly shorter disease-free survival (DFS; p = 0.003) and overall survival (OS; p = 0.005) compared to patients with either no change or decrease in EGFR expression. The 5-year DFS in patients with increased EGFR expression was only 29% compared to 61% in patients without an increase of EGFR expression. Similarly, the 5-year OS of the patients with increased EGFR expression was 29% compared to 66% in patients without an increase of EGFR expression. All recurrences in patients who had an increase of EGFR expression occurred within the first 2 years after the treatment. The increase in EGFR expression was the only significant predictor of DFS (p = 0.007) and OS (p = 0.04) using multivariate Cox regression analysis. CONCLUSION: An increase of EGFR expression during chemoradiation may be associated with significantly shorter DFS and OS. The increase of EGFR could identify a population of patients in whom the effect of the treatment with anti-EGFR therapy should be studied.

• MeSH
• adenokarcinom diagnóza   metabolismus   terapie   MeSH
• adjuvantní chemoradioterapie MeSH
• dospělí MeSH
• erbB receptory metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery metabolismus   MeSH
• nádorové proteiny metabolismus   MeSH
• nádory rekta diagnóza   metabolismus   terapie   MeSH
• neoadjuvantní terapie MeSH
• prognóza MeSH
• reprodukovatelnost výsledků MeSH
• senzitivita a specificita MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH

Radical radiotherapy with concurrent cisplatin-based chemotherapy is an established treatment for cervical cancer patients with stage FIGO IIB and higher. The tumor control can be achieved in 40-80% of patients, the treatment is associated with the risk of late postiradiation complications in 10 - 15% of cases. Detection of the factors predictive for tumor control and late morbidity is a possible direction how to individualize radiotherapy dose and technique. The aim of our review is to summarize results of studies inquiring various molecular markers predicting tumor response to radiotherapy and a risk of late complications. A lot of candidate molecules were evaluated in histochemical studies: membrane receptors (EGFR, HER-2), cell cycle regulators (p53, p21), proliferative markers (Ki-67), hypoxia and angiogenetic factors (HIF, VEGF), HPV status, and others (COX-2), with promising results in some of them (HPV, HIF-1α, Ku80, ATM polymorphism). Microarray studies identified decades of genes with different expression in radiosensitive/radioresistant cervical tumors and sets of genes are able to comletely separate responding and nonresponding tumors, but these sets differ across studies. Further well designed studies will be necessary to achieve results matured for use in clinical practice.

• MeSH
• lidé MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory děložního čípku diagnóza   metabolismus   radioterapie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH