Urine Molecular Biomarkers for Detection and Follow-Up of Small Renal Masses.

Active surveillance (AS) is the best strategy for small renal masses (SRMs) management; however, reliable methods for early detection and disease aggressiveness prediction are urgently needed. The aim of the present study was to validate DNA methylation biomarkers for non-invasive SRM detection and prognosis. The levels of methylated genes TFAP2B, TAC1, PCDH8, ZNF677, FLRT2, and FBN2 were evaluated in 165 serial urine samples prospectively collected from 39 patients diagnosed with SRM, specifically renal cell carcinoma (RCC), before and during the AS via quantitative methylation-specific polymerase chain reaction. Voided urine samples from 92 asymptomatic volunteers were used as the control. Significantly higher methylated TFAP2B, TAC1, PCDH8, ZNF677, and FLRT2 levels and/or frequencies were detected in SRM patients' urine samples as compared to the control. The highest diagnostic power (AUC = 0.74) was observed for the four biomarkers panel with 92% sensitivity and 52% specificity. Methylated PCDH8 level positively correlated with SRM size at diagnosis, while TFAP2B had the opposite effect and was related to SRM progression. To sum up, SRMs contribute significantly to the amount of methylated DNA detectable in urine, which might be used for very early RCC detection. Moreover, PCDH8 and TFAP2B methylation have the potential to be prognostic biomarkers for SRMs.

Analysis of prognostic factors for melanoma patients.

Introduction. Melanoma is the most dangerous form of skin cancer. Morbidity from melanoma is increasing every year. Previous studies have revealed that there are some demographic and clinical factors having effect on melanoma survival prognosis. Aim of the study. Purpose of our study was to assess melanoma survival depending on prognostic factors, such as age, sex, stage, depth, histology and anatomical site. Materials and methods. We investigated melanoma-specific survival up to 10 years in 85 primary cases of melanoma from diagnosis at the National Cancer Institute in 2006. Analysis was performed for one-, five-, and ten-year survival. The data were processed with Microsoft Excel, data analysis was conducted using SPSS® software. Results. Melanomas diagnosed at stage IV or thicker than 4.00 mm had lower survival (five-year survival: 12.5% and 26.66%, respectively). A significant survival difference was observed among the different stages (p = 0.003) and different depths (p = 0.049) of melanoma. Ten-year survival was 32% for men and 61% for women, but melanoma-specific survival dependent on sex did not have a statistically significant difference (p = 0.121). In persons diagnosed at the age of 65 or older, ten-year survival was lower than in those of 40-64 years of age and in the age group of 15-39 years (44.44% and 26.66%, respectively), but melanoma-specific survival in different age groups did not have a statistically significant difference (p = 0.455). Back/breast skin melanoma had lower ten-year survival (37.03%) than other anatomic sites. Nodular melanoma had the poorest five-year and ten-year melanoma-specific survival among histological subtypes (51.67% and 38.75%). The differences between melanoma localizations (p = 0.457) and histological types (p = 0.364) were not statistically significant. Conclusions. Lower melanoma-specific survival rates were observed among patients diagnosed at a late stage, older age, and when melanomas were thicker than 4.00 mm. Female and younger patients had better melanoma-specific survival than men and older people, and these differences were statistically significant. Melanoma diagnosed at an early stage and of a small depth had higher survival rates. Back/breast skin melanoma had poorer prognosis than other anatomic sites. Nodular melanoma had the lowest melanoma-specific survival, while superficial spreading or lentigo maligna had the best prognosis among histological subtypes. However, differences in melanoma survival in different sex and age groups, localizations and histological types were not statistically significant.

The role of different PI-RADS versions in prostate multiparametric magnetic resonance tomography assessment.

Background. Standardised Prostate Imaging Reporting and Data System (PI-RADS) guidelines for the assessment of prostate alterations were designed for the assessment of prostate pathology. Published by the ESUR in 2012, PI-RADS v1 was based on the total score of different MRI sequences with subsequent calculation. PI-RADS v2 was published by the American College of Radiology in 2015 and featured different assessment criteria for prostate peripheral and transitory zones. Aim. To assess the correlations of PI-RADS v1 and PI-RADS v2 with Gleason score values and to define their predictive values of the diagnosis of prostate cancer. Materials and methods. A retrospective analysis of 66 patients. Prostate specific antigen (PSA) value and the Gleason score (GS) were assessed. One the most malignant focal lesion was selected in the peripheral zone of each lobe of the prostate (91 in total). Statistical analysis was carried out applying SPSS software, v.23, p < 0.05. Results. Focal lesions assessed by PI-RADS v1 score: 10% - 1, 12% - 2, 41% - 3, 23% - 4, 14% - 5. Assessment applying PI-RADS v.2: 20% - 1, 7.5% - 2, 26%, 29.5%, and 17% were assessed by 3, 4, and 5 scores. Statistically relevant correlation was found only between GS and PI-RADS (p = 0.033). The positive predictive value of both versions of PI-RADS - 75%, negative predictive value of PI-RADS v1 - 46%, PI-RADS v2 - 43%. Conclusions. PI-RADS v1 was more statistically relevant in assessing the grade of tumour. Prediction values were similar in both versions.

Optimal differentiation of high- and low-grade glioma and metastasis: a meta-analysis of perfusion, diffusion, and spectroscopy metrics.

INTRODUCTION: To perform a meta-analysis of advanced magnetic resonance imaging (MRI) metrics, including relative cerebral blood volume (rCBV), normalized apparent diffusion coefficient (nADC), and spectroscopy ratios choline/creatine (Cho/Cr) and choline/N-acetyl aspartate (Cho/NAA), for the differentiation of high- and low-grade gliomas (HGG, LGG) and metastases (MTS). METHODS: For systematic review, 83 articles (dated 2000-2013) were selected from the NCBI database. Twenty-four, twenty-two, and eight articles were included respectively for spectroscopy, rCBV, and nADC meta-analysis. In the meta-analysis, we calculated overall means for rCBV, nADC, Cho/Cr (short TE-from 20 to 35 ms, medium-from 135 to 144 ms), and Cho/NAA for the HGG, LGG, and MTS groups. We used random effects model to obtain weighted averages and select thresholds. RESULTS: Overall means (with 95% CI) for rCBV, nADC, Cho/Cr (short and medium echo time, TE), and Cho/NAA were: for HGG 5.47 (4.78-6.15), 1.38 (1.16-1.60), 2.40 (1.67-3.13), 3.27 (2.78-3.77), and 4.71 (3.24-6.19); for LGG 2.00 (1.71-2.28), 1.61 (1.36-1.87), 1.46 (1.20-1.72), 1.71 (1.49-1.93), and 2.36 (1.50-3.23); for MTS 5.06 (3.85-6.27), 1.35 (1.06-1.64), 1.89 (1.72-2.06), 3.14 (1.57-4.72), (Cho/NAA was not available). LGG had significantly lower rCBV, Cho/Cr, and Cho/NAA values than HGG or MTS. No significant differences were found for nADC. CONCLUSIONS: Best differentiation between HGG and LGG is obtained from rCBV, Cho/Cr, and Cho/NAA metrics. MTS could not be reliably distinguished from HGG by the methods investigated.

5-aminolevulinic-acid-based fluorescence spectroscopy and conventional colposcopy for in vivo detection of cervical pre-malignancy.

BACKGROUND: Sensitized fluorescence diagnostics are based on selective accumulation of photosensitizer in the tissue where carcinogenesis has started. The present study compared topical 5-aminolevulinic acid (5-ALA)-based fluorescence spectroscopy (FS) in vivo with conventional colposcopy for cervical intraepithelial neoplasia (CIN) detection. METHODS: We enrolled 48 patients who were referred for colposcopy because of high-grade changes in cervical cytology. Every inspected cervix was divided in to quadrants, and there were 174 quadrants included in the study. Each patient had a cytological smear, colposcopy, FS and histopathological analysis. For FS, 3% 5-ALA cream was used topically and after an average 135 min incubation, fluorescence spectra were recorded from the cervix in vivo. FS and colposcopy results were correlated with histopathology. RESULTS: All spectra were evaluated by a ratio of the protoporphyrin IX fluorescence intensity at 634 nm and autofluorescence intensity at 510 nm. For proper grouping of low-risk and high-risk cases, a threshold of 3.87 was calculated. Data per quadrant showed that FS had higher sensitivity than colposcopy (71.7% vs 67.4%) but specificity was greater for colposcopy (86.6% vs 75.6%). Combination of the methods showed higher sensitivity (88.0% vs 67.4%) but reduced specificity (88.0% and 69.5%), but it had the highest number of correctly identified high-risk changes and the highest (79.3%) accuracy. Data for each patient showed FS sensitivity of 91.2%, which was greater than for colposcopy (88.2%). Higher overdiagnosis resulted in decreased specificity for fluorescence methodology-71.4% versus 78.6% for colposcopy. In both cases, accuracy was 85.4% and effectiveness was >80%, which means that both methods can be used to determine high-risk cervical intraepithelial neoplasia. The diagnostic sensitivity of 97.1% for this complementary diagnosis indicates that it could be the best choice for detection of high-risk changes. CONCLUSIONS: 5-ALA-based FS is an objective method, requiring short-term administration for appropriate fluorescence measurements. FS is a promising diagnostic tool with similar accuracy as colposcopy but with the potential advantage of providing objective results.

5-Aminolevulinic acid-based fluorescence diagnostics of cervical preinvasive changes.

The purpose of this article is to review the diagnostic possibilities of 5-aminolevulinic acid (5-ALA)-based fluorescence diagnosis of preinvasive cervical changes. Reviewed papers were selected from the PubMed database with keywords combining the terms individual cervical neoplasia and fluorescence diagnostics. The regular colposcopy procedure lacks specificity; therefore, new methods are continually sought for superior diagnosis of cervical pathology. 5-ALA-based fluorescence diagnostics is under investigation as an up-to-date diagnostic technique for cervical intraepithelial neoplasia (CIN). This method is grounded on the topical or systemic application of 5-ALA, which induces excess production of the endogenous photosensitizer protoporphyrin IX (PpIX) in tissues where carcinogenesis has begun. The conversion of PpIX to the heme is less efficient in tumors; therefore, higher amounts of PpIX tend to accumulate in premalignant and malignant tissues. Illumination with light of the appropriate wavelength initiates excitation of PpIX fluorescence, which in turn helps to localize PpIX-rich areas and identify potentially malignant tissues. A number of investigations suggest that because of its high selectivity for tumors and low toxicity to healthy tissues, 5-ALA-based diagnosis seems a promising tool for the noninvasive identification of cervical intraepithelial neoplasia.

Gliomatosis cerebri.

Gliomatosis cerebri is a rare diffusely infiltrating glial tumor involving two or more lobes and is frequently is bilateral. Infiltrative extent of tumor is out of proportion to histological and clinical features. We present a case in which finally the diagnosis of gliomatosis cerebri was made. In this case, computed tomography showed that midline structures were insignificantly shifted to the left, there was a mild dilatation of lateral ventricles more expressed on the right, and no pathologic changes of brain tissue density were found. On magnetic resonance tomography, T2W/SE and T2W/FLAIR images revealed zones of hyperintense signal, spreading with time, through several lobes of the brain with no enhancement on T1W images. Diagnosis of gliomatosis cerebri was suspected, stereotaxic biopsy was performed, and pathological examination revealed changes typical of diffuse glial tumor. In this article, changes typical of gliomatosis cerebri seen in other radiological methods such as computed tomography, magnetic resonance spectroscopy, dynamic contrast-enhanced T2*-weighted magnetic resonance, and positron emission tomography also are discussed.

The value of prognostic factors for uterine cervical cancer patients treated with irradiation alone.

BACKGROUND: The aim of our study was to investigate and evaluate the prognostic value of and correlations between preclinical and clinical factors such as the stage of the disease, blood Hb level before treatment, size of cervix and lymph nodes evaluated by CT, age, dose of irradiation and duration of radiotherapy related to overall survival, disease-free survival, local control and metastases-free survival in cervical cancer patients receiving radiotherapy alone. METHODS: 162 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIA-IIIB cervical carcinoma treated with irradiation were analysed. Univariate and multivariate analyses using the Cox regression model were performed to determine statistical significance of some tumor-related factors. RESULTS: The Hb level before treatment showed significant influence on overall survival (p = 0.001), desease free survival (p = 0.040) and local control (p = 0.038). The lymph node status (>10 mm) assessed on CT had impact on overall survival (p = 0,030) and local control (p = 0,036). The dose at point A had impact on disease free survival (p = 0,028) and local control (p = 0,021) and the radiotherapy duration had showed significant influence on overall survival (p = 0,045), disease free survival (p = 0,006) and local control (p = 0,033). CONCLUSION: Anemia is a significant and independent prognostic factor of overall survival, disease-free survival and local control in cervical cancer patients treated with irradiation. The size of lymph nodes in CT is an independent prognostic factor for overall survival and local control in cervical cancer patients. The size of cervix uteri evaluated by CT has no prognostic significance in cervical cancer patients treated with radiotherapy. The prognostic value of FIGO stage of cervical cancer is influenced by other factors, analyzed in this study and is not an independent prognostic factor.

[Importance of dosimetric factors predicting radiation toxicity in lung cancer treatment]. / Plauciu pospindulinio toksiskumo dozimetriniu prognoziniu faktoriu reiksme gydant plauciu vezi.

OBJECTIVE: To evaluate prognostic importance of dosimetric parameters (V20, V30 and V40) in the incidence of lung radiation toxicity caused by external-beam radiation therapy in patients with lung cancer. MATERIAL AND METHODS: A total of 82 patients with lung cancer were analyzed prospectively. They were treated in the Oncology Institute of Vilnius University from 2002 to 2005. Three-dimensional conformal radiotherapy was administered to all patients; radiation dose was > or =50 Gy, delivered in daily fractions of 2 Gy. All patients received concurrent chemotherapy and part of them - surgery. All patients were evaluated before radiation therapy and after 3-, 6-, and 12-month follow-up. V20, V30, and V40 were calculated from dose-volume histograms using the Eclipse(TM) radiotherapy treatment planing system. Based on radiological findings and clinical symptoms radiation-induced lung injury (radiation pneumonitis and radiation fibrosis) was diagnosed. RESULTS: Nearly half of patients (48%) developed grade < or =2 pulmonary toxicity according to the Subjective, Objective, Management and Analytic/Late Effects on Normal Tissues (SOMA/LENT) scale. The percentage volume of normal lung tissue receiving >20 Gy dose was 38%, >30 Gy--25%, and >40 Gy--18%. In patients free of radiation toxicity V20 was 30%, V30--22%, and V40--18%, and in patients with radiation-induced pulmonary toxicity V20 was 48%, V30--30%, and V40--18%. CONCLUSIONS: Dosimetric parameters V20, V30, and V40 are significant predictive factors for radiation-induced pulmonary toxicity. At this time planned V20 and V30 are too high and they should be minimized in order to reduce radiation-induced pulmonary toxicity.

Dose coverage evaluation for lung cancer radiation therapy.

UNLABELLED: Purpose of the study was to evaluate adequacy of target volume coverage with conventional two-dimensional radiotherapy; and to estimate potential of three-dimensional conformal radiotherapy for increasing dose to the target. MATERIAL AND METHODS: Analysis was performed for 34 lung cancer patients referred for curative intend two-dimensional radiation therapy. For the same patients two independent specialist teams created conventional two-dimensional plans according to "gold standard" radiotherapy and three-dimensional conformal plans. Evaluation of target coverage adequacy and normal tissue complication probability parameters was performed on two-dimensional isodose distributions overlay over outlined clinical target volumes. Maximum total dose for three-dimensional conformal radiotherapy was estimated keeping normal tissue complication probability on the same level as for two-dimensional plans. Conformity was evaluated. RESULTS: For two-dimensional planning maximum target dose was on average 52 Gy (3 Gy 1 standard deviation). Clinical target volumes coverage was poor for most plans; 95% isodose surface covers 57%. This percentage was consistent with 1 standard deviation of 10-17%. Minimum target dose was low - 5-10% of prescribed dose. Three-dimensional conformal radiotherapy allows increasing dose to clinical target volume with elective nodes irradiation up to 68-72 Gy and up to 78-90 Gy without it. Conformity of clinical target volume coverage was acceptable for all patients; 95% isodose surface covered on average 95% of target. CONCLUSION: Three-dimensional conformal radiotherapy allows increasing of total dose to the target keeping tolerable dose to functional tissues for most patients. However, only combinations of modern imaging, planning and delivery techniques enable providing adequate and homogeneous clinical target volume coverage with therapeutically significant dose for lung tumors.