Factors, associated with elevated concentration of soluble carbonic anhydrase IX in plasma of women with cervical dysplasia.

Precancerous lesions of human cervix uteri have a tendency for regression or progression. In cervical intraepithelial neoplasia grade 2 (CINII) case there is an uncertainty if a lesion will progress or regress. The carbonic anhydrase IX (CAIX) enzyme is overexpressed in cervical cancer which is more sensitive to radiotherapy. CAIX is associated with poor prognosis in solid hypoxic tumors. The aim of this study was to determine factors related to elevated soluble CAIX (s-CAIX) in high-grade intraepithelial lesion (HSIL) cases. METHODS: Patients diagnosed with HSIL (N = 77) were included into the research group whereas without HSIL (N = 72)-the control group. Concentration of the soluble CAIX (s-CAIX) in plasma was determined by the DIANA ligand-antibody-based method. C. trachomatis was detected from cervical samples by PCR. Primary outcomes were risk factors elevating s-CAIX level in HSIL group. Non-parametric statistical analysis methods were used to calculate correlations. RESULTS: The s-CAIX level in patients with HSIL was elevated among older participants (rs = 0.27, p = 0.04) and with C. trachomatis infection (p = 0.028). Among heavy smokers with HSIL, the concentration of s-CAIX was higher in older women (rs = 0.52, p = 0.005), but was not related to the age of heavy smokers' controls (τ = 0.18 p = 0.40). CONCLUSION: The concentration of s-CAIX was higher among older, heavy smoking and diagnosed with C. trachomatis patients. All these factors increased the risk for HSIL progression.

Reproductive Factors and Breast Cancer Risk in Lithuanian Women: A Population-Based Cohort Study.

ABSTRACT BACKGROUND: Although the relationship between reproductive factors and breast cancer is internationally proved, reliable data on former USSR countries are scarce. This study examines the association of parity, age at the first childbirth, number of children, and breast cancer risk in Lithuanian women. METHODS: The study that included women from 40 to 79 years old was based on a dataset that was made up linking all records from the 2001 census, all cancer incidence records from the Lithuanian Cancer Registry and all death records from Statistics Lithuania between 6th April 2001 and 31st December 2009. Cox's proportional hazards regression models were used to estimate the hazard ratios (HRs) for parity, age at the first childbirth, and number of children. RESULTS: If compared to nulliparous women, parous women had a lower risk of breast cancer (HR=0.84, 95% CI 0.78-0.89) and this risk further decreased with an increasing number of children. Women who gave birth after the age of 25 had a significantly higher risk of breast cancer. This disadvantage became statistically insignificant or decreased after controlling for total number of children. CONCLUSIONS: Parity and age at the first childbirth are strong predictors of breast cancer risk among Lithu-anian women.

Trends in Breast Cancer Incidence and Stage Distribution Before and During the Introduction of the Mammography Screening Program in Lithuania.

BACKGROUND:: The aim of this study was to analyze the incidence trends of localized and advanced breast cancer (BC) before and during the implementation of the mammography screening program (MSP) in Lithuania. METHODS:: The study period was divided into 2 intervals: the prescreening period (1998-2005) and implementation period (2006-2012). Analysis was performed for 3 age-groups: 0 to 49 years, 50 to 69 (target population), and older than 70. RESULTS:: In all age-groups, the incidence of localized BC has shown a steady increase, while the incidence of advanced stage BC has decreased. In the target population, during the study period, the stage I BC incidence increased statistically significantly by 10.3% per year (from 3.3 per 100 000 in 1998 to 12.2 per 100 000 in 2012). The increase in localized BC was faster in the period before the implementation of the MSP than during the implementation in 2006 to 2012 (10.3% and 5.7%). A slightly statistically significant decrease was observed for advanced BC during the study period (-1.1% per year), while during the implementation of the MSP, significant changes were not seen. CONCLUSIONS:: The results of our study indicate that the implementation of the MSP in Lithuania did not significantly influence trends of localized and advanced BC. Changes observed during the study period, including the prescreening and screening introduction periods, may reflect the general trends in the awareness of BC and improvements in diagnostics.

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.