The preoperative exclusion of thyroid carcinoma in multinodular goiter: Dynamic contrast-enhanced magnetic resonance imaging versus ultrasonography-guided fine-needle aspiration biopsy.

BACKGROUND: We compared the diagnostic values of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and ultrasonography (USG)-guided fine-needle aspiration biopsy (FNAB) in the detection of thyroid carcinoma associated with multinodular goiter. METHODS: USG-guided FNAB and DCE-MRI were performed consecutively on 26 patients who had multinodular goiter with dominant nodules and clinical suspicion of malignancy. DCE-MRI findings, cytodiagnosis, and final histopathologic results were correlated. We compared the sensitivity, specificity, diagnostic accuracy, and positive (PPV) and negative predictive values (NPV) of DCE-MRI and USG-guided FNAB. RESULTS: Of 57 nodules in 26 patients, 16, 37, and 4 nodules showed delayed, plateau, and rapid washout patterns, respectively. Thyroid carcinoma was found in 8 patients (31%). Delayed washout pattern in a nodule was correlated with the histologic diagnosis of thyroid carcinoma (P < .001). None of the nodules with thyroid carcinoma had a plateau or rapid washout pattern. The sensitivity and NPV of DCE-MRI to diagnose thyroid carcinoma were greater when compared with those in USG-guided FNAB (100 vs 71.4%, and 100 vs 91.7%, respectively; P < .001). CONCLUSION: When other diagnostic methods are inconclusive, DCE-MRI is superior to USG-guided FNAB to exclude thyroid carcinoma in patients with multinodular goiter.

Expression of bcl-2 in papillary thyroid cancers and its prognostic value.

PURPOSE: Papillary thyroid cancer has a good prognosis. This favourable prognosis may be attributed to the apoptotic tendency of the cancer cells. This study aims to evaluate the expression of bcl-2, which is an antidote of apoptosis, and aims to evaluate the value of bcl-2 as a prognostic marker in papillary thyroid cancer. MATERIAL-METHODS: Bcl-2 expression in the archival materials of 31 patients with papillary thyroid cancer was examined with immunohistochemical methods using bcl-2 and p-53 stains. The results were compared with 31 normal thyroid tissue specimens, which consisted of the contralateral lobes of these patients. The results were then analyzed in accordance with the clinical features of the patients. RESULTS: Thirty (96.7%) patients of the control group were positive for bcl-2 whilst one (3.3%) was negative. The staining for bcl-2 was positive in 12 (%75) patients with microcarcinomas (p < 0.05) and 13 (86.6%) with papillary cancers (p > 0.05). Two cases of the papillary cancer group were admitted to the hospital with local recurrence (6.4%) and both were positive for bcl-2 (p > 0.05). All cases (4/31), whose MACIS scores were higher than 7 were positive for bcl-2. Twenty-one of 27 cases whose MACIS scores were lower than 7 (77.7%) were positive for bcl-2 (p > 0.05). All tumours of this series were negative for p-53 immunstaining. CONCLUSION: The rate of bcl-2 expression in microcarcinomas of papillary thyroid cancer decreases when compared to normal thyroid tissue. This may be an early sign of oncogenesis, and a reason for the favourable prognosis in microcarcinomas. However, bcl-2 cannot be used as a prognostic marker.

What really affects the incidence of central venous catheter-related infections for short-term catheterization?

Central venous catheterization is one of the important sepsis reasons in surgical patients. In this randomized controlled study, the effect of the frequency and type of catheter site care, as well as age, coexisting malignancy or diabetes mellitus, total parenteral nutrition administration and antibiotics use, on central venous catheter infection was investigated. Seventy-two single-lumen polyurethane catheters were included. In group I (n: 33), a transparent occlusive dressing was applied to the insertion site and not removed for 7 days unless there were signs of local infection. In group II (n: 39), daily site care was done with povidone-iodine 10% solution and a new sterile gauze was applied. Chi-square, linear correlation and multiple regression tests were used for statistical analysis. Mean duration of catheters was 8 +/- 4 days. There was no catheter-related sepsis. Ten (13.9%) patients had positive catheter tip cultures of whom three had site infection as well. The incidence of site and tip infections were not significantly different in group I and II (p > 0.05). Site infection and age younger than 60 years significantly increased the rate of tip infection (p: 0.004 and p: 0.02 respectively). Total parenteral nutrition administration was associated with higher rate of tip infection (p: 0.06). Coexisting malignancy or diabetes mellitus, duration of catheter and antibiotics use did not have any significant effect on the rate of central venous catheter infections (p > 0.05). In conclusion, we observed that the frequency of insertion site care and the type of dressing applied to the site had no significant effect on the rate of CVC infection. Insertion site infection was the most significant factor increasing the incidence of catheter tip infection. The use of the CVC for total parenteral nutrition facilitated tip infection as well.

Flow cytometric analysis and confocal imaging of anticancer alkylaminoanthraquinones and their N-oxides in intact human cells using 647-nm krypton laser excitation.

Flow cytometry and laser-scanning confocal fluorescence microscopy have been used in the study of the pharmacodynamics, in single intact cells, of two novel alkylaminoanthraquinones (AQ4 and AQ6), structurally based upon the mid-red excitable but very weakly fluorescent anticancer agent mitoxantrone, together with their respective N-oxide derivatives (AQ4NO and AQ6NO). The drug design rationale was that N-oxide modifications generates prodrug forms suitable for selective bioreductive-activation in hypoxic tumor cells. DNA-binding ranked in the order of mitoxantrone > AQ6 > AQ4 > AQ6NO >> AQ4NO. Using both cytometric methods a similar ranking was found for whole cell and nuclear location in human transformed fibroblasts. However, AQ6 showed enhanced nuclear uptake compared with mitoxantrone, in keeping with its greater capacity to inhibit DNA synthesis. Partial charge neutralisation by N-oxide derivatization resulted in loss of DNA synthesis inhibition but retention of the ability to accumulate in the cytosol, an important property for prodrug development. We conclude that both flow cytometry and confocal imaging revealed biologically significant differences between analogues for subcellular distribution and retention properties. The study demonstrates the potential for these complementary 647-nm krypton laser line-based fluorometric methods to provide relevant structure-activity information in anthraquinone drug-design programmes.

DNA topoisomerase II-dependent cytotoxicity of alkylaminoanthraquinones and their N-oxides.

We studied the role of DNA topoisomerase II in the biological actions of a series of novel alkylaminoanthraquinones, including N-oxide derivatives designed as prodrugs liable to bioreductive activation in hypoxic tumour cells. Drug structures were based upon the DNA-binding anticancer topoisomerase II poison mitoxantrone with modifications to the alkylamino side chains. The agents included AQ4, 1,4-bis{[2-(dimethylamino)ethyl] amino}5,8-dihydroxy-anthracene-9,10-dione, and AQ6, 1{[2-dimethylamino)-ethyl]amino}4-{[2[(hydroxyethyl)amino]ethyl]- amino}5,8-dihydroxy-anthracene-9,10-dione, together with the corresponding mono-N-oxide (AQ6NO) and di-N-oxide (AQ4NO). The R3N(+)-O- modification renders the terminal nitrogen group electrically neutral and was found to reduce AQ6NO or effectively abolish AQ4NO-DNA binding. Comparative studies were carried out using two SV40-transformed fibroblast cell lines, MRC5-V1 and AT5BIVA, the latter being a relative overproducer of DNA topoisomerase II alpha. The inhibition of DNA topoisomerase II decatenation activity ranked according to DNA-binding capacity. A similar ranking was found for drug-induced DNA-protein cross-linking in intact cells, depending upon topoisomerase II availability. Inhibition of DNA synthesis in S-phase synchronized cultures ranked in the order of AQ6 > mitoxantrone > > AQ6NO and was independent of topoisomerase II availability. Cytotoxicity of acute 1-h exposures for all agents except the inactive AQ4NO was enhanced in the topoisomerase II-overproducing cell line. The results indicate an important role for enzyme targeting in anthraquinone action. However, DNA synthesis inhibition and cytotoxicity were greater than expected for AQ6, given its topoisomerase- and DNA-interaction properties, and parallel studies have provided evidence of an additional role for enhanced subcellular accumulation and nuclear targeting. The inactivity of AQ4NO and the retention of only partial activity of AQ6NO, allied with the effective topoisomerase II-targeting and high cytotoxic potential of their presumed metabolites, favour their use as prodrugs in tumour cells with enhanced bioreductive potential.