Advances in thymic carcinoma diagnosis and treatment: a review of literature.

Thymomas account for up to 50 % of anterior mediastinal neoplasms with an incidence of 0.13 per 100,000 person-years in the USA. Thymic carcinoma is a rare malignancy of the thymus gland distinguished from thymomas as it has a more invasive and metastasizing potential conferring poor prognosis. Due to the rarity of thymic carcinoma and the great variety of its histological subtypes, there is no solid evidence on optimal staging, imaging and treatment guidelines. Herein, we systematically review the literature on current clinical practice with regard to diagnostic evaluation, histopathological assessment, management and treatment of squamous thymic carcinoma.

c-MYC and h-TERT co-expression in colon adenocarcinoma: a tissue microarray digitized image analysis.

PURPOSE: c-MYC oncogene is frequently deregulated by amplification in colon adenocarcinoma. c-MYC also activates telomerase by inducing expression of its catalytic subunit (h-TERT). Furthermore, telomerase activation plays a crucial role in tumorigenesis by sustaining cellular immortality. Our aim was to evaluate the significance of c-MYC and h-TERT co-expression in colon adenocarcinoma. METHODS: Sixty paraffin embedded primary colon adenocarcinomas were cored at 1.5 mm diameter and transferred to one microarray block. Immunohistochemistry was performed using anti-h-TERT, and c - MYC antibodies. A quantitative digitized macro was performed to evaluate their expression. RESULTS: c-MYC and h-TERT overexpression was observed in 27 (45%) and 28 (46.6%) cases, respectively. Co-over expression of those genes was observed in 17 (28.3%) cases and found to be statistically significant (p=0.001). The results also showed a strong association between c-MYC and grade of differentiation of the examined neoplasms (p=0.0217rpar;. CONCLUSION: Simultaneous c-MYC and h-TERT deregulation is a relatively frequent genetic event in colon adenocarcinoma. Because c-MYC overexpression is correlated with progressive disease - due to colon adenocarcinoma dedifferentiation - inhibition of its activity combined with h-TERT regulated expression is a new target for novel therapeutic regimens.

Gene numerical imbalances in cytological specimens based on fluorescence/chromogenic in situ hybridization analysis.

Design and development of novel targeted therapeutic strategies is an innovation in handling patients with solid malignancies including breast, colon, lung, head & neck or even pancreatic and hepatocellular carcinoma. For a long time, immunohistocytochemistry (IHC/ICC) has been performed as a routine method in almost all labs for evaluating protein expression. Modern molecular approaches show that identification of specific structural and numerical imbalances regarding genes involved in signal transduction pathways provide important data to the oncologists. Alterations in molecules such as epidermal growth factor receptor (EGFR), HER2/neu, PTEN or Topoisomerase IIa affect the response rates to specific chemotherapeutic agents modifying also patients' prognostic rates. In situ hybridization (ISH) techniques based on fluorescence and chromogenic variants (FISH/CISH) or silver in situ hybridization (SISH) are applicable in both tissue and cell substrates. Concerning cytological specimens, FISH/CISH analysis appears to be a fast and very accurate method in estimating gene/chromosome ratios. In this paper, we sought to evaluate the usefulness of FISH/ CISH analysis in cytological specimens, describing also the advantages and disadvantages of these methods from the technical point of view.

Evaluation of methodology and quality characteristics of systematic reviews in orthodontics.

Systematic reviews (SRs) are published with an increasing rate in many fields of biomedical literature, including orthodontics. Although SRs should consolidate the evidence-based characteristics of contemporary orthodontic practice, doubts on the validity of their conclusions have been frequently expressed. The aim of this study was to evaluate the methodology and quality characteristics of orthodontic SRs as well as to assess their quality of reporting during the last years. Electronic databases were searched for SRs (without any meta-analytical data synthesis) in the field of orthodontics, indexed up to the start of 2010. The Assessment of Multiple Systematic Reviews (AMSTAR) tool was used for quality assessment of the included articles. Data were analyzed with Student's t-test, one-way ANOVA, and linear regression. Risk ratios (RR) with 95% confidence intervals were calculated to represent changes during the years in reporting of key items associated with quality. A total of 110 SRs were included in this evaluation. About half of the SRs (46.4%) were published in orthodontic journals, while few (5.5%) were updates of previously published reviews. Using the AMSTAR tool, thirty (27.3%) of the SRs were found to be of low quality, 63 (57.3%) of medium quality, and 17 (15.5%) of high quality. No significant trend for quality improvement was observed during the last years. The overall quality of orthodontic SRs may be considered as medium. Although the number of orthodontic SRs has increased over the last decade, their quality characteristics can be characterized as moderate.

Correlation between different p53 expression patterns and chromosome 17 imbalances in pancreatic ductal adenocarcinoma based on tissue microarray analysis.

PURPOSE: p53 (gene location: 17p13.1) overexpression is a common event in pancreatic ductal adenocarcinoma (PDAC), a highly aggressive malignant neoplasm. Although specific mechanisms of p53 gene deregulation have been identified, correlation between p53 expression and chromosome 17 gross numerical imbalances (aneuploidy) are under investigation. METHODS: Using tissue microarray technology, 60 paraffin-embedded tissue samples of histologically confirmed primary PDACs were cored and re-embedded to the final recipient block. Immunohistochemistry (IHC) for p53 expression and chromogenic in situ hybridization (CISH) for chromosome 17 numerical alterations were performed. Digital image analysis was applied for p53 expression levels evaluation (Nuclear Labelling Index-NLIs). RESULTS: p53 overexpression was detected in 38/60 (63.3%), whereas chromosome 17 aneuploidy was observed in 21/60 (35%) cases, respectively. Polysomy was identified in 19 cases, whereas monosomy in 2 of them. p53 overall expression was strongly correlated to the stage of the examined tumors (p=0.02). Chromosome aneuploidy was not associated to tumors' stage and grade (p=0.42, p=0.71, respectively). Although overall chromosome 17 centromeric imbalances were not correlated with p53 overexpression (p=0.32), both cases with monosomy demonstrated high expression levels. CONCLUSION: p53 overexpression combined with chromosome 17 numerical imbalances characterizes a significant proportion of PDACs. Because commercially available antip53 antibodies detect mutant and also wild-type protein expression levels, chromosome 17 monosomy maybe is a gross genetic criterion for discriminating them due to point mutation that frequently affects the remaining allele.

Deregulation of EGFR/VEGF/HIF-1a signaling pathway in colon adenocarcinoma based on tissue microarrays analysis.

PURPOSE: Overexpression of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in colon adenocarcinoma (CA) is a frequent event, whereas specific deregulation mechanisms in the corresponding signaling pathways remain under investigation. Our aim was to co-evaluate their expression correlated to the hypoxia inducible factor 1alpha (HIF-1a), which activates the transcription of VEGF gene. METHODS: 60 paraffin-embedded primary CAs were cored at 1.5 mm diameter and transferred to the microarray block. Immunohistochemistry (IHC) was performed using anti-EGFR, -VEGF, and -HIF 1a monoclonal antibodies. Concerning EGFR, quantitative evaluation was based on a semi-automated analysis system. Chromogenic in situ hybridization (CISH) was performed using EGFR gene and chromosome 7 centromeric probes. RESULTS: Protein overexpression was observed in 13/60 (21.6%), 45/60 (75%) and 7/60 (11.6%) cases regarding EGFR, VEGF, and HIF 1a, respectively. CISH analysis detected 4/60 (6.6%) EGFR gene amplified cases, whereas chromosome 7 aneuploidy was identified in 11/60 (18.3%) cases. Significant associations raised correlating stage to chromosome 7 (p=0.024), HIF 1a expression to tumor anatomical location (p=0.019) and also VEGF to HIF 1a expression (p=0.001), whereas EGFR expression was not associated to EGFR gene copies. CONCLUSION: According to our results, chromosome 7 instability is correlated to advanced disease, whereas a significant subset of CAs demonstrates an alternative, non- HIF 1a depended mechanism of VEGF overexpression. Furthermore, EGFR protein overexpression does not predict a specific gene deregulation mechanism.

Adjuvant platinum-based chemotherapy in patients with epithelial ovarian cancer: prognostic factors and final outcome.

PURPOSE: epithelial ovarian cancer (OVCA) prognosis depends on the clinical stage, histological grade and surgical cytoreduction. Our goal was to retrospectively analyze several prognostic factors in relation with the final outcome in patients with OVCA subjected to adjuvant platinum (PL)- based chemotherapy (CT). METHODS: three hundred OVCA patients were treated at the Department of Medical Oncology A', "Metaxa" Cancer Hospital, between 11/1989-3/2010. Of those, analyzed were patients with R0 debulking operation, treated with adjuvant PL-based CT. Their clinico/imaging/pathological findings and serum tumor marker CA 125 levels were analyzed and related to relapse rate (RR), progression-free survival (PFS) and overall survival (OS). RESULTS: out of 53 R0 OVCA patients 35 (66%) experienced long-term PFS (median follow up time 63 months, range 5-195(+)) and 18 (34%) relapsed after a median of 19 months. Fifteen of the 18 relapsing patients were treated with first-line CT. Twelve (80%) of them were PL-sensitive and 3 (20%) PL-resistant. Their median PFS was 9 and 3 months in PL-sensitive and PL-resistant cases, respectively (p=0.073). Statistical analysis of prognostic factors demonstrated FIGO stage and abnormal postoperative CA 125 values as significant. Patients with FIGO stage III had significantly shorter PFS (p=0.002) and OS (p=0.078) than those in earlier stages, and patients with abnormal postoperative CA 125 values had significantly worse PFS (p=0.017) but not OS (p=0.386) than those with normal values. Age, histological subtype and grade did not affect PFS and OS. CONCLUSION: FIGO stage and abnormal postoperative CA 125 have prognostic significance in OVCA patients after R0 surgical therapy and adjuvant PL-based CT. Patients with PL-sensitive disease achieved better results during therapy for relapse.

Treatment with trabectedin: should be indicated to all soft tissue sarcoma histotypes?

Trabectedin is a novel antineoplastic agent approved as monotherapy in patients with advanced soft tissue sarcoma (STS) after failure of standard therapy with anthracyclines or ifosfamide, or patients who are unsuited to receive these agents. Some histotypes of STSs appear to be particularly sensitive to trabectedin, but the sensitivity of some rare STSs histological subtypes to the drug is rather unknown. We report on two patients suffering from infrequent subtypes of STSs, fibrosarcoma and epithelioid sarcoma, who were treated with trabectedin. In these cases the treatment completely failed, and right after the first cycle of trabectedin administration an unusually rapid tumor growth and dissemination was documented. Of note, one of the patients showed objective response to MVIP chemotherapy (methotrexate, etoposide, ifosfamide and cisplatin), after trabectedin failure. Trabectedin activity against several subtypes has not been studied or well-documented due to the rarity and numerous histotypes of STSs. Case studies aiming at the individualization of treatment options against specific STS subtypes will further justify the usage of this agent in clinical practice.

Characterization and in vitro estrogenicity of orthodontic adhesive particulates produced by simulated debonding.

OBJECTIVE: To investigate the structure and composition of ground orthodontic adhesive particulates produced under simulated clinical conditions and assess their estrogenic action in vitro. MATERIALS AND METHODS: A chemically cured and a light-cured adhesive were included in the study. Specimens were prepared by simulating bonding procedures, covering the bracket base surface with cellulose films to detach the full set material. The adhesives prepared under this method were grounded in glass chambers with an 8-fluted tungsten carbide on a high-speed handpiece; a new bur and different chamber was used for each adhesive sample and grindings were performed on different days to avoid contamination of the room. The adhesive particulates produced were subjected to FT-IR spectroscopy for the molecular characterization of particles; scanning electron microscopy for the morphologic condition and structure; and X-ray microanalysis for the elemental composition of the particles. Amounts of the ground adhesives were immersed in saline for 1 month at 37 degrees C. Eluents from solution of the two adhesives were added to media of an estrogen-responsive cell line derived from human breast adenocarcinoma (MCF-7), to assess the estrogenicity. Positive (estradiol and bisphenol-A) and negative (saline) controls were used; all assays were repeated four times and the results were averaged. Estrogenicity data were analyzed with one-way ANOVA and the Tukey test at the .05 level of significance. RESULTS: The study of the composition of particles revealed compounds related to monomers with no major differences noted. Significant structural alterations were observed between the materials studied, with the chemically cured adhesive having larger particles. The ground samples contained Si, Na and Al apparently deriving from fillers, whereas large Ba fillers were identified only in the chemically cured group, whereas no distinct molecular variation was noted between the set material and its corresponding particulate form. Both chemically cured and light-cured adhesives exhibited an estrogenic action through induction of the proliferation rate of MCF-7 cells (160% and 128%, respectively, compared to control). SIGNIFICANCE: Apart from the potentially hazardous action of adhesive particulate aerosol produced by grinding, composite resin particulates may act as endocrinological disruptors.

Three-dimensional assessment of dental casts' occlusal surfaces using two impression materials.

The aim of this study was to assess by means of a three-dimensional computed tomography scanning system the occlusal surface characteristics of dental casts made using two different impression materials. Alginate and polyvinyl siloxane impressions were taken of 20 dental students resulting in 40 dental casts. The casts were paired for each student separately so that each pair consisted of an alginate poured cast and a polyvinyl siloxane poured out cast. The casts were scanned using FlashCT scanner and for each cast, a three-dimensional digital image was obtained. The digitized casts were processed using the three-dimensional imaging software Geomagic Studio 9. A total of 464 paired teeth were digitally separated and superimposed. For each tooth, two measurements were obtained corresponding to the two different impression materials used. The two sets of volumes for all digitally separated teeth were compared and analysed using the Wilcoxon signed test. Larger volume measurements were obtained for teeth separated from alginate poured out casts than from their corresponding ones from polyvinyl siloxane casts (P = 0.005). When the teeth were divided into the groups of incisors, canines and premolars/molars, only the last one exhibited significant difference (P = 0.00). The mean difference between the volumes measured for all 464 teeth separated was 0.041 mm(3) (+/-0.33). The occlusal surfaces of teeth appear differently in dental casts depending on the impression materials used. Impressions of dental casts should be utilized with caution in relation to their research application and in reference with dental wear studies.

Precision of in vivo spectrophotometric colour evaluation of natural teeth.

The aim of the study was to evaluate the precision of a reflectance spectrophotometer during longitudinal assessment of tooth colour in vivo. The spectrophotometric data of five standardized circular areas on the labial surfaces of six teeth (four upper and two lower), from 22 dental students, were recorded on three separate days (1st, 3rd and 30th) employing a repeated-measuring design (n = 3). Total colour differences were calculated according to the equation DeltaEpsilon = [(DeltaL*)(2) + (Deltaa*)(2) + (Deltab*)(2)](1/2). It was found that all measured teeth areas, recorded by the same examiner (DeltaEpsilon(INTRA)), demonstrated minor colour changes during the three different time intervals, which did not exceed in every case the 50:50% perceptibility threshold of DeltaEpsilon = 1, thus indicating a good match. The smallest DeltaEpsilon values were recorded for the upper central incisors, whereas lower central incisors and upper first premolars revealed the most significant colour differences (0.68 +/- 0.21 and 0.70 +/- 0.25 DeltaEpsilon-units, respectively). The central zone of the middle third of each labial tooth surface exhibited the most precise recordings. With regard to interexaminer reproducibility (DeltaEpsilon(INTER)), the mesial and distal areas of all measured teeth presented the most statistically significant colour differences (0.48 +/- 0.15 and 0.50 +/- 0.17 DeltaEpsilon-units, respectively). It is concluded that the spectrophotometer tested in the present study can provide a precise measurement of tooth colour in vivo. However, in rejection of the null hypothesis, the type (posterior teeth, mandibular incisors) and the mesial and distal areas of natural teeth affected the repeatability and reproducibility of intraoral spectrophotometric measurements.

Primary bacteraemia caused by Rhizobium radiobacter in a patient with solid tumours.

A case of Rhizobium radiobacter primary bacteraemia in a patient with solid tumours is reported. Corticosteroid therapy and diabetes mellitus were the predisposing factors. The patient was treated successfully with amikacin and piperacillin/tazobactam. The clinical isolate was identified as R. radiobacter by 16S rRNA gene sequencing. Phytopathogenicity tests and a PCR assay demonstrated that the organism was not a plant pathogen.

In vivo evaluation of two new moisture-resistant orthodontic adhesive systems: a comparative clinical trial.

OBJECTIVE: To evaluate and compare the clinical performance of two new moisture-resistant orthodontic adhesive systems: a chemically-cured composite resin (Unite, 3M Unitek, Monrovia, California, USA) in conjunction with a special moisture-resistant primer (Transbond MIP, 3M Unitek, Monrovia, California, USA); and a fluoride-releasing light-cured compomer (Assure, Reliance Orthodontic Products, Inc., Itasca, Illinois, USA). DESIGN: Randomized controlled clinical trial using the 'split-mouth' technique. SETTING: Department of Orthodontics, Aristotle University of Thessaloniki. SUBJECTS (MATERIALS) AND METHODS: Twenty-five consecutively started patients (13 females and 12 males) requiring fixed appliance orthodontic treatment. INTERVENTIONS: Four-hundred-and-thirty-six stainless steel brackets bonded to all teeth except molars using two different moisture-resistant orthodontic adhesive systems. MAIN OUTCOME MEASURES: Bond failure rates during a period of 9 months were estimated for each adhesive system and the corresponding bracket survival curves were plotted using the Kaplan- Meier product-limit estimate. Bracket survival distributions with respect to adhesive material, tooth location, patient's gender and operator, were then compared by means of a log-rank test. Bond failure interface was determined using the Adhesive Remnant Index. RESULTS: Assure recorded a higher bond failure rate (13.8 per cent) than Unite & MIP (7.3 per cent). The corresponding bracket survival curves were found to be significantly different (P < 0.05). Premolars exhibited higher bond failures than incisors and canines (P < 0.001), while half (49.8 per cent) of the total bond failures occurred during the first 2 months of treatment. The predominant mode of failure was within the bonding material. CONCLUSION: The new moisture-resistant adhesive systems under study were found to be clinically efficient, though Assure exhibited a significantly higher bond failure rate than Unite and Transbond MIP. The higher frequency of adhesive failures observed with Assure might indicate a possible weak point at the adhesive-bracket interface.

In vivo evaluation of a moisture-activated orthodontic adhesive: a comparative clinical trial.

OBJECTIVES: To evaluate and compare the clinical performance of a water-activated, ethyl-cyanoacrylate adhesive to a conventional composite resin. The null hypothesis tested was that there was no difference in bracket survival distribution, over a period of orthodontic treatment, for brackets bonded with either bonding agent. DESIGN: Single center randomized controlled clinical study. SETTING AND SAMPLE POPULATION: Twenty-five consecutive patients (15 females and 10 males) were selected and treated with fixed appliances in a university postgraduate orthodontic clinic. All teeth, but the molars, were bonded with twin stainless steel brackets (n = 429) using a split-mouth technique and random allocation of the two adhesives. OUTCOME MEASURE: Bond failure rates during a period of 9 months were estimated for each adhesive system and the corresponding bracket survival curves were plotted using the Kaplan-Meier product-limit estimate. Bracket survival distributions with respect to adhesive material, tooth location, investigator, and bond failure interface were then compared by means of a log-rank test. Bond failure interface was determined using the Adhesive Remnant Index (ARI). RESULTS: The water-activated bonding material recorded a significantly higher bond failure (22.4%) than the composite resin (5.1%). There were also statistically significant differences in bracket survival distributions between the two adhesives (log-rank test: p < 0.001). Premolars exhibited higher bond failure rates than incisors and canines (p < 0001). The predominant mode of failure was within the bonding material. CONCLUSION: Further investigations focused on the improvement of the physical and mechanical properties of the water-activated bonding system are needed to make it a reliable alternative adhesive for the direct bonding of orthodontic brackets.

Impact factor. A review with specific relevance to orthodontic journals.

The aim of this article is to address the issues of impact factor and circulation with reference to dental and orthodontic journals by discussing various parameters including language, citations, nature of published articles, and scientific domain. Examples from the literature are provided to illustrate the variability of impact factors among periodicals, based on the publicity and scientific area covered, and the impact factor scores are presented together with the circulation of orthodontic periodicals.

Surface characterization of retrieved NiTi orthodontic archwires.

The structure and morphological condition of retrieved NiTi orthodontic archwires was evaluated and any possible alterations in the surface composition of the alloy following 1-6 months in vivo were characterized. NiTi wires (GAC, German Orthodontics, ORMCO) of various cross-sections were collected through a retrieval protocol and were subjected to multi-technique characterization. Optical microscopy revealed islands of amorphous precipitants and accumulated microcrystalline particles. Micro MIR-FTIR investigation of the retrieved samples demonstrated the presence of a proteinaceous biofilm, the organic constituents of which were mainly amide, alcohol, and carbonate. Scanning electron microscope and X-ray microanalysis showed that the elemental species precipitated on the material surface were Na, K, Cl, Ca, and P, forming NaCl, KCl, and Ca-P precipitates. Increased intra-oral exposure was consistently associated with the presence of a mature film, while evidence of alloy delamination, pitting, and crevice corrosion, as well as a notable reduction in the alloy grain size was observed. Intra-oral exposure of NiTi wires alters the topography and structure of the alloy surface through surface attack in the form of pitting or crevice corrosion or formation of integuments. Further in vivo research is required to resolve the implications of the described ageing pattern in the corrosion resistance of the alloy, the potential for nickel leaching, as well as bracket-archwire friction variants.

Random errors in localization of landmarks in postero-anterior cephalograms.

The aim of the present study was to evaluate the random error in localization of the most common landmarks in postero-anterior cephalograms (PAC). The study took place at the Department of Orthodontics of Aarhus University during the period 1993-1995. The material consisted of 30 standardized PAC taken in natural head position. Five examiners had to identify 34 landmarks on each cephalogram. Subsequently, all examiners had to identify again the same 34 landmarks on one randomly selected cephalogram five times with a time interval of at least 24 hours. All landmarks were digitized, related to an X-Y co-ordinate system, and an arithmetical mean was calculated. The accuracy of digitizing was evaluated by digitizing one randomly selected cephalogram 10 times. The main findings of this study are: (1) The digitizing error is negligible compared to the errors introduced by landmark identification. (2) Each landmark has its own characteristic pattern of variance, which is very similar on both sides. (3) Significant differences in accuracy exist between the various postero-anterior landmarks. The six most accurate landmarks are mastoid left (l) and right (r), latero-orbitale (l) and (r), and antegonion (l) and (r). The six least accurate landmarks are coronoid (l) and (r), condylar (l) and (r), and mandibular foramen (l) and (r). (4) A significant difference in the accuracy of landmark identification between the five examiners was only seen for seven of the 34 landmarks. (5) No evidence was found that one examiner was consistently better/worse than the others. (6) No improvement in the accuracy was found after repeated identification, thus there seems to be no short-term 'learning process'. Refereed Paper