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.

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.

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.

Short-term functional alterations in the stomatognathic system after orthodontic-surgical management of skeletal vertical excess problems.

The aim of the present investigation was to study the functional alterations in the stomatognathic system following orthodontic-surgical management of skeletal vertical excess problems. The sample comprised 43 patients who received combined orthodontic-surgical treatment including bilateral vertical ramus osteotomy for posterior repositioning and counterclockwise rotation of the mandible (n = 26) or Le Fort I osteotomy for maxillary impaction (n = 17). All subjects were examined within 1 week before operation and 6 months postsurgery. Methods of examination included: (a) evaluation of dysfunction by means of a clinical index, (b) measurement of mandibular range of motion, (c) assessment of the number and intensity of occlusal contacts, and (d) tomographic evaluation of condyle-fossa relationships. The results of the study indicated that postoperatively (a) there was an increase of patients with dysfunction in the mandibular osteotomy group and a decrease of patients with dysfunction in the maxillary osteotomy group; (b) the maximum interincisal opening decreased significantly in the mandibular osteotomy group; (c) there was a significant increase in the number and intensity of occlusal contacts in both groups; and (d) the shortest posterior and anterior interarticular distances increased significantly in the mandibular osteotomy group.

Evaluation of impacted canines by means of computerized tomography.

The precise localization of impacted canines is of paramount importance in formulating the diagnosis and treatment plan. Conventional radiographic techniques for evaluating impacted canines have a major shortcoming, namely, the superimposition of all structures on the film, which often makes it difficult to distinguish detail. Computerized tomography provides excellent tissue contrast, eliminating blurring and overlapping of adjacent teeth.

Transverse dentofacial structure of young men who have undergone surgical correction of unilateral cleft lip and palate: a posteroanterior cephalometric study.

The transverse dentofacial structure of 34 young adult males with unilateral cleft lip and palate, studied by means of posteroanterior cephalograms, was compared to that of a normal sample of 102 young adult males. All cleft patients had been treated surgically and orthodontically in accordance with a standardized protocol. Orthognathic surgical treatment was carried out when growth had ended in a few subjects. In studying the posteroanterior cephalograms, eight lengths, 10 ratios, and three angular variables were used. Comparison of the cephalometric values of the subjects with cleft palate and the normal sample of young adult males indicated (1) the absence of any significant differences in angular variables describing the transverse dentoalveolar relationships in the maxillary and mandibular incisal regions as well as the mandibular position; (2) the absence of any significant differences in the ratios of the nasal, maxillary, and mandibular widths to the interorbital width; (3) the presence, in the cleft group of significantly decreased ratios of maxillary intermolar width to interorbital width, mandibular intermolar width to interorbital width, maxillary intermolar width to mandibular intermolar width, and maxillary intermolar width to maxillary width; (4) the presence, in the cleft group, of a significantly increased ratio of innerorbital width to interorbital width; and (5) significant correlations between the maxillary and mandibular molar widths in the cleft group.

Validity of computerized predictions of dentoskeletal and soft tissue profile changes after mandibular setback and maxillary impaction osteotomies.

The aim of the present investigation was to evaluate the validity of the predictions of a computerized cephalometric system (Dentofacial Planner) regarding dentoskeletal and soft tissue profile changes after mandibular setback and maxillary impaction osteotomies. Tracings of lateral cephalograms taken at the end of preoperative orthodontics (within 1 week before surgery) and approximately 1 year after the operation were digitized and entered into the Dentofacial Planner. For the mandibular setback group, the computerized predictions tended to place the mandible less posteriorly than the actual situation and to significantly underestimate the mandibular plane angle, the total anterior skeletal and soft tissue facial heights, the lower anterior skeletal facial height, and the upper lip height. In the maxillary impaction group, the prediction printouts significantly overestimated the total anterior soft tissue facial height, the upper lip height and the inclination and curvature of the lower lip and underestimated the soft tissue thickness in the regions of pogonion and point B.

Short-term consequences of orthognathic surgery on stomatognathic function.

Craniomandibular dysfunction, mandibular range of motion and occlusal contacts subsequent to surgical-orthodontic treatment were studied in 20 adults with Le Fort I impaction and/or advancement, 34 with vertical ramus setback, 12 with sagittal split advancement and 16 with Le Fort I impaction, and/or advancement and bilateral vertical ramus setback. All subjects were examined 1 week before surgery and 6 months post-operatively. The results of the study indicated that 6 months post-operatively: (a) There was a decrease (NS) in dysfunction patients in the maxillary and double-jaw osteotomy groups, and an increase in the mandibular advancement osteotomy sample (P < 0.05). (b) There was a significant decrease in maximal interincisal opening in both mandibular osteotomy groups (P < 0.01) and in laterotrusive movements in the mandibular advancement group (P < 0.05). (c) The number and intensity of occlusal contacts increased significantly in the maxillary and mandibular setback osteotomy groups (P < 0.01 and P < 0.001, respectively).

Comparison of velopharyngeal growth patterns between cleft lip and/or palate patients requiring or not requiring pharyngeal flap surgery.

This investigation compares the patterns of velopharyngeal growth in cleft lip and/or palate patients. Those who had velopharyngeal competence and acceptable speech are compared with those who presented with velopharyngeal incompetence requiring pharyngeal flap surgery or prosthesis later. Lateral cephalograms of 30 cleft palate only (CPO), 35 unilateral cleft lip and palate (UCLP), and 20 bilateral cleft lip and palate (BCLP) children of the Lancaster Cleft Palate Clinic were studied. These records were taken at 6 month intervals during the first 2 postnatal years and annually thereafter up to 6 years of age. Soft tissue landmark points in the velopharyngeal region were digitized. Length and thickness of the soft palate and height and depth of the nasopharynx were measured. Evaluation of the growth curves of these four cephalometric variables indicated only two significant differences between children who later required pharyngeal flap surgery and those who did not. These differences were found in the growth in length of the soft palate of the CPO group and in the growth in depth of the nasopharynx of the BCLP group. Based on the present cephalometric data, it is impossible to predict at an early age those cleft lip and/or palate patients who will later require pharyngeal flaps.

Cephalometric evaluation of pharynx, soft palate, adenoid tissue, tongue, and hyoid bone following the use of a mandibular repositioning appliance in obstructive sleep apnea patients.

The aim of this study was to evaluate the pharynx, soft palate, adenoid tissue, tongue, and hyoid bone when a mandibular repositioning appliance was used for managing patients with obstructive sleep apnea. Lateral cephalograms of 45 adult obstructive sleep apnea patients from the Lancaster Cleft Palate Clinic were taken without the appliance and some days later with the device in the mouth. This device was used during sleep for improving patients' respiration. Twenty-four cephalometric variables were evaluated. When the appliance was in the mouth, significant alterations (P < .001) were observed in the distances: (a) between anterior and posterior pharyngeal walls at the level of the second and third cervical vertebrae, respectively; (b) between the most superior point of the tongue and the maxillary plane; and (c) between the hyoid bone and the mandibular plane, ramus plane, cervical vertebrae tangent, mandibular symphysis, gonion, and third and fourth cervical vertebrae. The results of this study indicate that significant changes in pharyngeal space, hyoid bone, and tongue positions take place in obstructive sleep apnea patients when a mandibular repositioning device is used.

Morphologic and functional implications of the surgical-orthodontic management of mandibular prognathism: a comprehensive review.

The aim of this review is to present the various morphologic and functional implications of the surgical-orthodontic management of mandibular prognathism, thus providing a more complete determination of the efficacy of this modality of treatment. Major conclusions that can be drawn from the bibliography indicate that: (1) After treatment considerable improvement takes place on the soft tissue and dentoskeletal profile, occlusal tooth contacts, and temporomandibular joint function and and pain; (2) Surgical management of mandibular prognathism can be associated with decreased maximum interincisal opening; (3) Although immediately after surgery there is a tendency for the condyles to be distracted downward and anteriorly from their preoperative position, in long-term postsurgery the condyles, on the average, regain their initial position; (4) Compensatory alterations in the pharyngeal, suprahyoid, and infrahyoid muscular regions take place postoperatively; (5) Skeletal changes after mandibular setback to correct mandibular prognathism occur frequently, but their magnitude and patterns exhibit variation and are not necessarily detrimental; and (6) Fulfillment of expectations toward surgical-orthodontic management of mandibular prognathism was reported to be frequent.

Evaluation of maxillary dental arch form in unilateral clefts of lip, alveolus, and palate from one month to four years.

This study evaluated the early changes of maxillary alveolar arches of operated unilateral cleft lip and palate patients. Dental casts were available at four age increments. Triangular flap cheiloplasty was carried out at an early age. Two-stage palatoplasty by vomer flap and soft palate closure took place later. Prior to lip repair, the alveolar arches were classified according to the relationship between greater and lesser segments. Almost a quarter had overlap of the alveolar segments with no contact between the alveolar ridges at the cleft site; some had no overlap with contact of the alveolar segments in the cleft region; almost a quarter had both overlap of the alveolar segments and contact; and almost half had no overlap of the segments and the alveolar ridges were not in contact at the cleft site. After lip repair, the arch relationships were examined and the percentage of patients in each of the four groups indicated a moulding effect of lip repair on the alveolar segments. This moulding effect caused the alveolar segments in most patients to be in contact at the cleft site. Most of these also had segment overlap. All patients were re-examined shortly after palatal repair. The trend for segment overlap and contact continued after palate surgery. However, when all patients were seen at age 4, percentages of patients in each group indicated that previous overlap of segments improved to a more desirable nonoverlapped relationship in approximately half of the patients. The other half continued to demonstrate arch collapse, in excess of what would be considered ideal ridge relationship.