Intra-thoracic desmoid tumour in a patient with a previous aortocoronary bypass

BACKGROUND: Intra-thoracic desmoid tumours with mediastinal invasion are very rare. Although rare they have to be taken into account in the differential diagnosis of a thoracic mass and therapeutic options have to be weighted since surgical treatment may require wide excision. CASE PRESENTATION: A 48-year-old male diabetic, dyslipidaemic, former heavy smoker with psychiatric illness was operated by sternotomy for a triple aorto-coronary bypass 4 years before, presented with complains of recent onset such as constant and oppressive chest pain. At surgery a mass extending from the aortic arch into the entire anterior mediastinum and to most of the right pleural cavity was found. The mass was separated from sternal periosteum and vessels of aorto-coronary by pass were isolated starting from the aortic arch up to the pericardium. The histological examination revealed aggressive fibromatosis. CONCLUSION: Although technically demanding, radical surgical excision is actually the most indicated therapeutic approach for intra-thoracic desmoid tumours

Malattia di Paget perianale: presentazione di 5 casi

Obiettivo. La malattia di Paget extramammaria (EMPD) è una neoplasia molto rara che frequentemente si associa a carcinomi cutanei o viscerali, sincroni o metacroni. Obiettivo dello studio è valutare retrospettivamente i risultati ottenuti in 5 casi di malattia di Paget perianale osservati e rivedere la letteratura sull’argomento. Pazienti e metodi. Cinque pazienti con EMPD perianale sono stati trattati presso la nostra Divisione da marzo 1996 a dicembre 2006. In 3 casi la malattia era confinata entro l’epidermide, in un caso plurirecidivo era presente un’infiltrazione del derma e un paziente presentava un adenocarcinoma del retto inferiore con diffusione pagetoide. I pazienti sono stati sottoposti ad ampie exeresi perianali e ricostruzioni con graft cutanei. L’asportazione dell’adenocarcinoma del retto è stata realizzata per via transanale. In due casi è stata eseguita una sigmoidostomia di protezione per favorire la guarigione della ferita. Risultati. Non si sono verificate complicanze postoperatorie, neanche a distanza. In due casi la malattia ha recidivato localmente, ma nessun paziente ha presentato metastasi a distanza. Quattro pazienti sono vivi e liberi da malattia, mentre un paziente con recidiva di malattia è deceduto per insufficienza cardiocircolatoria. Discussione. L’analisi della letteratura consente un’identificazione chiara della EMPD primitiva (intraepiteliale/intradermica) e della forma associata ad adenocarcinomi anorettali, interpretata come diffusione pagetoide. Poche informazioni sono invece ricavabili nei casi in cui la malattia si presenta come adenocarcinoma degli annessi. La malattia tende a recidivare anche dopo chirurgia exeretica radicale e ha capacità metastatizzanti, anche nella forma in situ. Conclusioni. La malattia di Paget perianale è una patologia complessa e difficile da diagnosticare. L’ associazione con carcinomi sincroni o metacroni impone follow-up lunghi con controlli clinici e strumentali frequenti

One for All, All for One: The Peculiar Dynamics of TNF-Receptor-Associated Factor (TRAF2) Subunits

TNF Receptor-Associated Factor 2 (TRAF2) is a homo-trimer belonging to the TNF-receptor-associated factor family (TRAFs). The TRAF2 oligomeric state is crucial for receptor binding, the interaction with other proteins (involved in the TNFR signaling), and the interaction with biological membranes. In this study, we present a computational analysis of the Molecular Dynamics of TRAF2-C (a truncated and soluble TRAF2 form) to identify patterns in the interactions between the three chains. We have performed a canonical analysis of the motion applied to molecular dynamics starting from the available crystal structure to identify correlated motions in TRAF2 dynamics. We have computed the displacement matrix, providing a frame-by-frame displacement for each residue in the dynamic. We provide the results in terms of the correlation matrix, which represents a detailed map of the correlated motions of residues. Eventually, we computed the so-called dynamical clusters, based on the Principal Component Analysis (PCA) of the motion (displacement) and the k means application on the first two principal components space. The results clearly indicate that, most of the time, two chains move in a strongly correlated motion, while the third chain follows a freer motion. A detailed analysis of the correlation matrix also shows that a few specific interface residues characterize the interaction of the more independent subunit with the other two. These findings suggest that the equilibrium between the trimer and the dissociated species (dimers and monomers) might be finely tuned by controlling a few critical residues in the protein quaternary structure, probably facilitating the regulation of oligomerization and dissociation in vivo

One for All, All for One: The Peculiar Dynamics of TNF-Receptor-Associated Factor (TRAF2) Subunits

TNF Receptor-Associated Factor 2 (TRAF2) is a homo-trimer belonging to the TNF-receptor-associated factor family (TRAFs). The TRAF2 oligomeric state is crucial for receptor binding, the interaction with other proteins (involved in the TNFR signaling), and the interaction with biological membranes. In this study, we present a computational analysis of the Molecular Dynamics of TRAF2-C (a truncated and soluble TRAF2 form) to identify patterns in the interactions between the three chains. We have performed a canonical analysis of the motion applied to molecular dynamics starting from the available crystal structure to identify correlated motions in TRAF2 dynamics. We have computed the displacement matrix, providing a frame-by-frame displacement for each residue in the dynamic. We provide the results in terms of the correlation matrix, which represents a detailed map of the correlated motions of residues. Eventually, we computed the so-called dynamical clusters, based on the Principal Component Analysis (PCA) of the motion (displacement) and the k means application on the first two principal components space. The results clearly indicate that, most of the time, two chains move in a strongly correlated motion, while the third chain follows a freer motion. A detailed analysis of the correlation matrix also shows that a few specific interface residues characterize the interaction of the more independent subunit with the other two. These findings suggest that the equilibrium between the trimer and the dissociated species (dimers and monomers) might be finely tuned by controlling a few critical residues in the protein quaternary structure, probably facilitating the regulation of oligomerization and dissociation in vivo

Diverticulostomia endoscopica per diverticolo di Zenker. Esperienza su 123 casi

Scopo. L’intento di questo studio era quello di valutare i risultati a breve termine in pazienti con diverticolo di Zenker sottoposti a esofago-diverticulostomia endoscopica secondo Collard. Pazienti e metodi. L’analisi retrospettiva è stata realizzata in 123 pazienti. Il sintomo più comune era rappresentato dalla disfagia, severa in 50 casi (40,6%) e moderata nei restanti 73 (59,4%), con un “dysphagia score” medio di 2,3 (range 0-4). Il rigurgito era presente in 70 casi (56,9%) con uno score medio di 0,8 (range 0-2). Il diametro medio del diverticolo era di 4,1 cm (range 2,5-10). La procedura endoscopica è stata eseguita in 87 maschi e 36 femmine con un follow-up medio di 69,1 mesi (range 1-168). Risultati. Sono stati buoni in 82 casi (66,7%) e discreti in 24 (19,5%), dati confermati anche dalle variazioni del “dysphagia score” pre- vs post-operatorio (2,3 vs 0,4) e dello score per il rigurgito (0,8 vs 0,2). Gli insuccessi sono stati 17 (13,8%). La durata media dell’intervento è stata di 18 minuti (range 15-40), quella del ricovero di 2,5 giorni (range 1-5) con ripresa dell’alimentazione in genere in I giornata post-operatoria. Le complicanze maggiori si sono avute in 2 casi (1,6%), mentre minori in 10 casi (8,1%), con una mortalità nulla. Conclusioni. L’esofago-diverticulostomia endoscopica secondo Collard, in base alla nostra esperienza e ai dati della letteratura, rappresenta attualmente la tecnica più vantaggiosa e sicura per i pazienti affetti da diverticolo di Zenker, con minori percentuali di morbilità e mortalità rispetto ad altre tecniche chirurgiche o endoscopich

Telomere shortening and PCDH10 promoter methylation in colorectal cancer mucosae

Background: telomerase activity and telomere length (TL) have important implications in several human diseases.Telomere shortening is associated with colorectal carcinogenesis. Recent studies also showed that protocadherin 10(PCDH10) plays a critical role in cancer cell growth, by negatively regulating telomerase activity. PCDH10isfrequently downregulated by promoter DNA methylation. The aim of this study was to investigate whether PCDH10promoter methylation was associated with TL in colorectal cancer (CRC). Methods: DNA was extracted from 35 CRC and 35 adjacent normal tissues with Gentra Purgene Kit (Qiagen, Hilden,Germany). A quantitative methylation-specific PCR (MSP) based method was used to analyze a selected CpG site inPCDH10promoter. TL was evaluated with qPCR and expressed as telomere to single copy gene (T/S) ratio.Differences were assessed with Mann-Whitney test or Wilcoxon signed-ranks test when appropriate, whilstcorrelation analyses were performed with Spearman\u2019s test. Diagnostic performance was calculated with receiveroperating characteristics (ROC) curve analysis. The level of statistical significance was set at p <0.05. Results: we found that TL was significantly lower in CRC than in adjacent non-cancerous tissues (p=0.0005). Thearea under the ROC curve (AUC) for TL was 0.759 (95% Confidence Interval: 0.643-0.875, p=0.0002). AberrantPCDH10promoter methylation was detected in 100% of CRC tissues but in none of paired non-cancerous tissues.The median methylation rate in CRC tissues was 55.7% (range: 6.1-97.8%). TL was negatively correlated withPCDH10promoter methylation (r=-0.42, p=0.0002). Conclusions: these results suggest a pivotal role of telomere shortening and PCDH10methylation in CRC tissues.TL may be seen as a potential biomarker in CRC diagnostics

Survival of patients with skin melanoma in Europe increases further: Results of the EUROCARE-5 study

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageBackground: In Europe skin melanoma (SM) survival has increased over time. The aims were to evaluate recent trends and differences between countries and regions of Europe. Methods: Relative survival (RS) estimates and geographical comparisons were based on 241,485 patients aged 15 years and over with a diagnosis of invasive SM in Europe (2000-2007). Survival time trends during 1999-2007 were estimated using the period approach, for 213,101 patients. Age, gender, sub-sites and morphology subgroups were considered. Results: In European patients, estimated 5-year RS was 83% (95% confidence interval, CI 83-84%). The highest values were found for patients resident in Northern (88%; 87-88%) and Central (88%; 87-88%) Europe, followed by Ireland and United Kingdom (UK) (86%; 85-86%) and Southern Europe (83%; 82-83%). The lowest survival was in Eastern Europe (74%; 74-75%). Within regions the intercountry absolute difference in percentage points of RS varied from 4% (North) to 34% (East). RS decreased markedly with patients' age and was higher in women than men. Differences according to SM morphology and skin sub-sites also emerged. Survival has slightly increased from 1999 to 2007, with a small improvement in Northern and the most pronounced improvement in Eastern Europe. Discussion: SM survival is high and still increasing in European patients. The gap between Northern and Southern and especially Eastern European countries, although still present, diminished over time. Differences in stage distribution at diagnosis may explain most of the geographical differences. However, part of the improvement in survival may be attributed to overdiagnosis from early diagnosis practice

Plasma expression levels of circulating miR-21 are not useful for diagnosing and monitoring colorectal cancer

BACKGROUND: Recent evidence suggests that microRNAs play an important role in cancer diagnostics. We assessed plasma microRNA-21 levels in patients with colorectal cancer (CRC) at different stages and in patients with benign polyps.METHODS: Plasma levels of miR-21 were assessed by quantitative reverse transcription polymerase chain reaction assay in plasma samples of 76 CRC patients and in 20 patients with benign polyps. Differences between groups were evaluated with Mann-Whitney and Kruskal-Wallis tests.RESULTS: No significant differences of miR-21 plasma levels were observed between CRC patients and subjects with benign polyps (p > 0.05). Also, no significant differences were found between CRC patients with advanced (III-IV) or early cancer stages (I-II) (p > 0.05).CONCLUSIONS: These results do not support the hypothesis that circulating miR-21 expression is increased in adenoma-carcinoma-advanced carcinoma sequence. Accordingly, plasma miR-21 assessment does not appear to be a useful biomarker for diagnosing and staging CRC

Comparison of genetic and epigenetic alterations of primary tumors and matched plasma samples in patients with colorectal cancer.

Although recent advances in circulating DNA analysis allow the prediction of tumor genomes by noninvasive means, some challenges remain, which limit the widespread introduction of cfDNA in cancer diagnostics. We analyzed the status of the two best characterized colorectal cancer (CRC) genetic and epigenetic alterations in a cohort of CRC patients, and then compared the degree to which the two patterns move from tissue to plasma in order to improve our understanding of biology modulating the concordance between tissues and plasma methylation and mutation profiles.Plasma and tumor tissues were collected from 85 patients (69±14 years, 56 males). KRAS and SEPT9 status was assessed by allele refractory mutation system quantitative PCR and quantitative methylation-specific PCR, respectively. Six of the most common point mutations at codon 12 and 13 were investigated for KRAS analysis.KRAS mutations and SEPT9 promoter methylation were present in 34% (29/85) and in 82% (70/85) of primary tumor tissue samples. Both genetic and epigenetic analyses of cfDNA revealed a high overall concordance and specificity compared with tumor-tissue analyses. Patients presenting with both genetic and epigenetic alterations in tissue specimens (31.8%, 27/85) were considered for further analyses. The median methylation rates in tumour tissues and plasma samples were 64.5% (12.2-99.8%) and 14.5% (0-45.5%), respectively. The median KRAS mutation load (for matched mutations) was 33.6% (1.8-86.3%) in tissues and 2.9% (0-17.3) in plasma samples. The plasma/tissue (p/t) ratio of SEPT9 methylation rate was significantly higher than the p/t ratio of KRAS mutation load, especially in early stage cancers (p=0.0108).The results of this study show a discrepant rate of epigenetic vs. genetic alterations moving from tissue to plasma. Many factors could affect mutation cfDNA analysis, including both presence of tumor clonal heterogeneity and strict compartmentalization of KRAS mutation profile. The present study highlights the importance of considering the nature of the alteration when analyzing tumor-derived cfDNA