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Ciccarino, Pietro (2015) Microparticelle plasmatiche nei pazienti affetti da glioblastoma: ruolo nello sviluppo delle complicanze tromboemboliche venose e potenziale utilizzo come marcatori di progressione neoplastica. [Tesi di dottorato]

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Abstract (inglese)

Background: The clinical course of patients with glioblastoma is burdened with a poor prognosis. Furthermore, the hypercoagulable state associated with this cancer and the possible thromboembolic complications (VTE) may significantly worsen the prognosis. Moreover, the absence of tumor markers in glioblastoma makes the follow-up of these patients strictly dependent on the neuroimaging examination that might be controversial. Circulating tumor-derived microparticles (MPs), that are present in various types of tumors, associated with prothrombotic activity, were also found in the plasma of patients with glioblastoma.
Objective: To evaluate the first postoperative thromboembolic complications after surgery for brain tumor in a sample of patients. To determine the relationship between circulating microparticles (MPs) and thromboembolism. To assess the relationship between MPs and progression of disease in patients treated for newly diagnosed glioblastoma in order to evaluate the possible use of MPs as markers of disease.
Materials and methods: In 57 patients, without TEV and subjected to neurosurgical intervention for glioblastoma and meningioma, blood levels of D-Dimer before surgery and III and VII days after surgery were assayed. All patients received the same antithrombotic prophylaxis and lower extremities ultrasonography before surgery and seven days after surgery.
We measured baselines levels of MPs and procoagulant activity in a second group of 25 patients treated for newly diagnosed GBM and we compared these data with a group of 75 healthy controls. We assayed MPs 1, 4 and 7 months after surgery, and we examined the possible occurrence of thromboembolic complications and disease progression. All patients underwent adjuvant treatment according to the protocol Stupp within 6 weeks after surgery.
Results: In the first group of patients, VTE complication occurred in 17.5 % of patients without clinical signs or symptoms. The D-dimer level significantly increased in the basal sample, in third and seventh postoperative days in patients who developed VTE compared to those who did not develop VTE.
In the second group of patients, circulating MPs and prothrombotic activity were significantly increased in patients compared to healthy controls. These counts were also significantly higher in patients who developed VTE compared to those who did not have this complication. Similarly, the circulating MPs were higher in patients who went against disease progression compared to stable controls.
Conclusions: In the first post-operative period, the D-Dimer plasmatic levels’ trend can help in the diagnosis of VTE in the absence of clinical signs or symptoms. The increase of circulating MPs correlates with VTE strengthening the hypothesis of a prothrombotic role of these particles. The increase of circulating MPs in patients with progression of the disease seems suggest their possible use as tumoral markers.

Abstract (italiano)

Presupposti dello studio: Il decorso dei pazienti affetti del glioblastoma è gravato da una prognosi infausta. Inoltre, l’alterato assetto coagulativo che si associa a questa neoplasia e le possibili complicanze di natura tromboembolica (TEV) possono peggiorarne sensibilmente la prognosi. L’assenza di makers tumorali nel glioblastoma, inoltre, rende il follow-up dei pazienti strettamente dipendente dagli esami di neuroimaging che talvolta possono risultare di difficile interpretazione. Microparticelle plasmatiche di derivazione neoplastica (MPs), descritte in diversi tipi di neoplasie ed associate ad attività procoagulante, sono state riscontrate nei pazienti affetti da glioblastoma.
Scopo dello studio: Valutare la complicanza tromboembolica nell’immediato post operatorio dopo intervento per neoplasia cerebrale in un campione di pazienti. Determinare la relazione tra complicanze tromboemboliche e MPs circolanti e valutare la correlazione tra MPs e progressione di malattia nei pazienti trattati per glioblastoma di nuova diagnosi per comprendere il possibile utilizzo delle MPs come markers di malattia.
Materiali e metodi: In 57 pazienti, esenti da TEV e sottoposti ad intervento neurochirurgico per glioblastoma o meningioma, sono stati dosati i livelli ematici di D-Dimero preoperatoriamente, in III e in VII giornata postoperatoria. A tutti i pazienti è stata somministrata la medesima profilassi antitrombotica, preoperatoriamente e in VII giornata post operatoria è stato effettuato un EcoDoppler venoso.
In un secondo gruppo di 25 pazienti trattati per GBM di prima diagnosi sono state dosate le MPs circolanti basali e quantificata l’attività coagulativa rispetto ad un gruppo di 75 controlli sani. Sono state dosate le MPs a controlli seriati preoperatoriamente, a 1, 4 e 7 mesi dopo la chirurgia ed esaminata l’eventuale insorgenza di complicanze tromboemboliche e di progressione di malattia. Tutti i pazienti sono stati sottoposti a terapia adiuvante secondo il protocollo Stupp entro 6 settimane dall’intervento.
Risultati: Nel primo gruppo di pazienti la complicanza tromboembolica si è verificata nel 17.5% dei pazienti in assenza di segni o sintomi clinici. Il D-Dimero è risultato significativamente aumentato nel prelievo basale, in III ed in VII giornata nei pazienti che hanno sviluppato TEV rispetto a quelli che non l’hanno sviluppata con un trend in progressivo aumento.
Nel secondo gruppo di pazienti le MPs circolanti e l’attività procoagulante sono risultate significativamente aumentate rispetto ai controlli sani. Tali dosaggi erano significativamente più elevati nei pazienti che hanno sviluppato una TEV rispetto a quelli che non hanno avuto tale complicanza. Allo stesso modo le MPs circolanti erano più elevate nei pazienti che sono andati incontro a progressione di malattia rispetto ai controlli stabili.
Conclusioni: Nell’immediato post operatorio l’andamento del D-Dimero può aiutare nella diagnosi di TEV in assenza di segni o sintomi evidenti. L’aumento delle MPs circolanti correla con la comparsa di TEV rafforzando l’ipotesi del ruolo procoagulante di queste particelle. L’aumento delle MPs nei pazienti con progressione di malattia, inoltre, sembra suggerire il loro possibile utilizzo come markers di malattia.

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Tipo di EPrint:Tesi di dottorato
Relatore:d'Avella, Domenico
Dottorato (corsi e scuole):Ciclo 27 > scuole 27 > SCIENZE MEDICHE, CLINICHE E SPERIMENTALI > NEUROSCIENZE
Data di deposito della tesi:31 Luglio 2015
Anno di Pubblicazione:31 Luglio 2015
Parole chiave (italiano / inglese):Glioblastoma, microparticelle, tromboembolismo venoso, biomarcatori. Glioblastoma, microparticles, venuos tromboembolism, biomarkers,
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/27 Neurochirurgia
Struttura di riferimento:Dipartimenti > Dipartimento di Neuroscienze
Codice ID:8931
Depositato il:25 Ago 2016 12:30
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