Thèses sur le sujet « Local ablation »

Lorsqu'une impulsion laser est focalisée sur une cible solide immergée dans un liquide, de la matière est vaporisée. La nucléation et la croissance ont lieu dans le liquide et des nanoparticules sont ainsi synthétisées. La méthode est très polyvalente puisqu'une grande variété de matériaux peut être générée. De plus, les nanoparticules sont directement stabilisées dans le solvant. L'ajout d'agent complexant n'est pas nécessaire mais peut tout de même permettre de mieux contrôler la taille des nanoparticules. Cependant, de nombreux processus sont mis en jeu durant la synthèse et l'objectif de ce travail doctoral est de développer la compréhension de ces éléments. Dans la mesure où l'ablation laser déploie une multitude d'´échelle de temps, il a fallu employer différentes méthodes pour élucider ces mécanismes. Pour commencer, je définirai un état de l'art de l'utilisation de l'ablation laser en milieu liquide et nos résultats concernant la synthèse d'aluminium oxyde dopé chrome. Par la suite, je présenterai la spectroscopie des plasmas et les questions sous-jacentes à la notion d'´équilibre dans un plasma moléculaire. Ensuite, je décrirai notre approche atomistique de la nucléation basée sur les techniques de chimie quantique. Enfin, je montrerai l'apport de l'utilisation des méthodes d'ombrographie pour mieux comprendre la thermodynamique du système au temps plus long. Notre étude démontre que la bulle formée suite à l'ablation laser est constituée essentiellement de molécule du solvant dont la quantité n'évolue quasiment pas au cours du temps de vie de la bulle
When a pulsed-laser is focused into a solid target immersed in water, the material is evaporated. Nucleation and growth occur in the liquid and nanoparticles are synthesized. The method can be considered as versatile because one can try to synthesize any kinds of materials. Also, the nanoparticles are directly stabilized by the solvant so there is no need of complexing agents. The nanoparticles are described as ligand-free. However, various processes can occur during the synthesis and the aim of my work is to understand these different components. Since the laser ablation in liquid displays a wide range of timescales, we used numerous methods to address this problem. First, I will present the use of plasma spectroscopy and the questions it raises towards local thermodynamic equilibrium. Then, I will describe our microscopic approach of nucleation based on quantum chemistry techniques. Finally, I will illustrate the advantages of shadowgraphic measurements to reach an hydrodynamic understanding of the system

Local tumour progression remains the main problem after radiofrequency ablation of liver tumours and it is usually the only measure of treatment efficacy. The aim of our study was to investigate and evaluate the prognostic value of computed tomography and ultrasonography as well as the histological result of core biopsy material from ablated tumour on assessment of radiofrequency ablation effectiveness. Materials and methods: We have studied 68 malignant primary and metastatic hepatic tumours treated by radiofrequency ablation. Ablation was performed using perfusion electrodes. Evaluation of tumours before ablation and follow up was performed by means of contrast enhanced computed tomography and ultrasonography. Ablation zone was biopsied for histological examination. Results and conclusions: 58 successfully treated hepatic tumours were suitable for the final analysis. The local progression of nine (15.5 %) tumours was detected on follow up. Mean follow up time for analysed tumours was 16.3 months with a range from 1.7 to 38.7 months. It was showed, that: 1. The result of histological examination of ablation zone biopsy material taken one month after radiofrequency ablation of malignant liver tumour does not predict local tumour progression. 2. Tumour size 30 mm and larger and tumour proximity closer than 5 mm to hepatic vessels larger than 3 mm are significant risk factors for local tumour progression after radiofrequency ablation of malignant liver tumours 3. Tumour type... [to full text]
Nors vietinis naviko progresavimas yra esminė problema, atliekant piktybinių navikų kepenyse radijo dažnio abliaciją, dažniausiai tai yra vienintelis rodiklis, apibrėžiantis šio gydymo metodo veiksmingumą. Mūsų tyrimo tikslas buvo nustatyti kompiuterinės tomografijos ir ultragarso tyrimų bei histologinio stulpelinės biopsijos medžiagos, paimtos iš abliuoto naviko, histologinio tyrimo rezultato reikšmę anksti vertinant radijo dažnio abliacijos veiksmingumą. Tyrimo medžiaga ir metodai: Į tyrimą buvo įtraukti 68 pirminiai ir metastaziniai kepenyse esantys navikai. Radijo dažnio abliacija buvo atliekama naudojant perfuzijos elektrodus. Navikai prieš abliaciją ir po jos atliekant kontrolinius tyrimus buvo vertinami kompiuterinės tomografijos ir ultragarsinio tyrimo metodais. Po abliacijos praėjus vienam mėnesiui buvo atliekama abliacijos zonos punkcinė stulpelinė biopsija, audiniai tiriami histologiškai. Rezultatai ir išvados: Galutinei analizei buvo tinkami 58 sėkmingai gydyti navikai. Radiologinio stebėjimo metu buvo nustatyti devyni (15,5 %) vietinio naviko progresavimo atvejai. Vidutinis analizuotų navikų stebėjimo laikas buvo 16,3 mėnesiai (nuo 1,7 iki 38,7 mėnesių). Nustatyta, kad: 1. Biopsijos medžiagos, paimtos iš abliacijos zonos praėjus vienam mėnesiui po naviko, esančio kepenyse, radijo dažnio abliacijos, histologinio tyrimo rezultatas neleidžia prognozuoti vietinio naviko progresavimo 2. Naviko dydis 30 mm ir naviko lokalizacija arčiau kaip per 5 mm nuo didesnio nei 3... [toliau žr. visą tekstą]

Nanodiamonds (NDs) are the subject of intense investigation for their unique physical and chemical properties. Due to high hardness, optical transparency and biocompatibility, NDs find applications in tribology, catalysis and drug delivery. When enriched with nitrogen-vacancy (NV) centers, NDs can be used in bioimaging and biosensing. While the field is progressing rapidly, a number of problems are still open. In this dissertation I have tackled two important aspects for the development of NDs as biosensors: 1) production of NDs with controlled size and properties; 2) characterization and optimization of commercial fluorescent NDs as probes of paramagnetic species. In the first part of my thesis, I report a novel synthesis route for NDs by pulsed laser ablation (PLA) in water. PLA can directly produce diamonds on a nanoscopic scale, with potential advantages over alternative methods, like grinding of bulk crystals or detonation techniques. Specifically, I demonstrate synthesis of nanometric diamond crystals by PLA in an aqueous environment and investigate the thermodynamics of this process. Indeed, the synthesis of NDs by PLA is related to a drastic change in the thermodynamic state of the target upon laser irradiation. Fast laser-induced heating results in melting and superheating of the target, followed by a strong boiling, a process named “phase explosion†, and then by a fast cooling of the molten material in water. I provide a theoretical description of both superheated and undercooled liquids and of the mechanism of phase explosion. The investigation of the link between the metastable liquids (superheated or undercooled) and the synthesis of nanoparticles is carried out by theoretical analyses, computer simulations and comparison of our experimental data with previous literature. In the second part of the thesis I turn to commercial NDs enriched with (NV) centers. The purpose of the investigation is to explore the use of fluorescent NDs for sensing of paramagnetic species of biological interest. To this end, I explored the effects of size and surface coating on the optical properties and sensing capabilities of fluorescent NDs. Following a theoretical introduction to the basic properties of the NV centers and to the ground state spin dynamics of these color centers, I describe the set up used for the experimental characterization of the NDs. All NDs used in my experiments, characterized by different sizes and coatings, presented high fluorescence levels, the result of a relatively high concentration of NV center. In all NDs, I observed a fast loss in coherence due to interactions between the NV centers and with the external environment. The most striking and unexpected result concerns the dynamics of the spin-lattice relaxation time T1. Differently from previous reports, spin dynamics after polarization of NV centers could not be described by a single exponential decay, but showed a sharp signal increase that I attribute to charge dynamics and charge conversion between the negative and neutral forms of the NV center. Unexpectedly, I found that coupled charge and spin dynamics are strongly affected by paramagnetic interactions, yielding unprecedented sensitivity to subnanomolar concentrations of gadolinium, a strong paramagnetic contrast agent. The connection between relaxation dynamics and concentration of paramagnetic species can open new perspectives in biosensing and in bioimaging. As a demonstration of a practical application, I tested the sensitivity of NDs in the detection of deoxyhemoglobin, an endogenous paramagnetic species in blood.

La destruction locale de tumeurs sous contrôle IRM offre une nouvelle altérnative aux traite-ments classiques du cancer comme la chirurgie, la radio- et la chimio-thérapie. Parmi toutes les modalités d'induction d'une hyperthermie locale, seuls les ultrasons focalisés (USF) per-mettent une approche non-invasive. Le contrôle IRM de l'hyperthermie locale nécessite une cartographie de température rapide et fiable. La méthode basée sur la fréquence de résonance de protons de l'eau est préférée en raison de sa linéarité et de son indépendance par rapport à la nature du tissu. Les modifications locales dans la susceptibilité magnétique, ainsi que les mouvements du tissu, peuvent engendrer des erreurs dans les cartes de température obtenues par cette méthode. Des techniques de correction temps-réel sont donc demandées. La cartogra-phie rapide de température par IRM permet le contrôle temps-réel de la température au point focal. Le traitement de volumes grands par rapport à la zone focale peut être accompli par un déplacement du point focal le long d'une trajectoire optimisée, alors que le faisceau USF est émis en mode continu. Cette méthode conduit à une destruction uniforme et contigue du volume tumoral et réduit considérablement la durée du traitement, conformément aux résultats obtenus sur le carcinome VX2 implanté chez le lapin. La technologie des émetteurs en réseau phasé devrait améliorer les performances de cette méthode de chauffage. Les premiers essais cliniques chez l'homme concerneront probablement le traitement de tumeurs du sein.

Vitamin D is very well known for its classical role in the maintenance of calcium and phosphorus homeostasis as well as in the prevention of rickets. More recent findings of its ability to inhibit cell proliferation, induce apoptosis, induce differentiation, inhibit angiogenesis, and modulate the immune system have made it a current topic of intense research, particularly in the field of cancer research. We used a murine model of breast cancer metastasis to bone to investigate the effect of vitamin D deficiency on the growth of breast cancer tumour cells within bone. We also established that these breast cancer tumour cells express the enzyme CYP27B1 (1α-hydroxylase) which is able to convert the inactive vitamin D precursor 25-hydroxyvitamin D (25(OH)D) to the active metabolite 1,25-dihydroxyvitamin D (1,25(OH)2D). We next examined the effect of the local activation of vitamin D by tumoral CYP27B1 on the growth of these tumour cells within bone. Although we did not see a significant difference in the growth of breast cancer tumour cells in the bones of vitamin D deficient mice as compared to vitamin D sufficient mice, we have demonstrated that breast cancer tumour cells that do not express CYP27B1 grow much more aggressively within bone than breast cancer tumour cells which express CYP27B1. This suggests a very important role for the local activation of vitamin D by extra-renal CYP27B1 on the growth of breast cancer tumour cells within the bone microenvironment. These findings suggest a potential use for 25(OH)D as a treatment for breast cancer metastasis to bone either alone or in combination.
La vitamine D est bien connue pour son rôle dans le maintien des concentrations de calcium et du phosphore dans la circulation ainsi que dans la prévention du rachitisme. La découverte plus récente de sa capacité d'inhiber la prolifération cellulaire, induire leur différentiation ainsi que l'apoptose cellulaire, inhiber l'angiogenèse, et moduler le système immunitaire rend son étude un sujet de recherche très intéressant surtout dans le domaine de la recherche sur le cancer. Nous avons étudié l'effet de la carence en vitamine D sur la croissance tumorale dans un modèle murin de métastases osseuses du cancer du sein. Nous avons aussi établi que ces cellules expriment l'enzyme CYP27B1 (1α-hydroxylase) et sont donc capables d'activer la vitamine D en son métabolite actif la 1,25-dihydroxyvitamine D (1,25(OH)2D) à partir du métabolite inactif, la 25-hydroxyvitamine D (25(OH)D). Nous avons ensuite examiné l'effet de l'activation locale de la vitamine D par les cellules tumorales dérivées du sein sur la croissance de ces cellules dans le microenvironnement osseux. Nous n'avons constaté aucune différence significative entre la croissance des cellules tumorales du cancer du sein dans l'os chez les souris carencées en vitamine D en comparaison aux souris non carencées en vitamine D. Cependant, nous avons démontré que les cellules tumorales du cancer du sein qui expriment le CYP27B1 croissent beaucoup moins vite dans l'os que les cellules tumorales qui n'expriment pas le CYP27B1. Ces résultats suggèrent un rôle très important de l'activation extra-rénale de la vitamine D par les cellules tumorales du cancer du sein pour inhiber la croissance de ces cellules dans l'os. En conclusion, ces travaux indiquent que le précurseur inactif 25(OH)D pourrait être utilisé seul ou en combinaison pour le traitement des métastases osseuses du cancer du sein.

Nors vietinis naviko progresavimas yra esminė problema, atliekant piktybinių navikų kepenyse radijo dažnio abliaciją, dažniausiai tai yra vienintelis rodiklis, apibrėžiantis šio gydymo metodo veiksmingumą. Mūsų tyrimo tikslas buvo nustatyti kompiuterinės tomografijos ir ultragarso tyrimų bei histologinio stulpelinės biopsijos medžiagos, paimtos iš abliuoto naviko, histologinio tyrimo rezultato reikšmę anksti vertinant radijo dažnio abliacijos veiksmingumą. Tyrimo medžiaga ir metodai: Į tyrimą buvo įtraukti 68 pirminiai ir metastaziniai kepenyse esantys navikai. Radijo dažnio abliacija buvo atliekama naudojant perfuzijos elektrodus. Navikai prieš abliaciją ir po jos atliekant kontrolinius tyrimus buvo vertinami kompiuterinės tomografijos ir ultragarsinio tyrimo metodais. Po abliacijos praėjus vienam mėnesiui buvo atliekama abliacijos zonos punkcinė stulpelinė biopsija, audiniai tiriami histologiškai. Rezultatai ir išvados: Galutinei analizei buvo tinkami 58 sėkmingai gydyti navikai. Radiologinio stebėjimo metu buvo nustatyti devyni (15,5 %) vietinio naviko progresavimo atvejai. Vidutinis analizuotų navikų stebėjimo laikas buvo 16,3 mėnesiai (nuo 1,7 iki 38,7 mėnesių). Nustatyta, kad: 1. Biopsijos medžiagos, paimtos iš abliacijos zonos praėjus vienam mėnesiui po naviko, esančio kepenyse, radijo dažnio abliacijos, histologinio tyrimo rezultatas neleidžia prognozuoti vietinio naviko progresavimo 2. Naviko dydis 30 mm ir naviko lokalizacija arčiau kaip per 5 mm nuo didesnio nei 3... [toliau žr. visą tekstą]
Local tumour progression remains the main problem after radiofrequency ablation of liver tumours and it is usually the only measure of treatment efficacy. The aim of our study was to investigate and evaluate the prognostic value of computed tomography and ultrasonography as well as the histological result of core biopsy material from ablated tumour on assessment of radiofrequency ablation effectiveness. Materials and methods: We have studied 68 malignant primary and metastatic hepatic tumours treated by radiofrequency ablation. Ablation was performed using perfusion electrodes. Evaluation of tumours before ablation and follow up was performed by means of contrast enhanced computed tomography and ultrasonography. Ablation zone was biopsied for histological examination. Results and conclusions: 58 successfully treated hepatic tumours were suitable for the final analysis. The local progression of nine (15.5 %) tumours was detected on follow up. Mean follow up time for analysed tumours was 16.3 months with a range from 1.7 to 38.7 months. It was showed, that: 1. The result of histological examination of ablation zone biopsy material taken one month after radiofrequency ablation of malignant liver tumour does not predict local tumour progression. 2. Tumour size 30 mm and larger and tumour proximity closer than 5 mm to hepatic vessels larger than 3 mm are significant risk factors for local tumour progression after radiofrequency ablation of malignant liver tumours 3. Tumour type... [to full text]

Les arythmies sont des perturbations du rythme cardiaque qui peuvent entrainer la mort subite et requièrent une meilleure compréhension pour planifier leur traitement. Dans cette thèse, nous intégrons des données structurelles et fonctionnelles à un maillage 3D tétraédrique biventriculaire. Le modèle biophysique simplifié de Mitchell-Schaeffer (MS) est utilisé pour étudier l’hétérogénéité des propriétés électrophysiologiques (EP) du tissu et leur rôle sur l’arythmogénèse. L’ablation par radiofréquence (ARF) en éliminant les activités ventriculaires anormales locales (LAVA) est un traitement potentiellement curatif pour la tachycardie ventriculaire, mais les études EP requises pour localiser les LAVA sont longues et invasives. Les LAVA se trouvent autour de cicatrices hétérogènes qui peuvent être imagées de façon non-invasive par IRM à rehaussement tardif. Nous utilisons des caractéristiques d’image dans un contexte d’apprentissage automatique avec des forêts aléatoires pour identifier des aires de tissu qui induisent des LAVA. Nous détaillons les sources d’erreur inhérentes aux données et leur intégration dans le processus d’apprentissage. Finalement, nous couplons le modèle MS avec des géométries du coeur spécifiques aux patients et nous modélisons le cathéter avec une approche par un dipôle pour générer des électrogrammes normaux et des LAVA aux endroits où ils ont été localisés en clinique. Cela améliore la prédiction de localisation du tissu induisant des LAVA obtenue par apprentissage sur l’image. Des cartes de confiance sont générées et peuvent être utilisées avant une ARF pour guider l’intervention. Les contributions de cette thèse ont conduit à des résultats et des preuves de concepts prometteurs
Cardiac arrhythmias are heart rhythm disruptions which can lead to sudden cardiac death. They require a deeper understanding for appropriate treatment planning. In this thesis, we integrate personalized structural and functional data into a 3D tetrahedral mesh of the biventricular myocardium. Next, the Mitchell-Schaeffer (MS) simplified biophysical model is used to study the spatial heterogeneity of electrophysiological (EP) tissue properties and their role in arrhythmogenesis. Radiofrequency ablation (RFA) with the elimination of local abnormal ventricular activities (LAVA) has recently arisen as a potentially curative treatment for ventricular tachycardia but the EP studies required to locate LAVA are lengthy and invasive. LAVA are commonly found within the heterogeneous scar, which can be imaged non-invasively with 3D delayed enhanced magnetic resonance imaging (DE-MRI). We evaluate the use of advanced image features in a random forest machine learning framework to identify areas of LAVA-inducing tissue. Furthermore, we detail the dataset’s inherent error sources and their formal integration in the training process. Finally, we construct MRI-based structural patient-specific heart models and couple them with the MS model. We model a recording catheter using a dipole approach and generate distinct normal and LAVA-like electrograms at locations where they have been found in clinics. This enriches our predictions of the locations of LAVA-inducing tissue obtained through image-based learning. Confidence maps can be generated and analyzed prior to RFA to guide the intervention. These contributions have led to promising results and proofs of concepts

L’ablazione laser percutanea (PLA) è stata proposta come trattamento efficace nell’ottenere un’ablazione completa di piccoli epatocarcinoma (<4cm). Tuttavia, non ci sono dati riguardo l’efficacia della PLA nel trattamento di lesioni cosiddette ad “alto rischio”. Obiettivo. Valutare se le cosiddette lesioni a rischio (vicine a strutture vitali) hanno un impatto sulla probabilità di ablazione completa, di recidiva locale e di sopravvivenza complessiva in pazienti con piccolo HCC trattato con PLA ecoguidata Materiali e Metodi. 182 piccoli HCC in 164 pazienti cirrotici sono stati trattati con PLA sotto guida ecografica tra il 1996 ed il 2008. Centosei pazienti (52M/54F; età media 69 anni) avevano 116 HCC (diametro medio 2.7 cm ; range 0.8- 4.0 cm ), sia con crescita esofitica o situati a meno di 1cm dalla capsula epatica o da strutture vitali (Gruppo ad alto rischio). Cinquantotto pazienti (38M/20F, età 68anni) avevano 66 HCC (diametro medio 2.4 cm ; range 0.8- 4.8 cm ) situati in sedi non ad alto rischio (gruppo a basso rischio). Curve di sopravvivenza sono state calcolate mediante lo stimatore di Kaplan-Meier e confrontate mediante il Log-Rank test. L’analisi multivariata è stata condotta mediante il modello di Cox. Risultati. L’ablazione completa iniziale non ha mlostrato differnze significative nei due gruppi ( 96.5 % vs 92.4%) (p= .497). La mediana di follow-up complessivoè stata di 81 mesi. Per I pazienti che hanno ottenuto un’ablazione completa, il tempo mediano di recidiva locale stimato è stato di 84 mesi nel gruppo ad alto rischio e di 134 in quello a basso rischio. La sede non ha mostrato un effetto significativo sulla probabilità di recidiva locale (p= .53) sia all’aalisi univariata che multivariata. L’analisi secondo il modello di Cox ha mostrato che il diametro massimo della lesione è l’unico fattore predittivo di recidiva locale (p= .01). la sopravvivenza complessiva non differisce in maniera significativa tra i due gruppi (p= .374) e la sopravvivenza a 1, 3- e 5-anni è stata dello 0.90 (s.e.=0.029), 0.54 (s.e.=0.053) e 0.33 (s.e.=0.054) nel gruppo ad alto rischio e dello 0.95 (s.e.=0.030), 0.66 (s.e.=0.070) e 0.33 (s.e.=0.074) nel gruppo a basso rischio. All’analisi multivariata la sede non ha mostrato un impatto sulla sopravvivenza statisticamente significativo. Conclusioni. La sede ad alto rischio di piccolo epatocarcinomi trattati con PLA sotto guida ecografica non influenza in maniera significativa la sopravvivenza ed il tempo di recidiva locale di questi pazienti.
Background. Percutaneous laser ablation (PLA) has been proposed as an active treatment in patients with hepatocellular carcinoma with a significant activity in inducing complete ablation in HCC <4cm,. However, to date no data reported using PLA in treating lesions at high-risk located. Aim. To evaluate if the so-called high-risk location (e.g. close to vital structures) affects initial complete ablation rate, local recurrence rate and overall survival in cirrhotic patients with small hepatocellular carcinoma (HCC) treated with US-guided percutaneous laser ablation (LA) Materials and Methods. 182 small HCC nodules in 164 cirrhotic patients were treated by US-guided PLA (USg-PLA) between 1996 and 2008. One hundred six patients (52M/54F; mean age 69 yrs) had 116 HCC nodules (mean diameter 2.7 cm ; range 0.8- 4.0 cm ), either with exophytic growth or located <1cm from the liver edge or vital structures (high-risk group). Fifty eight patients (38M/20F, age 68yrs) had 66 HCC tumors (mean diameter 2.4 cm ; range 0.8- 4.8 cm ) located in not high-risk sites (low-risk group). Survival curves obtained via the Kaplan-Meier method were compared using the Log-Rank test. Multivariate analysis was based on Cox model. Results. The initial complete ablation did not significantly differ between the two groups ( 96.5 % vs 92.4%) (p= .497). The overall median follow-up was 81 months. For patients who achieved a complete response, the estimated local recurrence median time was 84 months in the low-risk group and 132 months in the high-risk group. Location did not significantly affect local recurrence free survival (p= .53) at both univariate and multivariate analysys after adjusting for diameter and tumour histology. Results by Cox model suggest the maximum diameter as the only significant predictor of local recurrence (p= .01). The overall survival did not differ significantly between the two groups (p= .374) and the 1-, 3- and 5-yr survival probability was 0.90 (s.e.=0.029), 0.54 (s.e.=0.053) and 0.33 (s.e.=0.054) in the high-risk group and 0.95 (s.e.=0.030), 0.66 (s.e.=0.070) and 0.33 (s.e.=0.074) in the low-risk one. At multivariate analysis location turned out not to be a significant predictor of overall survival. Conclusion. High-risk location of small HCC nodules treated with USg-PLA seems not to affect complete tumor ablation rate, local tumour recurrence rate and patients’ survival.

L’ABLAZIONE CON RADIOFREQUENZA NEL CARCINOMA PANCREATICO IN STADIO III: UNA NUOVA VIA DA SEGUIRE? Frigerio I. Il carcinoma del pancreas ha una prognosi infausta anche quando la diagnosi è precoce. Viene considerata una malattia sistemica anche nei casi di neoplasia localizzata. L’intervento chirurgico gioca è l’unica chance di cura per i pazienti candidabili a chirurgia radicale mentre se sono presenti metastasi a distanza la chemioterapia palliativa è il trattamento di scelta. Rimane una grossa fetta di pazienti affetti da neoplasia localmente avanzata: posso essi beneficiare di un trattamento locale? Abbiamo trattato con radiofrequenza i pazienti affetti da adenocarcinoma pancreatico in stadio III: il primo passo è stato definire un modello riproducibile, efficace e sicuro. L’obietivo è stato raggiunto con i primi 50 pazienti, con un tasso di complicanze legate alla procedura del 12% e una mortalità del 2%. Abbiamo intuito che questi pazienti da noi trattati sembravano avere una sopravvivenza maggiore dell’attesa e, indagando questo dato nei primi 100 pazienti è emerso che la sopravvivenza complessiva è stata di 20 mesi e quella specifica legata alla malattia è stata di 23 mesi, significativamente maggiore I quella dei pazienti sottoposti a radio-chemioterapia tradizionale. Al momento attuale abbiamo trattato 182 pazienti senza variazioni significative delle mortalitò, morbidità e sopravvivenza. La RFA viene sempre associata alla chemioterapia sistemica e alla radioterapia esterna: la RFA costituisce un elemento del trattamento multimodale che riteniamo essere indispensabile nella cura del cancro del pancreas. Un aspetto molto interessante è emerso dagli studi di vari gruppi in questi anni in cui noi ci siamo deidcati alla radiofrequenza: l’immunomodulazione operata dalla RFA che può modificare la storia naturale della malattia. Riteniamo fondamentale l’approfondimento di questo aspetto oltre che l’attuazione di uno studio randomizzato che confermi o meno i risultati osservazionali sulle sopravvivenze.
RADIOFREQUENCY ABLATION IN STAGE III PANCREATIC CARCINOMA: A NEW PATH TO FOLLOW? Frigerio I. Pancreatic cancer has a poor prognosis even when diagnosis is made at early stages because of its systemic nature. Surgery plays an essential role when resection is feasible and palliative chemotherapy is supportive for metastatic disease. May the large group of patients with locally advanced disease benefit of a local treatment? We applied radiofrequency to ablate locally advanced pancreatic carcinoma: we first defined a reproducible and safe model of the technique by treating 50 patients. In this first part of our study mortality rate 2% was and RFA-related morbidity rate was 12%. Because of the feeling that these patients survived longer than expected we looked at survival rate and found that overall survival in the first 100 patients was 20 months and disease specific survival was 23 months, significantly higher than survival of patients undergone to traditional therapy. Up to now we have treated 182 patients with no significative differences in morbidity and mortality rate and survival rate. RFA is always associated to systemic chemotherapy and external radiotherapy. RFA alone is not enough but it is one part of a multimodality treatment which includes chemo and radiotherapy. Different aspects related to interaction between RFA and cancer arose since when we started in 2007: the most promising is the immune modulation operated by RFA. We think that future studies must investigate this field together with a randomized study that will confirm or not this impressive data of survival rate.

碩士
國立清華大學
化學工程學系所
105
Subcutaneous abscesses are focal bacterial infections that are often accompanied with the acidified microenvironment (pH 6-6.6). Two common applied therapies for the abscess management are incision-drainage and systemic administration of antibiotics. However, incision-drainage is a laborious and painful process for patients. Additionally, systemic antibiotic treatment is often accompanied by the evolution of bacterial antibiotic resistance. Therefore, it is an unmet need to develop a reliable antibacterial system to deal with the infections caused by antibiotic-resistant pathogens. The present study reports a system of glycol chitosan-modified, indocyanine green-loaded PLGA nanoparticles (GIP-NPs). According to the physicochemical analysis, this system demonstrates good results in photothermal effect, biocompatibility, pH-response and shelf life. Upon encountering of the acidic environment, GIP-NPs undergo a surface-charge conversion and induce the bacteria-specific aggregation without absorption to the surrounding normal cells. After near-infrared (NIR) irradiation, GIP-NPs can generate local hyperthermia and cause irreversible damage to bacteria. It also shows higher antibacterial effect compared with simply increasing bulk temperature. These experimental results reveal the strong potential of GIP-NPs for the antibacterial therapy in the next generation.