Skin cancers represent the most frequent type of neoplasms worldwide, affecting over one third of fair-skinned individuals. Several risk factors have already been implicated in the development of cutaneous malignancies, including skin phototype, sun exposure, personal and/or familial history, immunosuppression, several drugs and some specific genodermatoses (e.g. xeroderma pigmentosum, epidermolysis bullosa (EB), Gorlin-Goltz syndrome). The first-line treatment of choice for cutaneous neoplasms is surgical removal, whenever possible. However, demolitive surgery is often necessary for radical excision, which implicitly implies possible complications in terms of reconstruction and wound healing. Not only tumor size and anatomical location can limit the choice of the correct reconstructive strategy, but also other obstacles are represented by the presence of other conditions predisposing to impaired cutaneous healing; among these: diabetes, peripheral vascular disease, smoking habits, connective tissue disorders, systemic corticosteroids, congenital and/or genetically acquired conditions characterized by an impairment in wound healing. The present work fits perfectly into the research for innovative strategies for wound healing in the dermato-oncological context. With regards to this, we aimed at investigating 3 principal setting: 1) the use of mesenchymal stem cells as cell-based therapies for wound healing; 2) the use if acellular dermal regeneration templates; 3) surgical treatment of skin neoplasms in patients affected by epidermolysis bullosa. In the first part of this PhD dissertation, several studies on mesenchymal stem cells are presented, with the aim of demonstrating their immunomodulatory and regenerative properties, not only in terms of extracellular matrix production but also of pro-epithelizing properties . A second result section is dedicated to regenerative dermal templates. In particular, two main clinical studies have been included: the first one aimed at comparing two of the most commonly used acellular dermal matrices in terms of clinical and histopathological outcomes, while the second one being focused on the cost-benefit ratio of such products in terms of patient satisfaction. We also described the in vitro combination of acellular dermal substitutes and mesenchymal stromal cells as possible novel therapeutic strategy for wound healing. Finally, the third part of the present work is aimed at describing the clinical postoperative outcomes in patient affected by junctional and dystrophic forms of epidermolysis bullosa congenita undergoing surgical resection of cutaneous squamous cell carcinomas, based on the type of treatment received. Despite not being exhaustive of all the available wound healing strategies currently under investigation, the results achieved by the present work bring new insights in the setting of dermatologic surgery both from an oncological and regenerative point of view. A particular attention is also given to special conditions both affecting wound healing and predisposing to skin cancer such as epidermolysis bullosa.
I tumori cutanei sono neoplasie frequenti nella popolazione generale, che colpiscono oltre un terzo dei soggetti di cute chiara. Oltre al fototipo, altri fattori sembrano predisporre all’insorgenza di tumori cutanei, tra cui: fotoesposizione, storia personale o familiare di neoplasie, immunosoppressione, utilizzo di determinati farmaci, alcune genodermatosi. La prima linea di trattamento per qualunque tipo di neoplasia cutanea è sempre l’asportazione chirurgica radicale, ove possibile. In molti casi, tuttavia, si rende necessaria una chirurgia demolitiva che comporta problematiche in termini di ricostruzione e cicatrizzazione. Non solo le dimensioni e la sede della neoplasia possono costituire un limite nella scelta della strategia ricostruttiva, ma anche la presenza di condizioni predisponenti che comportino un’alterata cicatrizzazione; tra queste: diabete, vasculopatia periferica, abitudine tabagica, connettivopatie, terapia corticosteroidea sistemica, o alterazioni congenite/su base genetica del normale wound healing. E’ proprio nella ricerca di strategie di wound healing innovative contesto chirurgico dermato-oncologico che si inquadra il presente lavoro. A questo proposito, sono stati investigati 3 principali ambiti: 1) l’utilizzo di strategie cellulari basate su cellule staminali mesenchimali; 2) l’utilizzo di matrici dermiche acellulari; 3) il trattamento chirurgico dei carcinomi squamocellulari in pazienti affetti da epidermolisi bollosa congenita. Nella prima parte della presente tesi di dottorato verranno descritti alcuni studi in vitro sulle cellule mesenchimali staminali volti a dimostrarne le proprietà rigenerative -non solo in termini di secrezione di matrice extracellulare ma anche di proprietà pro-epitelizzanti- ed immunomodulatorie. Una seconda sezione di risultati è dedicata alle matrici dermiche acellulari. A questo proposito sono stati inclusi due studi clinici, il primo volto a comparare gli outcomes clinici ed istopatologici dei due sostituti di più comune utilizzo, il secondo teso a valutarne il rapporto costi-benefici in termini di soddisfazione del paziente. Viene inoltre descritto uno studio in vitro riguardante l’utilizzo combinato di matrici dermiche acellulari e cellule staminali mesenchimali come possibile strategia innovativa per la guarigione delle ferite. Infine, vengono presentati due studi clinici su pazienti affetti da forme severe di epidermolisi bollosa giunzionale e distrofica trattati chirurgicamente per l’insorgenza di carcinomi squamocellulari volti a valutarne gli outcomes clinici ed il decorso post-operatorio sulla base del tipo di trattamento ricevuto. Sebbene tale trattazione non sia esaustiva di tutte le strategie di wound healing attualmente in studio in ambito di medicina rigenerativa, i risultati ottenuti aprono nuove prospettive nel contesto della chirurgia dermatologica ad indirizzo oncologico e rigenerativo, con un’attenzione particolare attenzione al trattamento degli epiteliomi dei pazienti affetti da epidermolisi bollosa.
Oncologia cutanea e guarigione delle ferite: strategie rigenerative nel contesto dermato-chirurgico / Alessia Paganelli , 2023 Sep 29. 35. ciclo, Anno Accademico 2021/2022.
Oncologia cutanea e guarigione delle ferite: strategie rigenerative nel contesto dermato-chirurgico
paganelli, alessia
2023
Abstract
Skin cancers represent the most frequent type of neoplasms worldwide, affecting over one third of fair-skinned individuals. Several risk factors have already been implicated in the development of cutaneous malignancies, including skin phototype, sun exposure, personal and/or familial history, immunosuppression, several drugs and some specific genodermatoses (e.g. xeroderma pigmentosum, epidermolysis bullosa (EB), Gorlin-Goltz syndrome). The first-line treatment of choice for cutaneous neoplasms is surgical removal, whenever possible. However, demolitive surgery is often necessary for radical excision, which implicitly implies possible complications in terms of reconstruction and wound healing. Not only tumor size and anatomical location can limit the choice of the correct reconstructive strategy, but also other obstacles are represented by the presence of other conditions predisposing to impaired cutaneous healing; among these: diabetes, peripheral vascular disease, smoking habits, connective tissue disorders, systemic corticosteroids, congenital and/or genetically acquired conditions characterized by an impairment in wound healing. The present work fits perfectly into the research for innovative strategies for wound healing in the dermato-oncological context. With regards to this, we aimed at investigating 3 principal setting: 1) the use of mesenchymal stem cells as cell-based therapies for wound healing; 2) the use if acellular dermal regeneration templates; 3) surgical treatment of skin neoplasms in patients affected by epidermolysis bullosa. In the first part of this PhD dissertation, several studies on mesenchymal stem cells are presented, with the aim of demonstrating their immunomodulatory and regenerative properties, not only in terms of extracellular matrix production but also of pro-epithelizing properties . A second result section is dedicated to regenerative dermal templates. In particular, two main clinical studies have been included: the first one aimed at comparing two of the most commonly used acellular dermal matrices in terms of clinical and histopathological outcomes, while the second one being focused on the cost-benefit ratio of such products in terms of patient satisfaction. We also described the in vitro combination of acellular dermal substitutes and mesenchymal stromal cells as possible novel therapeutic strategy for wound healing. Finally, the third part of the present work is aimed at describing the clinical postoperative outcomes in patient affected by junctional and dystrophic forms of epidermolysis bullosa congenita undergoing surgical resection of cutaneous squamous cell carcinomas, based on the type of treatment received. Despite not being exhaustive of all the available wound healing strategies currently under investigation, the results achieved by the present work bring new insights in the setting of dermatologic surgery both from an oncological and regenerative point of view. A particular attention is also given to special conditions both affecting wound healing and predisposing to skin cancer such as epidermolysis bullosa.File | Dimensione | Formato | |
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PHD DISSERTATION AP-2REVISED INVIATA.pdf
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