Objetivo: Comparar o tratamento cirúrgico convencional das varizes de membros inferiores com a escleroterapia com espuma ecoguiada nos pacientes com úlcera venosa. Como objetivo secundário, foi comparada a incidência de complicações com os métodos empregados e a melhora na qualidade de vida após a realização dos procedimentos. Casuística e Métodos: Foi realizado um estudo randomizado e prospectivo de 49 pacientes com úlceras ativas (C6), que foram submetidos ao tratamento cirúrgico (28 membros) ou escleroterapia espuma (23 membros), tendo como desfechos a cicatrização de úlceras de origem venosa, complicações do tratamento e qualidade de vida,. Os pacientes completaram o Questionário Aberdeen Veias Varicosas (QAVV), o escore de severidade clínica venoso (ESCV) e o Escore de Incapacidade Venosa (EIV). Resultados: A média e desvio padrão de acompanhamento foi de 502 ± 220 dias. A úlcera cicatrizou em 100% e 91,3% dos doentes tratados com cirurgia ou escleroterapia espuma, respectivamente (P > 0,05). QAVV, ESCV e EIV melhoraram em ambos os grupos após o tratamento. Não houve diferenças significativas no resultado final do QAVV, ESCV e EIV entre os dois grupos, vários meses após os procedimentos (p = 0,45, 0,58 e 0,66, respectivamente; Mann- Whitney U). As complicações ocorreram em 14,2% e 13,0% nos grupos cirúrgico e escleroterapia com espuma, respectivamente. Conclusão: A escleroterapia com espuma não foi inferior ao tratamento cirúrgico de úlceras venosas. Portanto a escleroterapia é uma alternativa ao tratamento cirúrgico, particularmente adequada para pacientes de alto risco cirúrgico que apresentam insuficiência venosa avançada e úlcera ativa / Objective: To compare the results of varicose vein treatment using ultrasoundguided foam sclerotherapy versus conventional surgery in patients with venous ulcers. As a secondary outcome, we compared the incidence of complications related to the employed technique and improvements in quality of life after the procedures. Methods: A randomized and prospective study was conducted in 49 patients with active venous ulcers (C6), submitted to surgical treatment (28 limbs) or foam sclerotherapy (23 limbs). The primary outcomes analysed included healing of venous ulcer, treatment complications and improvements in quality of life. All patients completed the Aberdeen Varicose Veins Questionnaire (AVVQ), the Venous Clinical Severity score (VCSS) and Venous Disability Score (VDS). Results: The mean and standard deviation follow-up was 502 ± 220 days. Ulceration healing was observed in 100% and 91.3% of patients treated with surgery or foam sclerotherapy, respectively (P > 0.05). AVVQ, VCSS and VDS improved in both groups following treatment. There were no significant differences in AVVQ, VCSS and VDS between the two groups several months after the procedures (p = 0,45, 0.58 and 0.66, respectively; Mann-Whitney U test). Complications occurred in 14.2% and 13.0% in the surgical and foam sclerotherapy groups, respectively. Conclusion: Sclerotherapy was non-inferior to surgical treatment in the management of venous ulcers. Therefore sclerotherapy can be considered an alternative to surgical treatment, especially in high surgical risk patients presenting with advanced venous insufficiency and an active ulcer

Objetivo: Comparar o tratamento cirúrgico convencional das varizes de membros inferiores com a escleroterapia com espuma ecoguiada nos pacientes com úlcera venosa. Como objetivo secundário, foi comparada a incidência de complicações com os métodos empregados e a melhora na qualidade de vida após a realização dos procedimentos. Casuística e Métodos: Foi realizado um estudo randomizado e prospectivo de 49 pacientes com úlceras ativas (C6), que foram submetidos ao tratamento cirúrgico (28 membros) ou escleroterapia espuma (23 membros), tendo como desfechos a cicatrização de úlceras de origem venosa, complicações do tratamento e qualidade de vida,. Os pacientes completaram o Questionário Aberdeen Veias Varicosas (QAVV), o escore de severidade clínica venoso (ESCV) e o Escore de Incapacidade Venosa (EIV). Resultados: A média e desvio padrão de acompanhamento foi de 502 ± 220 dias. A úlcera cicatrizou em 100% e 91,3% dos doentes tratados com cirurgia ou escleroterapia espuma, respectivamente (P > 0,05). QAVV, ESCV e EIV melhoraram em ambos os grupos após o tratamento. Não houve diferenças significativas no resultado final do QAVV, ESCV e EIV entre os dois grupos, vários meses após os procedimentos (p = 0,45, 0,58 e 0,66, respectivamente; Mann- Whitney U). As complicações ocorreram em 14,2% e 13,0% nos grupos cirúrgico e escleroterapia com espuma, respectivamente. Conclusão: A escleroterapia com espuma não foi inferior ao tratamento cirúrgico de úlceras venosas. Portanto a escleroterapia é uma alternativa ao tratamento cirúrgico, particularmente adequada para pacientes de alto risco cirúrgico que apresentam insuficiência venosa avançada e úlcera ativa / Objective: To compare the results of varicose vein treatment using ultrasoundguided foam sclerotherapy versus conventional surgery in patients with venous ulcers. As a secondary outcome, we compared the incidence of complications related to the employed technique and improvements in quality of life after the procedures. Methods: A randomized and prospective study was conducted in 49 patients with active venous ulcers (C6), submitted to surgical treatment (28 limbs) or foam sclerotherapy (23 limbs). The primary outcomes analysed included healing of venous ulcer, treatment complications and improvements in quality of life. All patients completed the Aberdeen Varicose Veins Questionnaire (AVVQ), the Venous Clinical Severity score (VCSS) and Venous Disability Score (VDS). Results: The mean and standard deviation follow-up was 502 ± 220 days. Ulceration healing was observed in 100% and 91.3% of patients treated with surgery or foam sclerotherapy, respectively (P > 0.05). AVVQ, VCSS and VDS improved in both groups following treatment. There were no significant differences in AVVQ, VCSS and VDS between the two groups several months after the procedures (p = 0,45, 0.58 and 0.66, respectively; Mann-Whitney U test). Complications occurred in 14.2% and 13.0% in the surgical and foam sclerotherapy groups, respectively. Conclusion: Sclerotherapy was non-inferior to surgical treatment in the management of venous ulcers. Therefore sclerotherapy can be considered an alternative to surgical treatment, especially in high surgical risk patients presenting with advanced venous insufficiency and an active ulcer

Tumorigenesis is often caused by the dysregulation of developmental pathways that are activated during repair, a process that recapitulates development. The Hedgehog (Hh) pathway is a signalling pathway essential for cell patterning and identity during embryogenesis. Activation of Hh signalling has been reported in small cell lung cancer progression, but the role of the Hh receptor, Patched1 (Ptch1), remains poorly understood. Therefore, it is imperative that we understand how Ptch1 is involved in development and tissue repair in order to understand its roles in cancer. This project aimed to study the role of Ptch1 during the branching process of lung development and in the regeneration of airway epithelial cells. A conditional knockout approach was utilised to excise Ptch1 by crossing Ptch1 conditional mice with Dermo1-Cre mice (Dermo1Cre+/-;Ptch1lox/lox), thereby activating the Hh pathway in the mesenchyme, independent of ligand. Dermo1Cre+/-;Ptch1lox/lox embryos died at E12.0 and showed secondary lung branching arrest leading to lobe formation defects. Expression of Ptch1, Gli1 and Foxf1 were shown to be upregulated in both proximal and distal lung mesenchyme, indicating inappropriate pathway activation and disruption of the Hh gradient. Fgf10 expression was spatially reduced in Dermo1Cre+/-;Ptch1lox/lox lungs and the addition of Fgf10 to these lungs in culture showed partial restoration of branching, thus Hh signalling was shown to regulate branching via Fgf10. Due to the patterning defect associated with our in vivo model, we took an in vitro approach to delete Ptch1 in lung explants cultures. This also showed reduced branching and validated that mesenchymal proliferation was enhanced after Ptch1 deletion, consistent with the previously reported role of Hh signalling in mesenchymal cell survival. Small cell lung cancer originates in the proximal lung and has been linked to aberrant repair processes. Therefore, Hh signalling in proximal airway repair was investigated. Ptch1 expressing cells were detected in the bronchial epithelium and stroma during homeostasis. But these cells were not detected following polidocanol-induced injury in the murine nasal septum and lung. However during naphthalene-induced repair, Ptch1 expressing cells were detected in the regenerating bronchial epithelium, suggesting that Hh dependent progenitors respond specifically to naphthalene-induced damage and perhaps are pulmonary neuroendocrine or variant Clara cells. Therefore, this project has provided insight into how Ptch1 patterns lung branching and lobe specification during development and also highlights the importance of Ptch1 in pulmonary epithelial regeneration.