Three-dimensional collagen-based scaffold model to study the microenvironment and drug-resistance mechanisms of oropharyngeal squamous cell carcinomas

Objective:Squamous cell carcinoma(SCC)represents the most common histotype of all head and neck malignancies and includes oropharyngeal squamous cell carcinoma(OSCC),a tumor associated with different clinical outcomes and linked to human papilloma virus(HPV)status.Translational research has few available in vitro models with which to study the different pathophysiological behavior of OSCCs.The present study proposes a 3-dimensional(3 D)biomimetic collagen-based scaffold to mimic the tumor microenvironment and the crosstalk between the extracellular matrix(ECM)and cancer cells.Methods:We compared the phenotypic and genetic features of HPV-positive and HPV-negative OSCC cell lines cultured on common monolayer supports and on scaffolds.We also explored cancer cell adaptation to the 3 D microenvironment and its impact on the efficacy of drugs tested on cell lines and primary cultures.Results:HPV-positive and HPV-negative cell lines were successfully grown in the 3 D model and displayed different collagen fiber organization.The 3 D cultures induced an increased expression of markers related to epithelial–mesenchymal transition(EMT)and to matrix interactions and showed different migration behavior,as confirmed by zebrafish embryo xenografts.The expression of hypoxia-inducible factor 1α(1α)and glycolysis markers were indicative of the development of a hypoxic microenvironment inside the scaffold area.Furthermore,the 3 D cultures activated drug-resistance signaling pathways in both cell lines and primary cultures.Conclusions:Our results suggest that collagen-based scaffolds could be a suitable model for the reproduction of the pathophysiological features of OSCCs.Moreover,3 D architecture appears capable of inducing drug-resistance processes that can be studied to better our understanding of the different clinical outcomes of HPV-positive and HPV-negative patients with OSCCs.

Transoral robotic surgery for obstructive sleep apnea syndrome: Principles and technique

Objective:The present study is a review of transoral robotic surgery (TORS) for the treatment of obstructive sleep apnea-hypopnea syndrome (OSAHS).Methods:The review presents the experience of the robotic center that developed the technique with regards to patient selection,surgical method,and post-operative care.In addition,the review provides results of a systematic review and meta-analysis of the complications and clinical outcomes of TORS when applied in the management of OSAHS.Results:The rate of success,defined as 50％ reduction of pre-operative AHI and an overall AHI ＜20 events/h,is achieved in up to 76.6％ of patients with a range between 53.8％ and 83.3％.The safety of this approach is reasonable as the main complication (bleeding) affected 4.2％ of patients (range 4.2％-5.3％).However,transient dysphagia (7.2％;range 5％-14％) does compromise the quality of life and must be discussed with patients preoperatively.Conclusions:TORS for the treatment of OSAHS appears to be a promising and safe procedure for patients seeking an alternative to traditional therapy.Appropriate patient selection remains an important consideration for successful implementation of this novel surgical approach requiring further research.