Cytotoxic response of tumor-infiltrating lymphocytes of head and neck cancer slice cultures under mitochondrial dysfunction.

Background: Head and neck squamous cell carcinomas (HNSCC) are highly heterogeneous tumors. In the harsh tumor microenvironment (TME), metabolic reprogramming and mitochondrial dysfunction may lead to immunosuppressive phenotypes. Aerobic glycolysis is needed for the activation of cytotoxic T-cells and the absence of glucose may hamper the full effector functions of cytotoxic T-cells. To test the effect of mitochondrial dysfunction on cytotoxic T cell function, slice cultures (SC) of HNSCC cancer were cultivated under different metabolic conditions. Methods: Tumor samples from 21 patients with HNSCC were collected, from which, SC were established and cultivated under six different conditions. These conditions included high glucose, T cell stimulation, and temporarily induced mitochondrial dysfunction (MitoDys) using FCCP and oligomycin A with or without additional T cell stimulation, high glucose and finally, a control medium. Over three days of cultivation, sequential T cell stimulation and MitoDys treatments were performed. Supernatant was collected, and SC were fixed and embedded. Granzyme B was measured in the supernatant and in the SC via immunohistochemistry (IHC). Staining of PD1, CD8/Ki67, and cleaved-caspase-3 (CC3) were performed in SC. Results: Hematoxylin eosin stains showed that overall SC quality remained stable over 3 days of cultivation. T cell stimulation, both alone and combined with MitoDys, led to significantly increased granzyme levels in SC and in supernatant. Apoptosis following T cell stimulation was observed in tumor and stroma. Mitochondrial dysfunction alone increased apoptosis in tumor cell aggregates. High glucose concentration alone had no impact on T cell activity and apoptosis. Apoptosis rates were significantly lower under conditions with high glucose and MitoDys (p=0.03). Conclusion: Stimulation of tumor-infiltrating lymphocytes in SC was feasible, which led to increased apoptosis in tumor cells. Induced mitochondrial dysfunction did not play a significant role in the activation and function of TILs in SC of HNSCC. Moreover, high glucose concentration did not promote cytotoxic T cell activity in HNSCC SC.

Diagnosis, Treatment and Follow-Up of Sinonasal Leiomyomas: A Systematic Review.

BACKGROUND: Leiomyomas are benign smooth muscle tumors that are rarely diagnosed in the nasal cavity and paranasal sinuses. OBJECTIVE: This systematic review summarizes the histopathologic and clinical tumor characteristics, surgical management, and follow-up of sinonasal leiomyomas. METHODS: A systematic review of the literature on sinonasal leiomyoma was performed by applying the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Studies that met the inclusion criteria were assessed for level of evidence. Patient demographics, clinical and pathological tumor characteristics, primary intervention, and results of follow-up were evaluated. RESULTS: Forty studies including 84 patients with sinonasal leiomyoma were identified. The tumor was most often located in the nasal cavity (47/84, 56%) originating from the inferior turbinate (32/84, 38%). Patients mostly presented with symptoms originating from an intranasal mass, including recurrent epistaxis (41/84, 49%), nasal obstruction (43/84, 51.2%), and localized facial or head pain (25/84, 29.8%). Surgery was performed in all cases. An endoscopic approach was most frequently chosen. Recurrence occurred only twice (2.4%). Morbidity was noted in 2 cases (2.4%) following postoperative bleeding and 1 (1.2%) case following a CSF leak. CONCLUSION: Sinonasal leiomyomas are neoplasms of the smooth muscle manifesting clinically with recurrent epistaxis and nasal obstruction. Management goal is total resection with clear margins to avoid local recurrence.

Modified vacuum-assisted closure (EndoVAC) therapy for treatment of pharyngocutaneous fistula: Case series and a review of the literature.

BACKGROUND: Pharyngocutaneous fistula is a potential life-threatening complication following head and neck surgery. There is only limited evidence about the efficacy of vacuum-assisted closure (VAC) therapy and endoscopic vacuum-assisted closure (EndoVAC) therapy for the treatment of pharyngocutaneous fistulas. METHODS: In this article, we report on a consecutive case series of six male patients with pharyngocutaneous fistula treated with a modified outside-in EndoVAC technique. We also present a review of the current related literature. RESULTS: EndoVAC therapy alone was successful in five of the six patients (83.3%) with a median duration of EndoVAC therapy of 18.5 days (range: 7 to 32 days) and a median number of EndoVAC sponge changes of 4 (range: 1 to 9 changes). One patient needed additional reconstructive surgery after prior radiochemotherapy and jejunal transfer. No treatment-related complications were observed. CONCLUSION: EndoVAC therapy is an easy-to-perform, safe procedure for the treatment of pharyngocutaneous fistulae.