Moderate Dose Irradiation Induces DNA Damage and Impairments of Barrier and Host Defense in Nasal Epithelial Cells in vitro.

Purpose: Radiotherapy (RT) is the mainstay treatment for head and neck cancers. However, chronic and recurrent upper respiratory tract infections and inflammation have been commonly reported in patients post-RT. The underlying mechanisms remain poorly understood. Method and Materials: We used a well-established model of human nasal epithelial cells (hNECs) that forms a pseudostratified layer in the air-liquid interface (ALI) and exposed it to single or repeated moderate dose γ-irradiation (1Gy). We assessed the DNA damage and evaluated the biological properties of hNECs at different time points post-RT. Further, we explored the host immunity alterations in irradiated hNECs with polyinosinic-polycytidylic acid sodium salt (poly [I:C]) and lipopolysaccharides (LPS). Results: IR induced DNA double strand breaks (DSBs) and triggered DNA damage response in hNECs. Repeated IR significantly reduced basal cell proliferation with low expression of p63/KRT5 and Ki67, induced cilia loss and inhibited mucus secretion. In addition, IR decreased ZO-1 expression and caused a significant decline in the transepithelial electrical resistance (TEER). Moreover, hyperreactive response against pathogen invasion and disrupted epithelial host defense can be observed in hNECs exposed to repeated IR. Conclusion: Our study suggests that IR induced prolonged structural and functional impairments of hNECs may contribute to patients post-RT with increased risk of developing chronic and recurrent upper respiratory tract infection and inflammation.

Comparison between anterolateral thigh free flap and jejunal flap for tissue reconstruction in patients underwent resection of pharyngoesophageal squamous cell carcinoma after radiotherapy failure: a retrospective study.

BACKGROUND: Anterolateral thigh (ALT) free flap and jejunal flap (JF) were commonly used in tissue reconstruction for pharyngoesophageal squamous cell carcinoma (PESCC) with worsening tissue adhesion and necrosis after radiotherapy failure. However, the results of tissue reconstruction and postoperative complications of these two flaps are controversial. The purpose of this study was to compare outcomes between group ALT free flap and group JF in PESCC after radiotherapy failure. METHODS: Intraoperative information and postoperative outcomes of patients with PESCC after radiotherapy failure who underwent ALT and JF reconstruction from January 2005 to December 2019 were compared and analyzed. RESULTS: The defect size of ALT (Numbers, 34) and JF (Numbers, 31) was 36.19 ± 11.35 cm2 and 35.58 ± 14.32 cm2 (p = 0.884), respectively. ALT and JF showed no significant difference in operation time (p = 0.683) and blood loss (p = 0.198). For postoperative outcomes within 30 days both in recipient site and donor site including wound bleeding, wound dehiscence, wound infection, and pharyngocutaneous fistula, ALT free flap and JF showed similar results. Flap compromise (Numbers, 2 VS.3, p = 0.663), flap take backs (Numbers, 1 VS.1, p = 1.000), partial flap failures (Numbers, 4 VS.2, p = 0.674), and total flap failures (Numbers, 0 VS.0, p = 1.000) showed no difference between the two groups. In addition, no significance was found in hypoproteinemia between the two groups (Numbers, 4 VS.2, p = 0.674). ALT free flap was not statistically different from JF in the incidence of dysphagia at the postoperative 6 months (Numbers of liquid diet, 5VS.5; Numbers of partial tube feeding, 6VS.7; Numbers of total tube feeding, 3VS.1, p = 0.790) and 12 months (Numbers of liquid diet, 8VS.7; Numbers of partial tube feeding, 8VS.7; Numbers of total tube feeding, 5VS.5, p = 0.998). The cause of dysphagia not found to differ between the two groups both in postoperative 6 months (p = 0.814) and 12 months (p = 0.845). CONCLUSION: Compared with JF, ALT free flap for PESCC patients after radiotherapy failure showed similar results in postoperative outcomes. ALT free flap may serve as a safe and feasible alternative for PESCC patients after radiotherapy failure.

Abnormal Expression of YAP Is Associated With Proliferation, Differentiation, Neutrophil Infiltration, and Adverse Outcome in Patients With Nasal Inverted Papilloma.

BACKGROUND: Nasal inverted papilloma (NIP) is a common benign tumor. Yes-associated protein (YAP) is the core effector molecule of the Hippo pathway, which regulates the proliferation and differentiation of airway epithelium. While its role in proliferation may be connected to NIP formation, no definitive association has been made between them. METHODS: We compared the difference of YAP expression and proliferation level between the control inferior turbinate, NP (nasal polyps), and NIP groups. In addition, we further used PCR, immunofluorescence, and immunohistochemistry to investigate YAP's role in the proliferation and differentiation of the nasal epithelium and inflammatory cell infiltration, correlating them with different grades of epithelial remodeling. We further used an IL-13 remodeling condition to investigate YAP's role in differentiation in an in vitro air-liquid interface (ALI) human nasal epithelial cell (hNECs) model. Finally, we also explored the correlation between YAP expression and clinical indicators of NIP. RESULTS: The expression of YAP/active YAP in the NIP group was significantly higher than that in the NP group and control group. Moreover, within the NIP group, the higher grade of epithelial remodeling was associated with higher YAP induced proliferation, leading to reduced ciliated cells and goblet cells. The finding was further verified using an IL-13 remodeling condition in differentiating ALI hNECs. Furthermore, YAP expression was positively correlated with proliferation and neutrophil infiltration in NIP. YAP expression was also significantly increased in NIP patients with adverse outcomes. CONCLUSION: Abnormal expression of YAP/active YAP is associated with proliferation, differentiation, neutrophil infiltration, and adverse outcome in NIP and may present a novel target for diagnosis and intervention in NIP.