Expression of Immune Checkpoint Regulators, Cytotoxic T-Lymphocyte Antigen-4, and Programmed Death-Ligand 1 in Epstein-Barr Virus-associated Nasopharyngeal Carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is the most common cancer arising from the nasopharynx with a poor prognosis. Targeting immune checkpoint is one of the new promising lines in cancer treatment. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-ligand 1 (PD-L1) are immune checkpoints that regulate T-cell immune function. AIM: This work aimed to assess the immunohistochemical expression of PD-L1 and CTLA-4 in NPC and their ability to predict survival and response therapy and to check their validity as immunotherapy targets. Twenty-six cases of NPC were studied by immunohistochemistry for PD-L1 and CTLA-4 and by nested polymerase chain reaction followed by DNA sequencing for the presence of EBNA-1 gene of Epstein-Barr virus (EBV). All investigated cases were diagnosed and treated in the Zagazig University Hospital in the period from August 2015 to July 2018. EBNA-1 gene was identified in 84.6% of the cases. Whereas the expression of PD-L1 was noted in 46.2% of all cases studied, 54.6% of EBV-associated NPCs were found to express PD-L1. There was a significant association between PD-L1 expression and the advanced stage of the tumor (P<0.001). CTLA-4 expression was observed in 88.4% of all NPC cases as cytoplasmic staining in both tumor cells and tumor-infiltrating lymphocytes. CTLA-4 expression in lymphocytes was associated with the presence of EBV. A significant association was detected between CTLA-4 and tumor-infiltrating lymphocyte expression on one side and the stage of the tumor on the other. High expression of CTLA-4 was significantly associated with disease progression and worse overall survival. CONCLUSION: PD-L1 and CTLA-4 are adverse prognostic markers in NPC. The authors propose that targeted therapy against PD-L1 and CTLA-4 will be a hopeful therapy for cases of NPC with resistance to concurrent chemoradiation treatment in Egypt, especially EBV-associated cases.

Mastoid Reconstruction With Platelet-Rich Plasma and Bone Pate After Canal Wall Down Mastoidectomy: A Preliminary Report.

OBJECTIVES: Mastoid reconstruction principle had been described to overcome problems of chronic discharging cavity. Different materials were used; nonbiologic materials seem to be less preferred. Platelet-rich plasma (PRP) could promote the regeneration of mineralized tissues. In this work, the authors present a simple and easy technique for mastoid reconstruction with PRP and cortical bone pate. METHODS: The study design is a case series. Patients had mastoid reconstruction after canal wall down mastoidectomy using PRP and cortical bone pate. RESULTS: This study included 21 patients: 9 males, and 12 females. Sixteen patients had left side disease. All surgical procedures were conducted smoothly within 90 to 135 minutes with no stressful events had been reported. At 12 to 16 months of follow-up, external canal stenosis and mastoid fistulas were not reported. Good healing of the tympanic membrane was seen in 18 patients. No radiological signs suggestive of recurrence were detected and the reconstructed mastoid cavity was smooth and well aerated. Residual tympanic membrane perforations were detected in 3 patients. CONCLUSION: Autologous materials (PRP and bone pate pate) after canal wall down mastoidectomy appear to be a reliable and effective choice for mastoid reconstruction.