RESUMEN
This study aims to evaluate the histological changes in the nasal mucosa post Tracheostomy. A prospective observational study was done on 30 patients undergoing Tracheostomy after obtaining written informed consent from patients/legally accepted representatives. Prior to Tracheostomy, anterior rhinoscopy was done, and findings were noted; nasal mucosal biopsy was obtained from the inferior turbinate. The patients enrolled were followed up for four weeks, and in the patients still having Tracheostomy, repeat inferior turbinate biopsies were taken and compared. Statistically significant atrophy of lining epithelium was seen in 80% of the subjects, i.e., pseudostratified lining epithelium at Baseline with multilayered appearance changed to a single layer of flattened cells at follow-up. There was also a marked reduction in the number of seromucinous glands in the stroma at follow-up in 80% of the subjects. Additionally, fibrosis in the stroma was noted in 43.3% of subjects at follow-up. The results from this study indicate that Tracheostomy, likely as a result of nasal airflow deprivation, brings about significant changes in the microanatomy of the nasal airway. The extent of this causation and its implication in nasal pathology must be studied in larger populations with extended follow-up periods.
RESUMEN
PURPOSE: To investigate the role of NRF2 signalling in conferring superior prognosis in patients with HPV positive (HPV+ve) head & neck squamous cell carcinomas (HNSCC) compared to HPV negative (HPV-ve) HNSCC and develop molecular markers for selection of HPV+ve HNSCC patients for treatment de-escalation trials. METHODS: NRF2 activity (NRF2, KEAP1, and NRF2-transcriptional targets), p16, and p53 levels between HPV+ve HNSCC and HPV-ve HNSCC in prospective and retrospective tumor samples as well as from TCGA database were compared. Cancer cells were transfected with HPV-E6/E7 plasmid to elucidate if HPV infection represses NRF2 activity and sensitizes to chemo-radiotherapy. RESULTS: Prospective analysis revealed a marked reduction in expression of NRF2, and its downstream genes in HPV+ve tumors compared to HPV-ve tumors. A retrospective analysis by IHC revealed significantly lower NQO1 in p16high tumors compared to p16low tumors and the NQO1 expression correlated negatively with p16 and positively with p53. Analysis of the TCGA database confirmed low constitutive NRF2 activity in HPV+ve HNSCC compared to HPV-ve HNSCC and revealed that HPV+ve HNSCC patients with 'low NQO1' expression showed better overall survival compared to HPV+ve HNSCC patients with 'high NQO1' expression. Ectopic expression of HPV-E6/E7 plasmid in various cancer cells repressed constitutive NRF2 activity, reduced total GSH, increased ROS levels, and sensitized the cancer cells to cisplatin and ionizing radiation. CONCLUSION: Low constitutive NRF2 activity contributes to better prognosis of HPV+ve HNSCC patients. Co-expression of p16high, NQO1low, and p53low could serve as a predictive biomarker for the selection of HPV + ve HNSCC patients for de-escalation trials.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Proteínas Oncogénicas Virales , Infecciones por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Virus del Papiloma Humano , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Neoplasias de Cabeza y Cuello/genética , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/metabolismo , Carcinoma de Células Escamosas/metabolismo , Estudios Retrospectivos , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Oncogénicas Virales/genética , Proteínas Oncogénicas Virales/metabolismoRESUMEN
Vascular headache and chronic rhinosinusitis (CRS) are diseases that share similar symptoms and demographics, including headache, facial pain and nasal symptoms. Contribution of chronic sinusitis as a cause of chronic headache is controversial, as there are scarce studies to know incidence of vascular headache in patients with CRS. To evaluate incidence of vascular headache in patients with CRS. Using descriptive study design, group of 100 patients with symptoms of CRS with headache were included in study. Patients underwent surgical management and 3% managed medically. Patients were assessed for associated factors with headache and further evaluated for persistence of headache postoperatively. Inferential statistics was done by Chi square test using SPSS for Windows Software (Version 21.0). Leading symptoms of CRS were headache (100%), nasal obstruction (93%), and nasal discharge (90%). Pre-treatment 25% had exposure to sunlight as aggravating factor and associated nausea vomiting in 30%. Post-treatment, follow-up at 6 months, 20% reported persisting headache, with duration of headache >1 year in 37.5% (p = 0.01). Those with pre-operative sunlight exposure as aggravating factor, headache persisted in 60% (p < 0.0001) and those with nausea/vomiting pre-treatment; headache persisted in 56.7% (p < 0.0001). These results were statistically significant. In CRS patients who had other factors contributing to headache like duration of headache more than 1 year, associated nausea/vomiting, and aggravating factors like exposure to sunlight, headache persisted after medical and surgical treatment of CRS. It signifies that 20% CRS patients with headache were having co existing vascular headache.