RESUMO
OBJECTIVE: Investigation of the gustatory function in a large cohort of cochlear implanted patients using lateralized taste-strip tests. PATIENTS AND METHODS: One hundred and seven unilaterally or bilaterally profoundly hearing impaired or deaf patients who received cochlear implants (n = 113) were included in this study. Data on gustometry, subjective gustatory dysfunction, and the detailed surgical procedure were acquired retrospectively. Gustatory function, assessed using lateralized taste-strip tests, was performed the day before, 3 days after cochlear implantation, and on the day of the initial CI adjustment (39 days ±7.3 SD). RESULTS: Averaged taste-strip scores of the cohort declined significantly from preoperatively 12.3 [11.8; 12.7] (mean [95% confidence intervals]) to 10.5 [9.7; 11.2] on the implanted side about 6 weeks after surgery. Patients with intraoperatively exposed and rerouted, or a severed, chorda tympani nerve (CTN) showed significantly reduced unilateral postoperative scores (10.1 [8.8; 11.4] and 9.3 [8.1; 10.5], respectively), when compared to not exposing or to leaving a bony layer over the CTN. Total taste-strip test scores showed a significant decline 6 weeks postoperatively in CI-patients expressing a subjective gustatory dysfunction (from 23.6 [21.4; 25.8] to 17.5 [14.2; 20.8]), as opposed to patients with a documented subjectively normal taste. CONCLUSION: We consider postoperative gustatory dysfunction as a relevant side effect post cochlear implantation, at least within the first month. Taste-strip based gustometry is a suitable diagnostic tool to assess taste function in CI patients and is recommended to be performed routinely. LEVEL OF EVIDENCE: 3, retrospective, nonrandomized follow-up study.
RESUMO
Different studies have shown that HPV16-positive OPSCC can be subdivided based on integration status (integrated, episomal and mixed forms). Because we showed that integration neither affects the levels of viral genes, nor those of virally disrupted human genes, a genome-wide screen was performed to identify human genes which expression is influenced by viral integration and have clinical relevance. Thirty-three fresh-frozen HPV-16 positive OPSCC samples with known integration status were analyzed by mRNA expression profiling. Among the genes of interest, Aldo-keto-reductases 1C1 and 1C3 (AKR1C1, AKR1C3) were upregulated in tumors with viral integration. Additionally, 141 OPSCC, including 48 HPV-positive cases, were used to validate protein expression by immunohistochemistry. Results were correlated with clinical and histopathological data. Non-hierarchical clustering resulted in two main groups differing in mRNA expression patterns, which interestingly corresponded with viral integration status. In OPSCC with integrated viral DNA, often metabolic pathways were deregulated with frequent upregulation of AKR1C1 and AKR1C3 transcripts. Survival analysis of 141 additionally immunostained OPSCC showed unfavorable survival rates for tumors with upregulation of AKR1C1 or AKR1C3 (both p <0.0001), both in HPV-positive (p ≤0.001) and -negative (p ≤0.017) tumors. OPSCC with integrated HPV16 show upregulation of AKR1C1 and AKR1C3 expression, which strongly correlates with poor survival rates. Also in HPV-negative tumors, upregulation of these proteins correlates with unfavorable outcome. Deregulated AKR1C expression has also been observed in other tumors, making these genes promising candidates to indicate prognosis. In addition, the availability of inhibitors of these gene products may be utilized for drug treatment.
