The presence of bile is not an uncommon finding in acidic oesophageal and extra‐oesophageal refluxate, possibly affecting the hypopharyngeal mucosa and leading to neoplastic events. We recently demonstrated that acidic bile (pH ≤ 4.0) can induce NF‐κB activation and oncogenic mRNA phenotype in normal hypopharyngeal cells and generate premalignant changes in treated hypopharyngeal mucosa. We hypothesize that curcumin, a dietary inhibitor of NF‐κB, may effectively inhibit the acidic bile‐induced cancer‐related mRNA phenotype, in treated human hypopharyngeal primary cells (HHPC), supporting its potential preventive use in vivo. Luciferase assay, immunofluorescence, Western blot, qPCR and PCR microarray analysis were used to explore the effect of curcumin in HHPC exposed to bile (400 μmol/L) at acidic and neutral pH. Curcumin successfully inhibited the acidic bile‐induced NF‐κB signalling pathway (25% of analysed genes), and overexpression of NF‐κB transcriptional factors, c‐REL, RELA(p65), anti‐apoptotic bcl‐2, oncogenic TNF‐α, EGFR, STAT3, WNT5A, ΔNp63 and cancer‐related IL‐6. Curcumin effectively reduced bile‐induced bcl‐2 overexpression at both acidic and neutral pH. Our novel findings suggest that, similar to pharmacologic NF‐κB inhibitor, BAY 11‐7082, curcumin can suppress acidic bile‐induced oncogenic mRNA phenotype in hypopharyngeal cells, encouraging its future in vivo pre‐clinical and clinical explorations in prevention of bile reflux‐related pre‐neoplastic events mediated by NF‐κB.
Objectives: To identify factors associated with positive margins following surgical management of sinonasal squamous cell carcinoma (SNSCC), especially with regard to endoscopic treatment.Methods: In a retrospective analysis of adult patients with clinically staged tumor (T)1 to T4a SNSCC within the National Cancer Database (NCDB) from 2004 to 2014, factors were associated with positive margins using multivariable binary logistic regression. Cases from 2010 to 2014 had surgical approach (open vs. endoscopic) available and were analyzed in a subgroup to assess the association of surgical approach with margin status. The association of margin status with overall survival (OS) and additional therapy administration was also assessed.Results: We identified 2,968 cases, of which 807 (27.2%) had positive margins. On multivariable analysis, factors associated with positive margins included higher T stage (T4a vs. T1: odds ratio [OR] 2.768 [95% CI 2.143-3.577]), less differentiated tumors (poorly differentiated vs. well differentiated: OR 1.403 [95% CI 1.060-1.856]), and tumors in the ethmoid sinus (vs. nasal cavity; OR 1.889 [95% CI 1.305-2.734]). Cases treated at higher volume facilities (HVFs) were associated with a lower likelihood of positive margins (OR 0.716 [95% CI 0.582-0.881]). Positive margins were associated with decreased OS (hazard ratio 1.672 [95% CI 1.464-1.908]) and an increased rate of additional therapy (OR 1.966 [95% confidence interval 1.597-2.421]). An endoscopic approach was not associated with an increased likelihood of obtaining positive margins (vs. open; OR 1.151 [0.903-1.651]).Conclusion: Positive margins were less likely when performed at HVFs and more likely in the ethmoid sinus than other subsites. Importantly, there was no association between positive margins and surgical approach. Endoscopic surgery may offer a safe, less invasive alternative to open surgery for select patients.
Objective To evaluate postoperative opiate use and patients’ opinions regarding pain management after endoscopic sinus surgery (ESS). Study Design Case series with planned data collection. Setting Tertiary referral medical center. Subjects and Methods We prospectively evaluated postoperative opiate utilization in adults undergoing ESS over a 2-year period at an academic medical facility. Exclusion criteria included use of nasal packing, intracranial or orbital procedures, tumor surgery, and any use of endoscopic drills. All patients underwent bilateral maxillary antrostomy, total ethmoidectomy, sphenoidotomy, and frontal sinusotomy with or without septoplasty. Patients were discharged with 30 oxycodone-acetaminophen (5-325 mg) and a survey assessing pain and narcotic/nonnarcotic use on postoperative days 0 to 7. Results A total of 64 patients completed surveys. Mean ± SD narcotic use over the 7-day postoperative period was 7.7 ± 7.6 pills. Patients with high narcotic use (>6 pills total) had no differences in demographic or surgical factors from those with low use (≤6 pills) but did report a higher level of postoperative day 1 pain (4.8 ± 1.1 vs 2.0 ± 1.4, P < .001). Narcotic use declined during this period, with <30% of patients requiring narcotics by postoperative day 3. Conclusion Our results support reduced opiate prescription and encouragement of nonnarcotic use after ESS without compromising effective pain management.
Due to the potentially unforgiving nature of epiglottitis and supraglottitis, the clinician should have a firm understanding of the presentation, work up, and management of a patient presenting with worrisome symptoms.
Objective The coronavirus disease 2019 (COVID-19) pandemic disrupted the standard management paradigms for care of patients with sinus and skull base presentations due to concern for patient and health care provider safety, given the high aerosol-generating potential of endonasal procedures. Data Sources We reviewed the relevant literature complied from available sources, including PubMed, Google Scholar, and otolaryngology journals providing electronic manuscripts ahead of indexing or publication. Review Methods Incorporating available evidence and the projected infection control and resource limitations at our institution, we collectively authored a dynamic set of protocols guiding (1) case stratification, (2) preoperative assessment, (3) operative setup, and (4) postoperative care of patients with sinus or skull base presentations. Due to the rapidly evolving nature of COVID-19 publications, lack of rigorous data, and urgent necessity of standardized protocols, strict inclusion and exclusion criteria were not employed. Conclusions As scarce hospital resources are diverted to COVID-19 care and staff are redeployed to forward-facing roles, endonasal procedures have largely ceased, leaving patients with ongoing sinonasal and skull base complaints untreated. Skull base teams now weigh the urgency of surgery in this population with the regional availability of resources. Implications for Practice The COVID-19 pandemic will have an enduring and unpredictable impact on hospital operations and surgical skull base practices and will require a dynamic set of management protocols responsive to new evidence and changing resources. In the current resource-limited environment, clinicians may utilize these protocols to assist with stratifying patients by acuity, performing preoperative assessment, and guiding peri- and postoperative care.
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