Faculty Bibliography

OBJECTIVES:Sentinel lymph node biopsy (SLNB) has been shown to be an accurate technique for staging the neck in early-stage oral cavity squamous cell carcinoma (OCSCC) and has been incorporated in treatment guidelines as an option instead of elective neck dissection (END). However, utilization of SLNB in the United States remains unclear, and existing prospective studies did not directly compare survival between SLNB and END. METHODS:We conducted a retrospective cohort study of patients with stage I to II OCSCC (cT1-2cN0cM0) who underwent staging of the neck in the National Cancer Data Base from 2012 to 2015. We compared the practice patterns and outcomes of patients who underwent SLNB versus END. RESULTS:We identified 8,328 eligible patients with a median follow-up of 35.4 months. SLNB was used for 240 patients, or 2.9% of stage I to II OCSCC. Completion neck dissection was avoided in 63.8% of patients undergoing SLNB. SLNB was associated with reduced perioperative morbidity, with median length of hospital stay of 1.0 days versus 3.0 days after END (P < 0.001). Perioperative 30-day mortality was 0% after SLNB versus 0.7% after END (P = 0.42). Overall 3-year survival was 82.0% after SLNB and 77.5% after END (P = 0.40). After adjustment, overall survival was equivalent between patients who underwent SLNB versus END (adjusted hazard ratio 1.03, confidence interval 0.67-1.59). CONCLUSIONS:SLNB for stage I to II OCSCC is associated with reduced length of hospital stay and equivalent overall survival compared with END. Despite these attributes, SLNB remains rarely used in the United States. LEVEL OF EVIDENCE:NA Laryngoscope, 129:162-169, 2019.

BACKGROUND:A major concern of patients who have stereotactic radiosurgery is the long-term risk of having a secondary intracranial malignancy or, in the case of patients with benign tumours treated with the technique, the risk of malignant transformation. The incidence of stereotactic radiosurgery-associated intracranial malignancy remains unknown; therefore, our aim was to estimate it in a population-based study to assess the long-term safety of this technique. METHODS:We did a population-based, multicentre, cohort study at five international radiosurgery centres (Na Homolce Hospital, Prague, Czech Republic [n=2655 patients]; Ruber International Hospital, Madrid, Spain [n=1080], University of Pittsburgh Medical Center, Pittsburgh, PA, USA [n=1027]; University of Virginia, Charlottesville, VA, USA [n=80]; and NYU Langone Health System, New York, NY, USA [n=63]). Eligible patients were of any age, and had Gamma Knife radiosurgery for arteriovenous malformation, trigeminal neuralgia, or benign intracranial tumours, which included vestibular or other benign schwannomas, WHO grade 1 meningiomas, pituitary adenomas, and haemangioblastoma. Patients were excluded if they had previously had radiotherapy or did not have a minimum follow-up time of 5 years. The primary objective of the study was to estimate the incidence of stereotactic radiosurgery-associated intracranial malignancy, including malignant transformation of a benign lesion or development of radiation-associated secondary intracranial cancer, defined as within the 2 Gy isodose line. Estimates of age-adjusted incidence of primary CNS malignancies in the USA and European countries were retrieved from the Central Brain Tumor Registry of the United States (CBTRUS) and the International Agency for Research on Cancer (IARC) Global Cancer statistics. FINDINGS/RESULTS:Of 14 168 patients who had Gamma Knife stereotactic radiosurgery between Aug 14, 1987, and Dec 31, 2011, in the five contributing centres, 4905 patients were eligible for the analysis (had a minimum follow-up of 5 years and no history of previous radiation therapy). Diagnostic entities included vestibular schwannomas (1011 [20·6%] of 4905 patients), meningiomas (1490 [30·4%]), arteriovenous malformations (1089 [22·2%]), trigeminal neuralgia (565 [11·5%]), pituitary adenomas (641 [13·1%]), haemangioblastoma (29 [0·6%]), and other schwannomas (80 [1·6%]). With a median follow-up of 8·1 years (IQR 6·0-10·6), two (0·0006%) of 3251 patients with benign tumours were diagnosed with suspected malignant transformation and one (0·0002%) of 4905 patients was considered a case of radiosurgery-associated intracranial malignancy, resulting in an incidence of 6·87 per 100 000 patient-years (95% CI 1·15-22·71) for malignant transformation and 2·26 per 100 000 patient-years (0·11-11·17) for radiosurgery-associated intracranial malignancy. Two (0·0004%) of 4905 patients developed intracranial malignancies, which were judged unrelated to the radiation field. Overall incidence of radiosurgery-associated malignancy was 6·80 per 100 000 patients-years (95% CI 1·73-18·50), or a cumulative incidence of 0·00045% over 10 years (95% CI 0·00-0·0034). The overall incidence of 6·8 per 100 000, which includes institutions from Europe and the USA, after stereotactic radiosurgery was found to be similar to the risk of developing a malignant CNS tumour in the general population of the USA and some European countries as estimated by the CBTRUS and IARC data, respectively. INTERPRETATION/CONCLUSIONS:These data show that the estimated risk of an intracranial secondary malignancy or malignant transformation of a benign tumour in patients treated with stereotactic radiosurgery remains low at long-term follow-up, and is similar to the risk of the general population to have a primary CNS tumour. Although prospective cohort studies with longer follow-up are warranted to support the results of this study, the available evidence suggests the long-term safety of stereotactic radiosurgery and could support physicians counselling patients on Gamma Knife stereotactic radiosurgery. FUNDING/BACKGROUND:None.

Previous studies have shown that tumor necrosis factor alpha (TNFα) is significantly increased in complete Freund's adjuvant (CFA)-treated temporomandibular joint (TMJ) tissues. However, it is unclear whether TNFα in the trigeminal nociceptive system contributes to the development of TMJ pain. In the present study, we investigated the role of TNFα in trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) in CFA-induced inflammatory TMJ pain. Intra-TMJ injection of CFA (10 μl, 5 mg/ml) induced inflammatory pain in the trigeminal nerve V2- and V3-innervated skin areas of WT mice, which was present on day 1 after CFA and persisted for at least 10 days. TNFα in both TG and Sp5C of WT mice was upregulated after CFA injection. The CFA-induced TMJ pain was significantly inhibited in TNFα KO mice. The immunofluorescence staining showed that intra-TMJ CFA injection not only enhanced co-localization of TNFα with Iba1 (a marker for microglia) in both TG and Sp5C but also markedly increased the expression of TNFα in the Sp5C neurons. By the methylated DNA immunoprecipitation assay, we also found that DNA methylation at the TNF gene promoter region in the TG was dramatically diminished after CFA injection, indicating that epigenetic regulation may be involved in the CFA-enhanced TNFα expression in our model. Our results suggest that TNFα in the trigeminal nociceptive system plays a critical role in CFA-induced inflammatory TMJ pain.

Introduction: Videofluoroscopic swallow studies (VFSS) are commonly requested by otolaryngologists to evaluate swallow function in patients with cough but no data exists on the utility of VFSS in this population. We aim to determine which history clinical exam and laryngoscopy findings correlate with abnormal VFSS findings in patients with cough.
Material(s) and Method(s): Ten items from flexible videolaryngoscopy were recorded including: motion abnormalities pooling of secretions pharyngeal asymmetry and glottal insufficiency. VFSS findings recorded included penetration aspiration delayed initiation and presence of residue after swallow. Nonparametric statistical analysis was performed to determine correlations between history and clinical exam observation and VFSS findings. A total of 405 patients with a chief complaint of cough were referred to speech language pathology. Of those 107 had a VFSS and 93 had an esophagram. Forty-five patients had a VFSS after referral and were included in the analysis.
Result(s): Age (p = 0.35) glottal insufficiency (p = 0.33) pooling of secretions (p = 0.10) any videolaryngoscopy abnormality (p = 0.07) cardiopulmonary history (p = 0.29) and other variables did not correlate VFSS abnormalities in patients with cough. Only gender (p = 0.02) was a predictor of an abnormal VFSS (86% males and 57% females).
Conclusion(s): This study found that videolaryngoscopy and clinical exam were not predictive of VFSS abnormalities in patients with cough

Introduction: Edema is a frequent clinical observation after chemoradiation treatment (CRT) for oral/oropharyngeal cancer (O/OP Ca). Our aims were to reliably quantify edema from video fluoroscopy (VF) at 3 time points (baseline 1-month (mo) and 4-mo post CRT) and to explore the relationship between edema and (a) patient-reported outcomes (EAT-10) and (b) functional impairment on VF (Dynamic Imaging Grade of Swallowing Toxicity DIGEST).
Material(s) and Method(s): 15 patients (7 M; age 38-76) with O/OP Ca received radiotherapy (70 Gy 7 weeks) and 3 weekly doses of cisplatin. VF was completed pre-CRT 1-mo and 4-mo post-CRT. Edema was captured by measuring posterior pharyngeal wall (PPW) thickness and pharyngeal area (PA) at rest. EAT-10 surveys were completed on the day of VF. DIGEST scores were rated according to published protocols. Mixed model repeated measures ANOVAs were run for each edema measure (PPW PA) to test for the effect of TIME EAT-10 and DIGEST while controlling for age and sex.
Result(s): For PPW we found a main effect of TIME but not EAT-10 or DIGEST (Table 1). Post-hoc comparisons revealed a significant worsening from mean at baseline (4.1 mm) to 4-mo post CRT (6.0 mm) but not at 1-mo post CRT (5.4 mm). For PA we found a main effect of TIME and of DIGEST grade (Table 2). Mean PA was significantly smaller at 1-mo post CRT (527 mm2) compared with baseline (716 mm2) but not different from 4-mo post CRT (652 mm2). Mean PA was significantly greater for grade 2 (751 mm2) compared with grade 0 (442 mm2) contrary to the hypothesized direction.
Conclusion(s): The data confirm that post-CRT edema can be quantified on 2D lateral VF. Patient reported outcomes (EAT-10) were not independently predictive of edema. Surprisingly worse DIGEST grades were associated with increased pharyngeal area at rest perhaps reflecting impairment associated with pharyngeal atrophy not edema. Future work should monitor patients' edema and swallow function over a longer time period and at a greater frequency