Faculty Bibliography

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BACKGROUND:Lymph node yield (LNY) is a proposed quality indicator in neck dissection for oral cavity squamous cell carcinoma (OCSCC). METHODS:Retrospective series including 190 patients with OCSCC undergoing neck dissection between 2016 and 2018. A change in pathologic grossing protocol was initiated during the study period to assess residual adipose tissue. A generalized linear model was used to assess the impact of multiple variables on LNY. RESULTS:Mean LNY was 28.59 (SD = 17.65). The protocol identified a mean of 10.32 lymph nodes per case. Multivariable analysis identified associations between LNY and use of the pathology protocol (P = .02), number of dissected lymph node levels (P < .001), presence of pathologic lymph nodes (P = .002), body mass index (P = .02), prior neck surgery (P = .001), and prior neck radiation (P = .001). CONCLUSIONS:Assessment of residual adipose tissue within neck dissection specimens improves accuracy of LNY. LNY in neck dissection is influenced by multiple factors including methods of pathologic assessment.

OBJECTIVE:The aim of this study was to assess the influence of clinical cues on risk assessment of cancer-associated mucosal abnormalities. STUDY DESIGN/METHODS:We differentiated lesions with a low risk from those with a high risk for premalignancy or malignancy by using 4 cues: (1) color, (2) location, (3) induration, and (4) pain on exploration. Combinations of color and location were presented through 8 photographs, with induration and pain status variably presented in the standardized history and physical findings. This created 16 clinical scenarios (vignettes) that were permutations of the 4 cues. Three questions assessed the extent to which each cue was used in obtaining a clinical impression as to whether a lesion was benign, premalignant, or malignant. RESULTS:Completed vignette questionnaires were obtained from 130 of 228 invited dentists, (two-thirds males; 79% white; mean age 52 years; average weekly hours of practice 33 hours). Only 40% of the responding dentists had statistically significant decision policies to assign a clinical diagnosis of a lesion as benign, premalignant, or malignant. Lesion location and color were the 2 dominant cues. As a cue, induration was used as a cue by more of the respondents in determining a clinical diagnosis of malignancy, and pain was infrequently used as a cue. CONCLUSIONS:Many dentists do not to have a decision strategy for the clinical diagnosis and risk stratification of oral potentially malignant lesions.

OBJECTIVE:To determine risk factors for readmission, prolonged length of stay, and discharge to a rehabilitation facility in patients with acute mastoiditis. Trends in treatment and complication rates were also examined. STUDY DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:Nationwide Readmissions Database (2013, 2014). PATIENTS/METHODS:Pediatric and adult patients in the Nationwide Readmissions Database with a primary diagnosis of acute mastoiditis. INTERVENTIONS/METHODS:Medical treatment, surgical intervention. OUTCOME MEASURES/METHODS:Rates of and risk factors for readmission, prolonged length of stay, and discharge to a rehabilitation facility. Procedure and complication rates were also examined. RESULTS:Four thousand two hundred ninety-five pediatric and adult admissions for acute mastoiditis were analyzed. The overall rates of readmission, prolonged length of stay, and discharge to a rehabilitation facility were 17.0, 10.4, and 10.2%, respectively. Children 4 to 17 years of age had the highest rates of intracranial complications, and children ≤3 years were most likely to undergo operative intervention. Any procedure was performed in 31.2% of cases, and undergoing myringotomy or mastoidectomy was associated with lower rates of readmission but higher rates of prolonged length of stay. Those with intracranial complications and subperiosteal abscesses had the highest surgical intervention rates. CONCLUSIONS:Readmission, prolonged length of stay, and discharge to a rehabilitation facility are common in patients with acute mastoiditis with various sociodemographic and disease-related risk factors. While once a primarily surgical disease, a minority of patients in our cohort underwent procedures. Undergoing a surgical procedure was protective against readmission but a risk factor for prolonged length of stay.

Migraine is commonly reported among patients with temporomandibular disorders (TMDs), especially myogenic TMD. The pathophysiologic mechanisms related to the comorbidity of the two conditions remain elusive. In the present study, we combined masseter muscle tendon ligation (MMTL)-produced myogenic TMD with systemic injection of nitroglycerin (NTG)-induced migraine-like hypersensitivity in mice. Facial mechanical allodynia, functional allodynia, and light-aversive behavior were evaluated. Sumatriptan, an FDA-approved medication for migraine, was used to validate migraine-like hypersensitivity. Additionally, we examined the protein level of calcitonin gene-related peptide (CGRP) in the spinal trigeminal nucleus caudalis using immunohistochemistry. We observed that mice with MMTL pretreatment have a prolonged NTG-induced migraine-like hypersensitivity, and MMTL also enabled a non-sensitizing dose of NTG to trigger migraine-like hypersensitivity. Systemic injection of sumatriptan inhibited the MMTL-enhanced migraine-like hypersensitivity. MMTL pretreatment significantly upregulated the protein level of CGRP in the spinal trigeminal nucleus caudalis after NTG injection. Our results indicate that a pre-existing myogenic TMD can upregulate NTG-induced trigeminal CGRP and enhance migraine-like hypersensitivity.

Whether G protein-coupled receptors signal from endosomes to control important pathophysiological processes and are therapeutic targets is uncertain. We report that opioids from the inflamed colon activate δ-opioid receptors (DOPr) in endosomes of nociceptors. Biopsy samples of inflamed colonic mucosa from patients and mice with colitis released opioids that activated DOPr on nociceptors to cause a sustained decrease in excitability. DOPr agonists inhibited mechanically sensitive colonic nociceptors. DOPr endocytosis and endosomal signaling by protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) pathways mediated the sustained inhibitory actions of endogenous opioids and DOPr agonists. DOPr agonists stimulated the recruitment of Gα_i/o and β-arrestin1/2 to endosomes. Analysis of compartmentalized signaling revealed a requirement of DOPr endocytosis for activation of PKC at the plasma membrane and in the cytosol and ERK in the nucleus. We explored a nanoparticle delivery strategy to evaluate whether endosomal DOPr might be a therapeutic target for pain. The DOPr agonist DADLE was coupled to a liposome shell for targeting DOPr-positive nociceptors and incorporated into a mesoporous silica core for release in the acidic and reducing endosomal environment. Nanoparticles activated DOPr at the plasma membrane, were preferentially endocytosed by DOPr-expressing cells, and were delivered to DOPr-positive early endosomes. Nanoparticles caused a long-lasting activation of DOPr in endosomes, which provided sustained inhibition of nociceptor excitability and relief from inflammatory pain. Conversely, nanoparticles containing a DOPr antagonist abolished the sustained inhibitory effects of DADLE. Thus, DOPr in endosomes is an endogenous mechanism and a therapeutic target for relief from chronic inflammatory pain.

BACKGROUND:Complications from radiotherapy (RT) alone or combined with surgery and/or chemotherapy for head and neck cancer (HNC) sometimes necessitate hospitalization. Our aim was to evaluate the frequency, cause, and survival outcomes associated with hospitalizations in patients undergoing RT for HNC. PATIENTS AND METHODS/METHODS:Using a retrospective single-institution database, we reviewed hospitalization records of HNC patients treated at Roswell Park Comprehensive Cancer Center with definitive or post-operative RT between 2003 and 2017. Patients who were admitted during treatment and within 90-days post-RT were identified. Multivariate analyses, Kaplan-Meier statistics, and analysis on propensity score matching were performed to obtain matched-pair, after matching baseline characteristics, such as age, gender, smoking, tumor staging, p16 status, and treatments received. RESULTS:839 patients were eligible for analysis. Median follow-up was 34.8 months (Interquartile range [IQR] 15.6-64.8). 595 (71%) received definitive RT and 244 (29%) received adjuvant RT. Chemotherapy was used in 671 patients (80%). 171 patients (20%) had at least one hospitalization. Dehydration (40%) and fever (29%) were the most frequent causes of admission. Hospitalized patients had significantly worse overall survival (OS) (Hazards ratio [HR] 1.61, 95% CI 1.26-2.07, p < 0.001) and cancer-specific survival (CSS) (HR 1.45, 95% CI 1.07-1.95, p = 0.02). 163 matched pairs had median follow-up of 58.6 months (IQR 37.6-85.0). Median OS was 34.5 months (IQR 13.3-58.0) for hospitalized versus 44.2 months (IQR 20.3-78.7) for non-hospitalized patients (p = 0.01). CONCLUSION/CONCLUSIONS:This study reveals significantly worse OS and CSS for patients hospitalized during RT for HNC. Hospitalization may be an early marker for worse survival.

The reconstruction of full thickness scalp defects following oncologic resection poses a unique challenge that is further magnified in "extremely elderly" patients, defined as those in at least their ninth decade of life, who are often unsuitable candidates for complex reconstruction. A "simpler" option is two-stage reconstruction: placement of Integra dermal regenerative template (Integra Life Science, Plainsboro, NJ) followed by a split thickness skin graft (STSG). This case series illustrates the success of this technique in the extremely elderly. A retrospective analysis of patients > 80 years at the time of surgery who underwent full thickness scalp reconstruction following tumor extirpation in a two-stage approach under the care of single surgeon from January 2010 to June 2019 was conducted. Variables reviewed were medical history, surgical treatment response, time to split thickness skin graft, follow up, and success of wound coverage. Fourteen patients, with a mean age of 87 years (range: 80 to 101, median: 87), met inclusion criteria. Split thickness skin grafts were placed after an average of 18 days. Twelve patients had successful two-stage reconstruction with 100% take. One patient developed a hematoma under a portion of the template that neither required reoperation nor delayed split thickness skin graft placement. A second suffered from insufficient vascularization of the template with delay to split thickness skin graft and incomplete wound closure. This two-stage approach is a successful primary reconstructive option for definitive management of full thickness scalp defects following oncologic resection in extremely elderly patients.