Faculty Bibliography

Purpose: Non-tuberculous mycobacteria (NTM) is an intracellular microorganism that causes cavitary disease and nodular bronchiectatic disease of the lung. Common symptoms include chronic cough, sputum production and frequent pneumonias. Patients with NTM appear to have impaired swallow function as represented by impaired airway protection. Our aim is to determine bolus clearance in patients with NTM compared with a control. Method(s): Videofluoroscopy (VF) was prospectively collected from 195 patients:132 patients with NTM (90 females; ages 30-90) and 63 age-and sex-matched normal controls with normal pulmonary function tests and no pulmonary disease (39 females; ages 27-92).Two boluses of 3, 5, 10 mL thin liquid, two 5 mL puree Varibar, and cracker were analyzed per subject (N = 1,755 swallows).Outcome measures included ordinal ratings of residue in the valleculae and pyriform sinuses. The correlation between clinical information and the present of pharyngeal residue structures was analyzed by Fisher's exact test for categorical variables and Wilcoxon's rank sum test for comparisons of continuous variables between groups. Result(s): Inter-and intra-rater reliability of the ordinal ratings were assessed using two-way random intraclass correlation coefficients (ICC(2,1)) on 20% of the data with good results (intra-rater: ICC = 0.92, 95% CI 0.70-0.97 and inter-rater: ICC = 0.92, 95% CI 0.81-0.97).The ratings of residue in the valleculae were significantly higher in the NTM group compared to the control group for one of the 3 mL bolus (p = 0.008), for 5 mL boluses (p = 0.009 and p = 0.004), 10 mL boluses (p = 0.0005 and p = 0.0006), puree (p = 0.006), cracker (p = 0.005).The ratings of residue in the pyriform sinuses were also significantly higher in the NTM group for 3 mL boluses (p = 0.0002 and p = 0.01), 5 mL boluses (p = 0.0003 and p = 0.002), 10 mL boluses (p = 0.001 and p = 0.001), puree trials (p<0.0001 and p<0.0001).Wilcoxon's rank sum test determined no age difference and Fisher's exact test determined no gender difference between the NTM and control groups. Conclusions (Including Clinical Relevance): Patients with NTM appear to have reduced bolus clearance than healthy individuals with no pulmonary disease, as represented by ratings of residue in the valleculae and pyriform sinuses.Future work is needed to elucidate the interaction between the respiratory-swallowing systems and airway protection and responsiveness to swallowing treatment for patients with NTM

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

Early detection of oral cancer necessitates a minimally invasive, tissue-specific diagnostic tool that facilitates screening/surveillance. Brush biopsy, though minimally invasive, demands skilled cyto-pathologist expertise. In this study, we explored the clinical utility/efficacy of a tele-cytology system in combination with Artificial Neural Network (ANN) based risk-stratification model for early detection of oral potentially malignant (OPML)/malignant lesion. A portable, automated tablet-based tele-cytology platform capable of digitization of cytology slides was evaluated for its efficacy in the detection of OPML/malignant lesions (n = 82) in comparison with conventional cytology and histology. Then, an image pre-processing algorithm was established to segregate cells, ANN was trained with images (n = 11,981) and a risk-stratification model developed. The specificity, sensitivity and accuracy of platform/ stratification model were computed, and agreement was examined using Kappa statistics. The tele-cytology platform, Cellscope, showed an overall accuracy of 84-86% with no difference between tele-cytology and conventional cytology in detection of oral lesions (kappa, 0.67-0.72). However, OPML could be detected with low sensitivity (18%) in accordance with the limitations of conventional cytology. The integration of image processing and development of an ANN-based risk stratification model improved the detection sensitivity of malignant lesions (93%) and high grade OPML (73%), thereby increasing the overall accuracy by 30%. Tele-cytology integrated with the risk stratification model, a novel strategy established in this study, can be an invaluable Point-of-Care (PoC) tool for early detection/screening in oral cancer. This study hence establishes the applicability of tele-cytology for accurate, remote diagnosis and use of automated ANN-based analysis in improving its efficacy.

Oral cancer patients report severe function-induced pain; severity is greater in females. We hypothesize that a neutrophil-mediated endogenous analgesic mechanism is responsible for sex differences in nociception secondary to oral squamous cell carcinoma (SCC). Neutrophils isolated from the cancer-induced inflammatory microenvironment contain β-endorphin protein and are identified by the Ly6G⁺ immune marker. We previously demonstrated that male mice with carcinogen-induced oral SCC exhibit less nociceptive behavior and a higher concentration of neutrophils in the cancer microenvironment compared to female mice with oral SCC. Oral cancer cells secrete granulocyte colony stimulating factor (G-CSF), a growth factor that recruits neutrophils from bone marrow to the cancer microenvironment. We found that recombinant G-CSF (rG-CSF, 5 μg/mouse, intraperitoneal) significantly increased circulating Ly6G⁺ neutrophils in the blood of male and female mice within 24 h of administration. In an oral cancer supernatant mouse model, rG-CSF treatment increased cancer-recruited Ly6G⁺ neutrophil infiltration and abolished orofacial nociceptive behavior evoked in response to oral cancer supernatant in both male and female mice. Local naloxone treatment restored the cancer mediator-induced nociceptive behavior. We infer that rG-CSF-induced Ly6G⁺ neutrophils drive an endogenous analgesic mechanism. We then evaluated the efficacy of chronic rG-CSF administration to attenuate oral cancer-induced nociception using a tongue xenograft cancer model with the HSC-3 human oral cancer cell line. Saline-treated male mice with HSC-3 tumors exhibited less oral cancer-induced nociceptive behavior and had more β-endorphin protein in the cancer microenvironment than saline-treated female mice with HSC-3 tumors. Chronic rG-CSF treatment (2.5 μg/mouse, every 72 h) increased the HSC-3 recruited Ly6G⁺ neutrophils, increased β-endorphin protein content in the tongue and attenuated nociceptive behavior in female mice with HSC-3 tumors. From these data, we conclude that neutrophil-mediated endogenous opioids warrant further investigation as a potential strategy for oral cancer pain treatment.