Faculty Bibliography

Introduction Oral mucositis (OM) is one of the most debilitating adverse effects in patients undergoing cancer treatment. Physiologically, chemotherapy (CT) and radiotherapy (RT) evoke a profound inflammatory response, resulting in mucosal injury, which can result in an increased susceptibility to infection. Objectives The objective of this pilot study was to asses the effects of a novel oral care protocol on OM severity and to evaluate salivary cytokines in head and neck cancer patients undergoing RT or CT/RT at the NYU Langone Laura and Isaac Perlmutter Cancer Center. Methods A total of ten participants were included in this study, and randomized to an InterventionGroup (IG), or ControlGroup (CG). Subjects assigned to the CG received a standard of care oral hygiene on a bi-weekly basis. Subjects assigned to the IG received the Oral Mucosal Deterging and Dental Prophylaxis (OMDP) protocol weekly, which consisted of a periodontal surface debridement and cleansing and deterging of the oral mucosa surfaces. Results Salivary inflammatory biomarkers, noted in levels of IFN-gamma, IL10, IL12p70, IL13, TNFalpha and IL-6 had a significant increase in the CG and reduced or stayed the same under the IG. Although not statistically significant, a tendency of pain decrease was observed in the IG and difficulty in swallowing was statistically significant when both groups were compared (p = 0,016). Conclusions These results suggest that overall inflammation was consistently higher as compared to baseline in the CG, providing encouragement for the effectiveness of the oral care protocol as a coadjutant treatment for this population

A guide to medications inducing salivary gland dysfunction, xerostomia and subjective sialorrhea: A systematic review sponsored by the World Workshop on Oral Medicine VI Background – Medication-induced salivary gland dysfunction (MISGD), xerostomia (sensation of oral dryness) and subjective sialorrhea cause significant morbidity and impair quality of life. However, evidence-based lists of medications that cause these disorders do not exist. Objective – To compile a list of medications affecting salivary gland function and inducing xerostomia or subjective sialorrhea. Data Sources – Electronic databases were searched for relevant articles published until June 2013. Data Synthesis – A total of 269 papers out of a total of 3867 screened records had an acceptable degree of relevance, quality of methodology and strength of evidence. We found 56 chemical substances with higher level of evidence and 50 with a moderate level of evidence of causing the above mentioned disorders. At the first level of the Anatomical Therapeutic Chemical classification system (ATC), 9 out of 14 anatomical groups were represented, mainly the alimentary, cardiovascular, genitourinary, nervous and respiratory systems. Management strategies include substitution or discontinuation of medications whenever possible, oral or systemic therapy with sialogogues, administration of saliva substitutes, and use of electro-stimulating devices. Limitations – While xerostomia was a commonly reported outcome, objectively measured salivary flow rate was rarely reported. Moreover, xerostomia was mostly assessed as an adverse effect rather than the primary outcome of medication use. This study may not include some medications that could cause xerostomia when given in conjunction with others or for which xerostomia as an adverse reaction has not been reported in the literature or not detected in our search. Conclusions – A comprehensive list of medications having documented effects on salivary gland function or symptoms was compiled, which may assist practitioners in assessing patients who complain of dry mouth while taking medications. The list may also prove useful for anticipating adverse effects and help practitioners to consider alternative medications

BACKGROUND: Medication-induced salivary gland dysfunction (MISGD), xerostomia (sensation of oral dryness), and subjective sialorrhea cause significant morbidity and impair quality of life. However, no evidence-based lists of the medications that cause these disorders exist. OBJECTIVE: Our objective was to compile a list of medications affecting salivary gland function and inducing xerostomia or subjective sialorrhea. DATA SOURCES: Electronic databases were searched for relevant articles published until June 2013. Of 3867 screened records, 269 had an acceptable degree of relevance, quality of methodology, and strength of evidence. We found 56 chemical substances with a higher level of evidence and 50 with a moderate level of evidence of causing the above-mentioned disorders. At the first level of the Anatomical Therapeutic Chemical (ATC) classification system, 9 of 14 anatomical groups were represented, mainly the alimentary, cardiovascular, genitourinary, nervous, and respiratory systems. Management strategies include substitution or discontinuation of medications whenever possible, oral or systemic therapy with sialogogues, administration of saliva substitutes, and use of electro-stimulating devices. LIMITATIONS: While xerostomia was a commonly reported outcome, objectively measured salivary flow rate was rarely reported. Moreover, xerostomia was mostly assessed as an adverse effect rather than the primary outcome of medication use. This study may not include some medications that could cause xerostomia when administered in conjunction with others or for which xerostomia as an adverse reaction has not been reported in the literature or was not detected in our search. CONCLUSIONS: We compiled a comprehensive list of medications with documented effects on salivary gland function or symptoms that may assist practitioners in assessing patients who complain of dry mouth while taking medications. The list may also prove useful in helping practitioners anticipate adverse effects and consider alternative medications.

Oral melanoacanthoma (MA) is a rare, benign pigmented lesion that presents as a painless, rapidly growing, brown-black macular lesion that commonly affects the buccal mucosa in areas that are subject to chronic trauma/irritation.1,2 MA is commonly seen in the third and fourth decades of life and primarily affects blacks with a strong female predilection.3,4 Histopathologically, the lesions exhibit proliferation of keratinocytes and dendritic melanocytes.5 This report includes two cases of oral melanoacanthoma and a review of the literature. Case 1: A 43-year-old black female presented with a slowly enlarging pigmented lesion on the right buccal mucosa. The patient did not recall any known trauma to the area or previous infection and reported that the lesion was painless but had a gradually increased in size. Oral examination revealed a 2.0 x 2.0 cm. brown macule on the right buccal mucosa. A punch biopsy was taken of the pigmented area. The tissue was placed in 10% formalin and submitted for microscopic examination. The tissue was stained with hematoxylin and eosin and exhibited acanthotic, stratified squamous epithelium with dendritic melanocytes dispersed throughout the epithelium consistent with a diagnosis of melanoacanthoma. Case 2: A-35 year-old black female presented with a rapidly growing pigmented lesion on the left buccal mucosa. Two years prior to presentation the patient had noted a brown lesion on the buccal mucosa adjacent to a fractured tooth. The lesion remained unchanged and asymptomatic for approximately two years. One week prior to presentation, the patient noted that the lesion was enlarging, but remained painless. Oral examination revealed a 1.5 x 1.5 cm. brown macule surrounded by erythema on the left buccal mucosa adjacent to a fractured tooth. A punch biopsy was taken that included both the pigmented and erythematous areas. The tissue was placed in 10% formalin and submitted for microscopic examination. The tissue was stained with hematoxylin and eosin and exhibited similar histopathologic features to the previous case. Immunohistochemical staining with S-100 and Melan-A dramatically demonstrated the dendritic melanocytes. Review of the literature revealed a total of 50 cases of oral melanoacanthoma. These lesions were reported in black females on the buccal mucosa with subsequent resolution. The cases here demonstrate similar clinical features and age at presentation to previously reported cases. The pathogenesis of oral MA remains unclear, however, most studies suggest this is a reactive process due to chronic irritation.2 Oral MA may regress following biopsy and no surgical intervention is required due to its selfresolving quality.5

Despite significant advances in surgical procedures and treatment, long-term prognosis for patients with oral cancer remains poor, with survival rates among the lowest of major cancers. Better methods are desperately needed to identify potential malignancies early when treatments are more effective. OBJECTIVE: To develop robust classification models from cytology-on-a-chip measurements that mirror diagnostic performance of gold standard approach involving tissue biopsy. MATERIALS AND METHODS: Measurements were recorded from 714 prospectively recruited patients with suspicious lesions across 6 diagnostic categories (each confirmed by tissue biopsy -histopathology) using a powerful new 'cytology-on-a-chip' approach capable of executing high content analysis at a single cell level. Over 200 cellular features related to biomarker expression, nuclear parameters and cellular morphology were recorded per cell. By cataloging an average of 2000 cells per patient, these efforts resulted in nearly 13 million indexed objects. RESULTS: Binary "low-risk"/"high-risk" models yielded AUC values of 0.88 and 0.84 for training and validation models, respectively, with an accompanying difference in sensitivity+specificity of 6.2%. In terms of accuracy, this model accurately predicted the correct diagnosis approximately 70% of the time, compared to the 69% initial agreement rate of the pool of expert pathologists. Key parameters identified in these models included cell circularity, Ki67 and EGFR expression, nuclear-cytoplasmic ratio, nuclear area, and cell area. CONCLUSIONS: This chip-based approach yields objective data that can be leveraged for diagnosis and management of patients with PMOL as well as uncovering new molecular-level insights behind cytological differences across the OED spectrum.