Faculty Bibliography

PURPOSE: Surgical resection of midface neoplasms and subsequent reconstruction have been shown to have significant negative effects on quality of life (QOL). The purpose of this pilot study was to assess individuals' health-related QOL after maxillectomy and reconstruction with a prosthetic obturator. MATERIALS AND METHODS: The QOL of 25 of 43 patients who underwent maxillectomy and prosthetic obturator reconstruction at the University of California-San Francisco was assessed using 3 questionnaires: University of Washington Quality of Life version 4 (UWQOL), Obturator Functioning Scale (OFS), and Mental Health Inventory (MHI). RESULTS: The response rate to the QOL questionnaires was 92% (23 of 25 patients). Time elapsed from maxillectomy and prosthetic obturator reconstruction to the QOL survey response ranged from 0.3 to 6.6 years (mean, 2.7 years; standard deviation [SD], 1.9 years). The post-treatment mean QOL scores were 77.3 (SD, 13.6) for UWQOL, 72.0 (SD, 12.6) for OFS, and 4.5 (SD, 0.9) for Mental Health Inventory. Individuals who received adjuvant radiation scored lower for speech and appearance (OFS, P = .05, P = .03, respectively) as well as for saliva and overall QOL (UWQOL, P = .02, P = .08, respectively). There was a strong correlation between QOL scores in OFS and UWQOL questionnaires (r = 0.78, P < .001). CONCLUSION: The results of this pilot study suggest that postoperative radiation therapy was the strongest variable affecting QOL in patients with maxillectomy and prosthetic obturator reconstruction. There is further need for a multicenter trial with a larger sample to identify how factors affecting QOL of patients after maxillectomy might influence the choice of reconstruction.

Cisplatin is the primary chemotherapy for head and neck squamous cell carcinoma (HNSCC). No equally effective chemotherapeutics are available when cisplatin resistance occurs. We hypothesize that DNA methylation of key genes mediates cisplatin resistance; moreover, pretreatment with decitabine, a demethylating agent, restores cisplatin sensitivity by mediating expression of genes that are instrumental to cisplatin resistance. Objectives: 1) Determine whether decitabine treatment of a cisplatin-resistant HNSCC cell line restores the anti-proliferative and apoptotic effects of cisplatin; 2) Evaluate the anti-proliferative effect of decitabine and cisplatin (i.e. combination treatment) on a preclinical HNSCC model; 3) Determine whether combination treatment reduces cancer pain; and 4) Create a "gene expression profile of cisplatin resistance" by analyzing cisplatinsensitive and cisplatin-resistant HNSCC in patients. Methods: SCC-25, a cisplatin-sensitive HNSCC cell line, and SCC-25/CP, a cisplatin-resistant cell line, were pre-treated with 5mM decitabine and then treated with cisplatin (3-300 mM) for 48 hours. Proliferation was quantified with an MTS assay. Apoptosis was quantified with a caspase 3/7 assay. A preclinical model was created by inoculating SCC-25/CP cells into the hind-paw of BALB/ c mice. Twenty-four mice were placed into one of four treatment groups: control sham, decitabine-only, cisplatin- only, or combination treatment. Decitabine (6 mg/kg) was administered on post-inoculation days (PID) seven and nine, and cisplatin (6 mg/kg) was administered on PID 12, 15, 18, and 21. Tumor growth was quantified. Mechanical allodynia (i.e. pain) was quantified with a paw withdrawal assay. Formalin-fixed, paraffin- embedded biopsies were obtained from HNSCC patients who underwent chemotherapy with cisplatin. Tumors were classified as either cisplatin-sensitive (RECIST 3 or 4) or cisplatin-resistant (RECIST 1 or 2). Gene expression was quantified in these two sets of samples. Results: In the in !

The purposes of this study were to evaluate for differences in phenotypic and genotypic characteristics in women who did and did not develop lymphedema (LE) following breast cancer treatment. Breast cancer patients completed a number of self-report questionnaires. LE was evaluated using bioimpedance spectroscopy. Genotyping was done using a custom genotyping array. No differences were found between patients with (n = 155) and without LE (n = 387) for the majority of the demographic and clinical characteristics. Patients with LE had a significantly higher body mass index, more advanced disease and a higher number of lymph nodes removed. Genetic associations were identified for four genes (i.e., lymphocyte cytosolic protein 2 (rs315721), neuropilin-2 (rs849530), protein tyrosine kinase (rs158689), vascular cell adhesion molecule 1 (rs3176861)) and three haplotypes (i.e., Forkhead box protein C2 (haplotype A03), neuropilin-2 (haplotype F03), vascular endothelial growth factor-C (haplotype B03)) involved in lymphangiogensis and angiogenesis. These genetic associations suggest a role for a number of lymphatic and angiogenic genes in the development of LE following breast cancer treatment.

Two supplements were awarded to the New York University Health Sciences Libraries from the National Library of Medicine's informationist grant program. These supplements funded research support in a number of areas, including data management and bioinformatics, two fields that the library had recently begun to explore. As such, the supplements were of particular value to the library as a testing ground for these newer services. This paper will discuss a supplement received in support of a grant from the National Institute of Dental and Craniofacial Research (PI: Brian Schmidt) on the role of proteases and peptides in cancer pain. A number of barriers were preventing the research team from maximizing the efficiency and effectiveness of their work. A critical component of the research was to identify which proteins, from among hundreds identified in collected samples, to include in preclinical testing. This selection involved laborious and prohibitively time-consuming manual searching of the literature on protein function. Additionally, the research team encompassed ten investigators working in two different cities, which led to issues around the sharing and tracking of both data and citations. The supplement outlined three areas in which the informationists would assist the researchers in overcoming these barriers: 1) creating an automated literature searching system for protein function discovery, 2) introducing tools and associated workflows for sharing citations, and 3) introducing tools and workflows for sharing data and specimens

Because multiple symptoms associated with "sickness behavior" have a negative impact on functional status and quality of life, increased information on the mechanisms that underlie inter-individual variability in this symptom experience is needed. The purposes of this study were to determine: if distinct classes of individuals could be identified based on their experience with pain, fatigue, sleep disturbance, and depression; if these classes differed on demographic and clinical characteristics; and if variations in pro- and anti- inflammatory cytokine genes were associated with latent class membership. Self-report measures of pain, fatigue, sleep disturbance, and depression were completed by 168 oncology outpatients and 85 family caregivers (FCs). Using latent class profile analysis (LCPA), three relatively distinct classes were identified: those who reported low depression and low pain (83%), those who reported high depression and low pain (4.7%), and those who reported high levels of all four symptoms (12.3%). The minor allele of IL4 rs2243248 was associated with membership in the "All high" class along with younger age, being White, being a patient (versus a FC), having a lower functional status score, and having a higher number of comorbid conditions. Findings suggest that LPCA can be used to differentiate distinct phenotypes based on a symptom cluster associated with sickness behavior. Identification of distinct phenotypes provides new evidence for the role of IL4 in the modulation of a sickness behavior symptom cluster in oncology patients and their FCs.

Background: Diagnosis and management of squamous cell carcinoma of head and neck (SCCHN) involves a multidisciplinary approach. Navigation at a public hospital can be difficult and lead to delays. In a previous study, we reported English-speaking and employed patients having longer provider delays (Lai 2011). In July 2010, we instituted the use of patient navigators, bimonthly management conferences, and improved inter-disciplinary communication in order to improve the patient experience. Aims: 1. Study differences in "provider delay" (time between first contact with health care provider and positive biopsy) between patients in cohort A (diagnosed between 1/2007 and 6/2010) and cohort "B" (diagnosed between 7/2010 and 6/ 2011). 2. Study differences in "treatment delay" (time between biopsy and initiation of treatment) between the two cohorts. 3. Determine what factors influence delays in both cohorts. Methods: The delays of the two cohorts were compared using the student t-test. Independent t-test and chi-square tests were used to examine associations between delays and the following characteristics: language, employment, presence of partner, gender, ethnicity, age, cancer sub-site, staging, number of co-morbidities, tobacco use, and alcohol use. The likelihood ratio test was used for multivariate analysis. Results: 133 patients in cohort A and 20 patients in cohort B were evaluable. Both provider and treatment delays in cohort B (50.5 and 39.3 days, respectively) were shorter than cohort A (60.2 and 41.6 days), but this was not statistically significant. The standard deviations of both delays were lower in cohort B, pointing towards a greater consistency in this group. In cohort A, provider delay was significantly shorter (p-value=0.003) for non-English speakers than English speakers on univariate and multivariate analysis. Other trends were not observed. Conclusions: Simple interventions can reduce provider and treatment delays. Our observations suggest that these interventions can mitigate t!