Expression of ETS1 and LEF1 in salivary glands of Sjögren syndrome patients.

OBJECTIVE: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease affecting exocrine glands, thereby causing dry mouth and eyes (sicca). Our objective was to determine the expression of pSS pathogenic biomarker MMP9 and its putative transcription factors ETS1 and LEF1, in labial salivary glands of pSS patients. METHODS: Sicca patients were assigned to three groups based on focus score (FS): non-pSS sicca (i.e., GR1 [FS = 0] and GR2 [0 < FS < 1]) and pSS (i.e., GR3 [FS ≥ 1]). We determined the mRNA and protein expression of MMP9, ETS1, and LEF1 in salivary gland biopsies. Also, ETS1-CD4 and LEF1-CD4 co-expression analyses were performed. RESULTS: The mRNA expression of MMP9, ETS1, and LEF1 was upregulated in GR3 compared to GR1 (p < 0.01). Most GR3 salivary gland areas had moderate to high MMP9, ETS1, and LEF1 protein expression compared to GR1 and GR2. Further, ETS1-CD4 and LEF1-CD4 dual staining demonstrated that both salivary gland epithelial cells and lymphocytic infiltrates had increased levels of ETS1 and LEF1. Moreover, there was a strong correlation between ETS1(+)-CD4(-) and LEF1(+)-CD4(-) cells. CONCLUSION: These results suggest, for the first time, a concerted increase in ETS1 and LEF1 expression in salivary gland epithelial cells of pSS patients that is reflective of the etiopathogenesis of pSS.

Swallowing dysfunction in cancer patients.

PURPOSE: Dysphagia (swallowing dysfunction) is a debilitating, depressing, and potentially life-threatening complication in cancer patients that is likely underreported. The present paper is aimed to review relevant dysphagia literature between 1990 and 2010 with a focus on assessment tools, prevalence, complications, and impact on quality of life in patients with a variety of different cancers, particularly in those treated with curative chemoradiation for head and neck cancer. METHODS: The literature search was limited to the English language and included both MEDLINE/PubMed and EMBASE. The search focused on papers reporting dysphagia as a side effect of cancer and cancer therapy. We identified relevant literature through the primary literature search and by articles identified in references. RESULTS: A wide range of assessment tools for dysphagia was identified. Dysphagia is related to a number of factors such as direct impact of the tumor, cancer resection, chemotherapy, and radiotherapy and to newer therapies such as epidermal growth factor receptor inhibitors. Concomitant oral complications such as xerostomia may exacerbate subjective dysphagia. Most literature focuses on head and neck cancer, but dysphagia is also common in other types of cancer. CONCLUSIONS: Swallowing impairment is a clinically relevant acute and long-term complication in patients with a wide variety of cancers. More prospective studies on the course of dysphagia and impact on quality of life from baseline to long-term follow-up after various treatment modalities, including targeted therapies, are needed.

A systematic review of trismus induced by cancer therapies in head and neck cancer patients.

PURPOSE: This systematic review represents a thorough evaluation of the literature to clarify the impact of cancer therapies on the prevalence, quality of life and economic impact, and management strategies for cancer-therapy-induced trismus. METHODS: A systematic literature search was conducted with assistance from a research librarian in the databases MEDLINE/PubMed and EMBASE for articles published between January 1, 1990 and December 31, 2008. Each study was independently assessed by two reviewers. Taking into account predetermined quality measures, a weighted prevalence was calculated for the prevalence of trismus. The level of evidence, recommendation grade, and guideline (if possible) were given for published preventive and management strategies for trismus. RESULTS: We reviewed a total of 22 published studies between 1990 and 2008. Most of them assessed the prevalence of this complication, and few focused on management. The weighted prevalence for trismus was 25.4% in patients who received conventional radiotherapy and 5% for the few intensity-modulated radiation therapy studies. No clear guideline recommendations could be made for the prevention or management of trismus. CONCLUSIONS: Newer radiation modalities may decrease the prevalence of trismus compared to conventional radiotherapy. Few studies have addressed the quality of life impact of trismus, and no studies were identified to assess the economic impact of trismus. The few preventive and management trials identified in the literature showed some promise, although larger, well-designed studies are required to appropriately assess these therapies before recommendations can be provided.

Unique Geospatial Accumulations of Uveal Melanoma.

PURPOSE: The main purpose of this paper was to describe the unique accumulation of cases of uveal melanoma (UM). All patients were white and did not have known occupational risk factors. From the authors' standpoint, there were no lifestyle factors in common in the reported cases. Results of more extensive analyses, including geospatial analysis, are currently being conducted and will be presented in a separate paper. DESIGN: Observational case series. METHODS: Descriptive data from medical records, patient interviews, and questionnaires were obtained from 5 patients from North Carolina, 6 patients from Alabama, and 14 patients from New York. Standard incidence ratio (SIR) calculations were provided by the respective states' cancer registries. UM is the most common primary malignant eye tumor in adults, although it is rare, with 2,500 cases diagnosed annually in the United States. Despite a growing understanding of the molecular characteristics, there remains uncertainty regarding epidemiologic trends and environmental risk factors. This study identified 3 geographic accumulations of UM: 1) Huntersville, NC; 2) Auburn, AL; and 3) Broome and Tioga Counties, New York. Investigation of these groups will guide ongoing efforts to discover potential risk factor and assist with future treatment and prevention. RESULTS: In North Carolina, 5 females who were identified as living in Huntersville, NC, were diagnosed with UM at ages 20, 22, 24, 30, and 31. The SIR calculations considering the observed and expected incidence ratios was 0.7 (95% confidence interval [CI], 0.5-0.9) in Mecklenburg County. In Alabama, 6 individuals who were identified as either attending Auburn University or employed there from 1989 to 1993 had diagnoses of UM. Initial SIR calculations for white females of all ages was 1.15 (95% CI, 0.989-1.328). In New York, SIR for Broome and Tioga counties were 0.93 and not significant. However, in Tioga county, for males and females and females alone, SIRs were 2.00 (P = .04) and 3.33 (P = .006). CONCLUSIONS: Although most of the conclusions that the SIR does not meet statistical criteria that defines these accumulations as true "cancer clusters," considering the incidence and demographics of UM, these accumulations of cases is unexpected and worth additional exploration. Further investigation into these cases with additional geospatial analyses and blood and tumor testing is ongoing. Information learned from the study of these unique populations may inform a better understanding of the pathogenesis of UM.

Prospective study of outcomes after reduction mammaplasty.

BACKGROUND: The purpose of this study was to prospectively assess changes in overall health-related quality of life and breast-related symptoms in women undergoing reduction mammaplasty, and to compare preoperative and postoperative health-related quality of life with that of the normal population. METHODS: Fifty-six patients were evaluated preoperatively and 6 months postoperatively with three questionnaires: the Short Form-36 Health Survey, the Symptom Inventory Questionnaire, and the Rosenberg Self-Esteem Scale. Surgeons completed preoperative patient assessment forms, operative note forms, and postoperative patient assessment forms. RESULTS: Comparison of preoperative and postoperative health-related quality of life showed significant improvements in Short Form-36 Health Survey scores (p < 0.005), the Rosenberg Self-Esteem Scale (p < 0.001), and all symptoms on the Symptom Inventory Questionnaire (p < 0.003). Preoperative mean Short Form-36 Health Survey scores were lower than in the normal population in several areas (p < 0.005). Postoperatively, none of the mean Short Form-36 Health Survey scores were significantly lower than population norms. CONCLUSIONS: This study determined that there is a significant improvement of physical symptoms and health-related quality of life in women undergoing reduction mammaplasty at 6 months after surgery. Before surgery, these patients have a significantly worse health-related quality of life than the normal population, but they normalize postoperatively.