Anna Vlahiotis

Changing Epidemiology of Small-Cell Lung Cancer in the United States Over the Last 30 Years: Analysis of the Surveillance, Epidemiologic, and End Results Database

PURPOSE Small-cell lung cancer (SCLC) is a histologic subtype of lung cancer with a distinct biology and clinical course. It has been observed that the incidence of SCLC has been decreasing over the last several years. METHODS We used the Surveillance, Epidemiologic, and End Results (SEER) database to determine the incidence of SCLC over the last 30 years. In addition, we sought to determine sex- and stage-based differences in the incidence and survival of SCLC among a proportion of reported cases of lung cancer over the last 30 years (1973 to 2002). Joinpoint analyses were applied to test the trends in annual percentage change for statistical significance. RESULTS The proportion of SCLC (among all lung cancer histologic types) decreased from 17.26% in 1986 to 12.95% in 2002. Of all patients with SCLC, the proportion of women with SCLC increased from 28% in 1973% to 50% in 2002. A modest but statistically significant improvement in 2- and 5-year survival was noted among both limited-stage SCLC and extensive-stage SCLC cohorts during the study period. CONCLUSION Our analysis indicates that the incidence of SCLC is decreasing in the United States, and only modest improvements have been seen in survival over the last 30 years. Possible explanations for the decreasing incidence include the decrease in the percentage of smokers and the change to low-tar filter cigarettes. Despite trends toward modest improvement in survival, the outcome remains very poor.

HLA alleles determine differences in human natural killer cell responsiveness and potency

Epidemiological studies have associated certain human disease outcomes with particular killer cell Ig-like receptor (KIR) and HLA genotypes. However, the functional explanation for these associations is poorly understood, because the KIRs were initially described as natural killer (NK) cell inhibitory receptors with specificity for HLA molecules on their cellular targets. Yet resolution of infections is often associated with genotypic pairing of inhibitory KIRs with their cognate HLA ligands. Recent studies in mice indicate a second role for MHC-specific inhibitory receptors, i.e., self-MHC recognition confers functional competence on the NK cell to be triggered through their activation receptors, a process termed licensing. As a result, licensed NK cells with self-MHC-specific receptors are more readily activated as compared with unlicensed NK cells without self-MHC-specific receptors. Such results predict that human NK cells may undergo a similar process. Here, we examined the human NK cell subset expressing KIR3DL1, the only known KIR specific for HLA-Bw4 alleles. The KIR3DL1+ subset in normal donors with two HLA-B-Bw4 genes displayed increased responsiveness to tumor stimulation compared with the KIR3DL1+ subset from individuals with only one or no Bw4 genes. By contrast, NK cells lacking KIR3DL1 showed no differences. Therefore, these data indicate that particular KIR and HLA alleles are associated with more responsive NK cells, strongly suggesting that human NK cells are also subjected to NK cell licensing, and providing a potential functional explanation for the influence of KIR and HLA genes in disease as well as interindividual differences in NK cell potency.

The changing prevalence of comorbidity across the age spectrum.

The purpose of the research was to demonstrate that comorbid health conditions disproportionately affect elderly cancer patients. Descriptive analyses and stacked area charts were used to examine the prevalence and severity of comorbid ailments by age of 27,506 newly diagnosed patients treated at one of eight cancer centers between 1998 and 2003. Hypertension was the most common ailment in all patients, diabetes was the second most prevalent ailment in middle-aged patients, and previous solid tumor(s) were the second most prevalent ailment in patients aged 74 and older. Although the prevalence and severity of comorbid ailments including dementia and congestive heart failure increased with age, some comorbidities such as HIV/AIDS and obesity decreased. Advances in cancer interventions have increased survivorship, but the impact of the changing prevalence and severity of comorbidities at different ages has implications for targeted research into targeted clinical and psychosocial interventions.

Clinical outcomes of chronic rhinosinusitis in response to medical therapy: results of a prospective study.

Background Little information exists regarding the outcome of medical management of chronic rhinosinusitis (CRS) in adults. The aim of this study was to examine whether baseline patient demographics, symptoms, objective findings, or treatment strategies were associated with improved CRS outcomes over time. Methods Eighty-four new patients with CRS were evaluated and medically treated for up to 12 months. Patients completed monthly health status questionnaires. The average change of symptom scores using the Sino-Nasal Outcome Test plus one additional symptom–-sense of smell (SNOT-20+1)–-was the primary outcome measure. Results Overall, patients experienced a modest improvement in SNOT-20+1 scores (Δ = -0.61; p< 0.0001), but this did not reach the predetermined level of a clinically meaningful effect (Δ = -0.80). Baseline facial pain or facial pressure was negatively associated with outcome (p = 0.048 and 0.029, respectively) and did not correlate with extent of disease by sinus CT scoring. Other factors, including nasal discharge, hyposmia, cough, nasal polyps, and sinus CT severity, did not predict outcomes. The use of either oral antibiotics or oral steroids was associated with trends toward improved outcomes only when sinus-specific symptoms alone were considered. Conclusion The majority of CRS patients receiving medical treatment show modest improvement over time in SNOT-20+1 scores. Facial pain or facial pressure at entry are negatively associated with outcomes and may reflect causes other than CRS. These findings highlight the limitations of current medical treatment for CRS and the need for novel treatment strategies.

The Effect of Nasally Administered Budesonide Respules on Adrenal Cortex Function in Patients With Chronic Rhinosinusitis

OBJECTIVES To evaluate whether nasal administration of budesonide in adults with chronic rhinosinusitis for 30 days suppresses adrenal function and to assess its clinical efficacy. DESIGN An open-label prospective study. SETTING Academic medical center. PATIENTS We assessed adrenal function in 9 patients using the cosyntropin test before and after budesonide therapy. INTERVENTION Budesonide respule therapy. MAIN OUTCOME MEASURE Scores from the Sino-Nasal Outcome Test-20 (SNOT-20), a tool for assessing rhinosinusitis health and quality of life, were used to assess efficacy of budesonide treatment. RESULTS All of our patients showed adequate adrenal response to cosyntropin stimulation before and after the budesonide trial. The mean difference in SNOT-20 scores was -1 (95% confidence interval, -1.77 to -0.23; P = .02), indicating clinically significant improvement after therapy. CONCLUSION Our findings suggest that using budesonide nasal wash may be clinically effective in decreasing the symptoms of chronic rhinosinusitis and does so without suppression of the hypothalamic-pituitary-adrenal axis in patients with chronic rhinosinusitis.

Impact of Comorbidity on Overall Survival in Patients Surgically Treated for Renal Cell Carcinoma

OBJECTIVES Although the classification of cancer has traditionally focused on the gross and microscopic characteristics of the tumor, the overall health of patients can affect their survival. Because patients with renal cell carcinoma often have other medical conditions, we explored the effect of preexisting medical disease on survival after radical and partial nephrectomy. METHODS From January 1995 to August 2003, the comorbidity status of 697 patients with nonmetastatic renal cell carcinoma who had undergone radical or partial nephrectomy was prospectively coded using the Adult Comorbidity Evaluation-27. Histopathologic review of all slides was performed according to the 2004 World Health Organization scheme. Other variables analyzed included age, sex, ethnicity, pathologic stage, Fuhrman grade, and tumor size. The effect of these factors on overall survival (OS) was analyzed using Cox proportional hazards regression model. RESULTS The median follow-up was 32.2 months for survivors and 36.5 months for all patients. The OS rate at 1, 3, and 5 years was 92.0% (641 patients), 75.3% (525 patients), and 52.7% (367 patients), respectively. Univariate analyses demonstrated that age, comorbidity, tumor size, Fuhrman grade, and pathologic stage were significant predictors of OS. Multivariate analysis revealed that age (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.10 to 1.82, P = .0067), comorbidity (HR 1.37, 95% CI 1.16 to 1.63, P = .0002), pathologic stage (HR 1.97, 95% CI 1.60 to 2.41, P < .0001), and grade (HR 1.83, 95% CI 1.28 to 2.59, P = .0008) predicted for OS. CONCLUSIONS The results of this study have demonstrated that comorbidity is an independent prognostic factor for OS in patients with renal cell carcinoma. Capturing the comorbidity information using validated instruments can improve the preoperative evaluation of patients by providing more accurate prognostic information.

11:06: Effect of Nasal Budesonide Respule on Adrenal Function

tion. In sinuplasty, a balloon catheter is introduced into the sinus under C-Arm fluoroscopy guidance, and the paranasal sinus ostium is dilated, hence relieving blockage. This paper examines the use of image-guided surgery (surgical navigation) to confirm the position of the catheter inside the sinus, and to reduce fluoroscopy time and exposure to radiation. METHODS: Initial study involved cadaver heads to master the technical use of the catheter with the GE surgical navigation system. A prospective clinical study was then designed to include 20 patients with nonpolypoid chronic sinusitis, and compare time to cannulation and success rates using both techniques (surgical navigation vs. C-Arm fluoroscopy). Each patient acted as his/her control, comparing one side to the other. RESULTS: Balloon Sinuplasty catheters achieve an average of 6 to 7 mm dilatation of the sinus ostium in adults and 3 to 5 mm in children. Image-guided surgery is useful both in primary and revision endoscopic sinus surgery and averages a surgical navigation accuracy within 1.5 mm range. New GE image-guided software is now commercially available for use with the Acclarent Sinuplasty catheters. CONCLUSIONS: Image-guided surgery has the potential to reduce fluoroscopy time during Balloon Catheter Sinuplasty.

10:20 AM: RCT of Gabapentin for Relief of Tinnitus

(USVS) have widely varying growth patterns whose causes are poorly understood. The purpose of this study was to determine if there were molecular or clinical correlates of USVS diameter that could be useful in clinical management of the tumors. METHODS: The study population was 65 patients with USVS who were seen at a tertiary surgical referral center. The study assessed maximum tumor diameter, immunochemical growth and proliferation indices, and molecular abnormalities. The immunohistochemical indices were based on monoclonal antibodies to Ki-67 and platelet-derived growth factor (PDGF). The molecular abnormalities were somatic NF2 gene mutations and loss of heterozygosity (LOH). RESULTS: Using multiple linear regression, three covariates were significantly associated with tumor diameter. Tumor diameter decreased with increasing age at diagnosis. Compared to the lowest tercile of PDGF, the highest tercile of PDGF was associated with larger tumor diameter. The presence of LOH was associated with smaller tumor diameter. CONCLUSION: Proliferative activity is an important factor in USVS growth rates. These results should be confirmed in future studies that utilize longitudinal USVS growth rates based on precise volumetrics. SIGNIFICANCE: In future, precise volumetric and proliferative activity of USVS should be studied to determine a more accurate tumor activity. SUPPORT: NF2 Association.