Catherine B. Barden

Discrimination of Benign and Malignant Thyroid Nodules by Molecular Profiling

Background:The evaluation of thyroid nodules by fine-needle aspiration has been the standard for almost 30 years, despite significant shortcomings in sensitivity and specificity. Recent data from our laboratory have suggested that molecular profiling permits the discrimination of specific types of thyroid nodules. These studies were undertaken to determine whether molecular profiling can discriminate between benign and malignant thyroid nodules with the necessary sensitivity and specificity required of a screening test. Methods:Molecular profiles of 11 papillary thyroid carcinomas, 13 follicular variant of papillary thyroid carcinomas, 9 follicular thyroid carcinomas, and 26 benign tumors (follicular adenomas and hyperplastic nodules) were analyzed by oligonucleotide microarray analysis. A gene list was created based on 45 samples. Seventeen samples were then added to the analysis as unknowns. A hierarchical clustering analysis was performed on all 62 samples to examine the groups for potential differences and the ability of the gene list to distinguish tumor types. Results:Cluster analysis of all 62 samples produced 2 distinct groups, 1 containing the carcinomas and 1 containing the benign lesions. The sensitivity for a diagnosis of cancer was 91.7% with a specificity of 96.2% (3 follicular variant of papillary thyroid carcinomas clustered with the benign lesions). The cancer gene profiles contained both known cancer-associated genes (MET, galectin-3) and previously unidentified genes. Conclusions:Molecular profiling readily distinguishes between benign and malignant thyroid tumors with excellent sensitivity and specificity. Elucidated genes may provide insight into the molecular pathogenesis of thyroid cancer. Gene profiling may significantly enhance the evaluation of thyroid nodules in the future.

Renal Cell Carcinoma Induces Prostaglandin E2 and T-Helper Type 2 Cytokine Production in Peripheral Blood Mononuclear Cells

AbstractBackground: Patients with renal cell carcinoma (RCC) do not develop an effective antitumor immune response, despite significant infiltration by lymphocytes. Tumor production of immunosuppressive factors may account for this failure. The object of this study was to investigate the production of immunosuppressive mediators, especially prostaglandin E2 (PGE2), by RCC. Methods: Peripheral blood mononuclear cells (PBMC) were cocultured with conditioned medium (CM) from human RCC cell lines in the presence or absence of NS-398, a selective cyclooxygenase 2 (COX-2) inhibitor. Supernatants were analyzed for levels of PGE2, interleukin (IL)-10, IL-6, IL-2, interferon-γ, and IL-12. The effects of RCC CM on PBMC proliferation were also examined. The expression of basal and stimulated COX-2 messenger RNA in the cell lines was assessed by reverse transcriptase-polymerase chain reaction. Results: RCC CM significantly increased PGE2 production by PBMC. T-helper type 2 (Th2) cytokine production was also significantly increased. Th1 cytokines were unchanged or decreased. RCC CM increased proliferation of PBMC. Coculture with NS-398 reduced PBMC PGE2 production to below control levels and significantly decreased IL-6 production and PBMC proliferation. NS-398 had no effect on cellular production of IL-10 or Th1 cytokines. Conclusions:Human RCC inhibits the host antitumor immune response by promoting PGE2 production and Th2 cytokines in PBMC. Selective inhibition of COX-2 may have a role in abrogating this effect.

Characteristics of patients having thyroid surgery under Regional anesthesia

BACKGROUND Recently local/regional anesthesia has been reintroduced as an alternative to general anesthesia for thyroidectomy. This study was undertaken to analyze characteristics and outcomes of patients who had thyroid surgery performed under regional anesthesia compared with those who had thyroidectomy under general anesthesia. STUDY DESIGN One hundred seventy-five consecutive patients who underwent thyroid surgery under regional or general anesthesia during a 3-year period were analyzed. Fifty-eight operations were performed under regional anesthesia and 116 under general anesthesia. Patient characteristics analyzed included age, gender, obesity, anesthesia class, and tumor pathology. Postoperative complications, including nausea or vomiting, were compared. Additionally, operative times and length of stay in each group were compared. RESULTS Patient characteristics including age, gender, tumor pathology, and anesthesia class were similar in both groups. But only 2% of patients treated under regional anesthesia were obese compared with 23% under general anesthesia. Although not significant, there was a trend toward decreased incidence of nausea and vomiting in the regional group. Other complications for the regional and general anesthesia groups were equal at 3%. Two patients required conversion to general anesthesia. Complications in the general anesthesia group included one episode of transient symptomatic hypocalcemia, two patients with transient vocal cord paralysis, and one episode of hematoma. Finally, there was a statistically significant increase in total operating room time and length of stay for the general anesthesia group. CONCLUSIONS Regional anesthesia is a safe alternative to general anesthesia for patients undergoing thyroid surgery. Patients who cannot communicate verbally with the surgical team or who are obese may not be ideal candidates for regional anesthesia. The use of regional anesthesia results in a decreased length of stay and similar operative and operating room times.

Socioeconomic Factors, not Ethnicity, Predict Breast Self-Examination

Abstract: The American Cancer Society has recommended monthly breast self‐examinations (BSEs) to aid in the early detection of breast cancer. Compliance with BSE recommendations has been shown to be decreased in certain ethnic groups. This investigation evaluates relevant variables involved in BSE compliance in an urban breast cancer screening center. A survey over a 1‐year period (June 1996–June 1997) was given to all patients on their initial visit to the Breast Health Center at Tulane University Medical Center. Demographic and socioeconomic factors associated with the compliance of BSE were explored. The overall rate of BSE was relatively high at 80%. There was no difference between ethnic groups in rates of BSE (Caucasians 21% versus African Americans 20%). Statistically significant variables associated with BSE noncompliance were high school education (did not complete high school 16% versus completed high school 33%; p < 0.0004), employment status (employed 16% versus unemployed 31%; p < 0.0004), and marital status (married 15% versus single/divorced 22%; p < 0.05). While the majority of women in our study practiced BSE and ethnicity did not predict BSE, several socioeconomic factors were predictive of BSE compliance. Efforts to increase community outreach to lower socioeconomic patients as well as efforts to ensure proficient BSE techniques by patients may help detect early breast cancer.

Anesthesiology residents' medical school debt influence on moonlighting activities, work environment choice, and debt repayment programs: A nationwide survey

BACKGROUND: The amount of education debt incurred by medical school graduates in the United States has grown considerably over the last 30 years; it has outpaced inflation to reach a mean of

COX-2 up-regulation in idiopathic carpal tunnel syndrome

158,000. With this dramatic increase in education debt, there has been limited information on how medical school debt loads of anesthesiology physicians impact their decisions concerning moonlighting and future career choices. Our aim was to survey current anesthesiology interns, residents, and fellows to assess the correlation between the amount of medical school debt they had collected and (1) their outlook toward moonlighting activities, (2) future career plans, and (3) choice of employer with a debt repayment program. METHODS: We developed a web-based survey instrument and contacted residency training programs to obtain access to their anesthesiology interns, residents, and fellows (residents). We assessed each relationship of interest using a multivariable proportional odds model, adjusting for all available baseline potential confounding factors. Second, we compared participants with >

Serum leptin levels in acute protein deprivation.

150,000 medical school debt versus participants with no debt on the same questions of interest, each using a multivariable proportional odds model with the same covariable adjustment. RESULTS: We had access to 2386 residents through their training programs and 537 completed the survey. Those respondents with a 1-category-larger amount of medical school debt (i.e.,

Classification of follicular thyroid tumors by molecular signature: Results of gene profiling

30,000) were associated with 7%(99.3% confidence interval: 0%, 13%) increased odds of having the desire to moonlight during residency/fellowship, and were associated with 7% (1%, 13%) decreased odds of saying they would choose a career as an academic faculty, respectively. Also, those with a larger amount of medical school debt were more likely to be swayed to be interested in an anesthesiology group with an education debt repayment program (odds ratio: 1.3 [1.22, 1.39] for 1-category increase in the debt amount); furthermore, the corresponding odds ratio was increased to 4.6 (2.8, 7.5) comparing those with >

Antisense hTERT inhibits thyroid cancer cell growth.

150,000 debt with those without debt. CONCLUSIONS: In an effort to compete with private practice anesthesiology groups and to reduce the impact of debt on future career choices of residents/fellows, academic anesthesiology groups would do well to (1) promote moonlighting activities that are within the Accreditation Council for Graduate Medical Education and institutional guidelines, (2) develop financial curriculum for residents/fellows, and (3) offer debt repayment programs as an incentive for new faculty to join academic medicine.

p44/p42-MAP kinase expression in papillary thyroid carcinomas

The objective of this study was to determine whether cyclooxygenase-2 (COX-2) is up-regulated in the synovium of patients with carpal tunnel syndrome. Twenty patients were enrolled: 16 consecutive patients with carpal tunnel syndrome and four control patients (exploration for non–carpal tunnel syndrome–related wrist or forearm pathology). Clinical data (demographics, pertinent history, symptomatology) were obtained preoperatively. Flexor tenosynovial tissue was isolated from all patients and clinically graded as thin, intermediate, or thick. Histologic evaluation was conducted to rule out the presence of inflammatory cells. Immunohistochemical staining for COX-2 was performed. The immunohistochemical data were confirmed by reverse transcriptase-polymerase chain reaction analysis of COX-2 mRNA. Results showed that the majority of carpal tunnel syndrome specimens (88 percent) showed synovial hypertrophy compared with 0 percent of the controls (p < 0.05). Also, 69 percent of carpal tunnel syndrome specimens (11 of 16) versus 0 percent of controls (zero of four) stained positively for COX-2 (p < 0.05). Of the carpal tunnel syndrome patients, 91 percent of thick specimens versus 33 percent of intermediate specimens versus 0 percent of thin specimens showed COX-2 staining. The authors conclude that synovial hypertrophy is a prominent finding in carpal tunnel syndrome. COX-2 is up-regulated in the tenosynovium of patients with carpal tunnel syndrome, and this upregulation may correlate with the clinical grade of the tenosynovium. The role of COX-2 in carpal tunnel syndrome may be to mediate remodeling of pathologic tissue. To this end, it may be a potential therapeutic target for specific inhibition.