Long- versus short-interval follow-up of cytologically benign thyroid nodules: a prospective cohort study.

BACKGROUND: Thyroid nodules are common, and most are benign. Given the risk of false-negative cytology (i.e. malignancy), follow-up is recommended after 1-2 years, though this recommendation is based solely on expert opinion. Sonographic appearance may assist with planning, but is limited by large inter-observer variability. We therefore compared the safety and efficacy of long- versus short-interval follow-up after a benign initial aspiration, regardless of sonographic appearance. METHODS: This study evaluated all patients referred to the Brigham and Women's Hospital Thyroid Nodule Clinic, between 1999 and 2010, with a cytologically benign nodule >1 cm and who had returned for follow-up sonographic evaluation. Despite standard clinical recommendations, variation in patient compliance resulted in variable follow-up intervals from time of initial aspiration to the first repeat evaluation. Main outcome measures included nodule growth, repeat fine needle aspiration (FNA), thyroidectomy, malignancy, and disease-specific mortality. RESULTS: We evaluated 1,254 patients with 1,819 cytologically benign nodules, with a median time to first follow-up of 1.4 years (range, 0.5-14.1 years). The longer the follow-up interval, the more nodules grew and the more repeat FNAs were performed (P <0.001). The most clinical meaningful endpoints of malignancy or mortality, however, did not differ between the various follow-up intervals. The risk of a thyroidectomy (usually because of compressive symptoms) increased when time to first follow-up exceeded >3 years (4.9% vs. 1.2%, P = 0.0001), though no difference in malignancy risk was identified (0.2-0.8%, P = 0.77). No (0%) thyroid cancer-specific deaths were identified in either cohort. CONCLUSIONS: While expert opinion currently recommends repeat evaluation of a cytologically benign nodule at 1-2 years, these are the first data to demonstrate that this interval can be safely extended to 3 years without increased mortality or patient harm. Nodule growth can be expected, though detection of malignancies is unchanged. While replication of these data in large prospective multicenter studies is needed, this extension in follow-up interval would reduce unnecessary visits and medical interventions for millions of affected patients worldwide, leading to healthcare savings. Please see related commentary article: http://dx.doi.org/10.1186/s12916-016-0559-9 and research article: http://dx.doi.org/10.1186/s12916-015-0419-z .

The variable phenotype and low-risk nature of RAS-positive thyroid nodules.

BACKGROUND: Oncogenic mutations are common in thyroid cancers. While the frequently detected RAS-oncogene mutations have been studied for diagnostic use in cytologically indeterminate thyroid nodules, no investigation has studied such mutations in an unselected population of thyroid nodules. No long-term study of RAS-positive thyroid nodules has been performed. METHODS: We performed a prospective, blinded cohort study in 362 consecutive patients presenting with clinically relevant (>1 cm) thyroid nodules. Fine needle aspiration cytology and mutational testing were obtained for all nodules. Post-operative histopathology was obtained for malignant or indeterminate nodules, and benign nodules were sonographically followed. Histopathological features were compared between RAS- and BRAF-positive malignancies. RAS-positive benign nodules were analyzed for growth or cellular change from prior aspirations. RESULTS: Overall, 17 of 362 nodules were RAS-positive. Nine separate nodules were BRAF-positive, of which eight underwent surgery and all proved malignant (100%). Out of the 17 RAS-positive nodules, ten underwent surgery, of which eight proved malignant (47%). All RAS-positive malignancies were low risk - all follicular variants of papillary carcinoma, without extrathyroidal extension, metastases, or lymphovascular invasion. RAS-positivity was associated with malignancy in younger patients (P = 0.028). Of the nine RAS-positive benign nodules, five had long-term prospective sonographic follow-up (mean 8.3 years) showing no growth or signs of malignancy. Four of these nodules also had previous aspirations (mean 5.8 years prior), all with similar benign results. CONCLUSIONS: While RAS-oncogene mutations increase malignancy risk, these data demonstrate a low-risk phenotype for most RAS-positive cancers. Furthermore, cytologically benign, yet RAS-positive nodules behave in an indolent fashion over years. RAS-positivity alone should therefore not dictate clinical decisions.

Clinical experience following implementation of routine SPECT-CT imaging following 131-iodine administration for thyroid cancer.

Background: Planar scintigraphy has long been indicated in patients receiving I-131 therapy for thyroid cancer to determine the anatomic location of metastases. We studied our experience upon implementing additional single-photon emission (SPECT)-CT scanning in these patients. Method: We performed a retrospective study of consecutive adult patients with newly diagnosed thyroid cancer treated with I-131 between 2011 and 2017. Radiologic findings detected with planar scintigraphy alone vs those identified with SPECT-CT scanning were primary endpoints. Result: In this study, 212 consecutive patients with thyroid cancer were analyzed in two separate cohorts (107 planar scintigraphy alone and 105 planar scintigraphy with SPECT-CT). The addition of SPECT-CT resulted in more findings, both thyroid-related and incidental. However, we identified only 3 of 21 cases in which SPECT-CT provided an unequivocal additional benefit by changing clinical management beyond planar scintigraphy alone. No difference in the detection of distant metastatic disease or outcome was identified between cohorts. Conclusion: Synergistic SPECT-CT imaging in addition to planar nuclear scintigraphy adds limited clinical value to thyroid cancer patients harboring a low risk of distant metastases, while frequently identifying clinically insignificant findings. These data from a typical cohort of patients receiving standard thyroid cancer care provide insight into the routine use of SPECT-CT in such patients.

Independent Comparison of the Afirma Genomic Sequencing Classifier and Gene Expression Classifier for Cytologically Indeterminate Thyroid Nodules.

Background: For thyroid nodules with indeterminate cytology, the Afirma Gene Expression Classifier (GEC) identified benign nodules to reduce diagnostic surgery, though many nodules classified as suspicious still proved histopathologically benign. The current Afirma Genomic Sequencing Classifier (GSC) demonstrates improved specificity, suggesting more nodules will have a benign result (benign call rate [BCR]), but independent data are needed to confirm this in clinical practice. Methods: Retrospective analysis was performed of all Bethesda III or IV cytology thyroid nodules ≥1 cm tested with GEC (between January 1, 2011, and July 19, 2017) or GSC (between July 20, 2017, and August 27, 2018) at the authors' institution. Afirma testing was not performed reflectively for all nodules with Bethesda III or IV cytology, but rather was applied based on physician-patient decision making. Demographic, sonographic, and cytologic data were collected. The BCR for GEC- versus GSC-tested nodules was compared and further stratified by Bethesda classifications. Results: The study evaluated 600 nodules in 563 patients tested with either GEC (n = 486) or GSC (n = 114). The BCR was 233/486 (47.9%) for the GEC compared to 75/114 (65.8%) for the GSC (p = 0.0006). Hürthle-cell cytology was present in 99/486 (20.4%) nodules in the GEC group compared to 31/114 (27.2%) nodules in the GSC group (p = 0.28). The GSC BCR was significantly higher than the GEC BCR for Bethesda III nodules characterized by Hürthle cells (p = 0.006), but the BCRs were similar for nodules with architectural or cytologic atypia. In Bethesda IV nodules suspicious for follicular neoplasm, BCR for the GEC and GSC were similar (p = 0.68), but for cytology suspicious for Hürthle-cell neoplasm, the GSC BCR was 68.2% (15/22) compared to the GEC BCR of 16.4% (10/61; p < 0.0001). Positive predictive value in resected nodules with a suspicious result was 16/32 (50%) for GSC nodules and 75/221 (33.9%) for GEC nodules (p = 0.1). Conclusions: The higher BCR for the GSC compared to the GEC for indeterminate thyroid nodules, predominantly among nodules with Hürthle-cell cytology, will likely lead to further reduction in surgical management.

A Cohort Analysis of Clinical and Ultrasound Variables Predicting Cancer Risk in 20,001 Consecutive Thyroid Nodules.

CONTEXT: Assessing thyroid nodules for malignancy is complex. The impact of patient and nodule factors on cancer evaluation is uncertain. OBJECTIVES: To determine precise estimates of cancer risk associated with clinical and sonographic variables obtained during thyroid nodule assessment. DESIGN: Analysis of consecutive adult patients evaluated with ultrasound-guided fine-needle aspiration for a thyroid nodule ≥1 cm between 1995 and 2017. Demographics, nodule sonographic appearance, and pathologic findings were collected. MAIN OUTCOME MEASURES: Estimated risk for thyroid nodule malignancy for patient and sonographic variables using mixed-effect logistic regression. RESULTS: In 9967 patients [84% women, median age 53 years (range 18 to 95)], thyroid cancer was confirmed in 1974 of 20,001 thyroid nodules (9.9%). Significant ORs for malignancy were demonstrated for patient age <52 years [OR: 1.82, 95% CI (1.63 to 2.05), P < 0.0001], male sex [OR: 1.68 (1.45 to 1.93), P < 0.0001], nodule size [OR: 1.30 (1.14 to 1.49) for 20 to 19 mm, OR: 1.59 (1.34 to 1.88) for 30 to 39 mm, and OR: 1.71 (1.43 to 2.04) for ≥40 mm compared with 10 to 19 mm, P < 0.0001 for all], cystic content [OR: 0.43 (0.37 to 0.50) for 25% to 75% cystic and OR: 0.21 (0.15 to 0.28) for >75% compared with predominantly solid, P < 0.0001 for both], and the presence of additional nodules ≥1 cm [OR: 0.69 (0.60 to 0.79) for two nodules, OR: 0.41 (0.34 to 0.49) for three nodules, and OR: 0.19 (0.16 to 0.22) for greater than or equal to four nodules compared with one nodule, P < 0.0001 for all]. A free online calculator was constructed to provide malignancy-risk estimates based on these variables. CONCLUSIONS: Patient and nodule characteristics enable more precise thyroid nodule risk assessment. These variables are obtained during routine initial thyroid nodule evaluation and provide new insights into individualized thyroid nodule care.

Quantitative Analysis of the Benefits and Risk of Thyroid Nodule Evaluation in Patients ≥70 Years Old.

BACKGROUND: In older patients, thyroid nodules are frequently detected and referred for evaluation, though usually prove to be benign disease or low-risk cancer. Therefore, management should be guided not solely by malignancy risk, but also by the relative risks of any intervention. Unfortunately, few such data are available for patients ≥70 years old. METHODS: All consecutive patients ≥70 years old assessed by ultrasound (US) and fine-needle aspiration (FNA) between 1995 and 2015 were analyzed. Clinical, US, and histologic data, including patient comorbidities and outcomes, were obtained. Imaging and cytology results from initial evaluation were reviewed to detect significant-risk thyroid cancer (SRTC), which was defined as anaplastic, medullary, or poorly differentiated carcinoma, or the presence of distant metastases. Overall survival analyses were then performed to assist with risk-to-benefit assessment. RESULTS: A total of 1129 patients ≥70 years old with 2527 nodules ≥1 cm were evaluated. FNA was safe in all, and cytology proved benign in 67.3% of patients. However, FNA led to surgery in 208 patients, of whom 93 (44.7%) had benign histopathology. Among all patients who underwent FNA, only 17 (1.5%) SRTC were identified, all of which were preoperatively identifiable by imaging and/or cytology. These SRTC were responsible for all (n = 10; 0.9%) thyroid cancer deaths. Among all other patients (n = 1112), 160 deaths (14.4%) were confirmed during a median follow-up of four years. None of these were thyroid cancer related. Survival analysis for these 1112 patients demonstrated that a separate non-thyroidal malignancy or coronary artery disease at the time of nodule evaluation was associated with increased mortality compared to those without these diagnoses (hazard ratio = 2.32 [confidence interval 1.66-3.26]; p < 0.01), confirming these are important variables to identify prior to thyroid nodule evaluation. CONCLUSIONS: For patients ≥70 years old, US and FNA are safe and prove helpful in identifying SRTC and benign cytology. However, the surgical management of patients ≥70 years old presenting without high-risk findings should be tempered, especially when comorbid illness is identified.

Qualifiers of atypia in the cytologic diagnosis of thyroid nodules are associated with different Afirma gene expression classifier results and clinical outcomes.

BACKGROUND: Thyroid nodules with atypia of undetermined significance (AUS) on fine-needle aspiration (FNA) have a low risk of malignancy that appears to vary based on specific features described in the AUS diagnosis. The Afirma gene expression classifier (GEC) is a molecular test designed to improve preoperative risk stratification of thyroid nodules, but its performance for different patterns of AUS has not been defined. The objective of this study was to assess GEC results and clinical outcomes in AUS nodules with architectural atypia (AUS-A), cytologic atypia (AUS-C) or both (AUS-C/A). METHODS: This was a retrospective review of all thyroid nodules with AUS cytopathology that underwent GEC testing at the authors' institution over a period of >4 years. RESULTS: In 227 nodules that had AUS cytology results and Afirma GEC testing, the rate of benign GEC results was higher in AUS-A nodules (70 of 107; 65%) than in AUS-C/A nodules (25 of 65; 38%; P = .0008), and AUS-C nodules exhibited an intermediate rate of benign results (27 of 55 nodules; 59%). The risk of cancer among patients who had GEC-suspicious nodules, 86% of whom underwent resection, was 19% (6 of 25) for AUS-A nodules compared with 57% (21 of 37) for AUS-C/A nodules (P = .003) and 45% (10 of 22) for AUS-C nodules (P = .07). In nodules that had an indeterminate repeat cytology result, no difference was observed in the rate of benign GEC results or in the malignancy rate compared with nodules that had a single cytology result. CONCLUSIONS: The performance characteristics of Afirma GEC testing vary, depending on qualifiers of cytologic atypia. Recognition of these differences may enable clinicians to provide improved counseling and treatment recommendations to patients. Cancer Cytopathol 2017;125:313-322. © 2017 American Cancer Society.

Differential Growth Rates of Benign vs. Malignant Thyroid Nodules.

Context: Thyroid nodule growth was once considered concerning for malignancy, but data showing that benign nodules grow questioned the use of this paradigm. To date, however, no studies have adequately evaluated whether growth rates differ in malignant vs. benign nodules. Objective: To sonographically evaluate growth rates in benign and malignant thyroid nodules ≥1 cm. Design: Prospective, cohort study of patients with tissue diagnosis of benign or malignant disease, with repeated ultrasound evaluation six or more months apart. Main Outcomes: Growth rate in largest dimension of malignant compared with benign thyroid nodules. Regression models were used to evaluate predictors of growth. Results: Malignant nodules (126) met inclusion criteria (≥6-month nonoperative followup) and were compared with 1363 benign nodules. Malignant nodules were not found to be uniquely selected or prospectively observed solely for low-risk phenotype. Median ultrasound intervals were similar (21.8 months for benign nodules; 20.9 months for malignant nodules). Malignant nodules were more likely to grow >2 mm/y compared with benign nodules [relative risk (RR) = 2.5, 95% confidence interval (CI), 1.6 to 3.1; P < 0.001], which remained true after adjustment for clinical factors. The RR of a nodule being malignant increased with faster growth rates. Malignant nodules growing >2 mm/y had greater odds of being more aggressive cancers [intermediate risk: odds ratio (OR) = 2.99; 95% CI, 1.20 to 7.47; P = 0.03; higher risk: OR = 8.69; 95% CI, 1.78 to 42.34; P = 0.02]. Conclusions: Malignant nodules, especially higher-risk phenotypes, grow faster than benign nodules. As growth >2 mm/y predicts malignant compared with benign disease, this clinical parameter can contribute to the assessment of thyroid cancer risk.

An integrated graphic scheme for the display of insulin prescription and blood glucose information.

OBJECTIVE: This study was undertaken to determine whether use of an integrated graphic scheme for the display of insulin prescription and blood glucose information has an impact on simulated decision-making in clinical practice. METHODS: Five test cases representing patients treated with multiple daily insulin regimens were selected from a database of stored blood glucose readings. Five endocrinologists made treatment recommendations based on review of aggregated readings and corresponding insulin prescriptions. Twenty subjects were randomized to complete two sets of sequential real-time data management exercises. One set focused on evaluation of insulin prescriptions and readings printed as entries in logbooks. The other focused on evaluation of displays of insulin doses and readings plotted out according to an integrated graphic scheme of representation. RESULTS: Subjects were more likely to make correct decisions in four out of five test cases after reviewing displays. Subjects were less likely to make incorrect decisions in all of five test cases after reviewing displays. Completion times were 30-66% shorter for exercises involving review of displays. CONCLUSION: An integrated graphic scheme that associates representations of insulin doses with metaphor graphic displays of aggregated blood glucose readings may facilitate decisionmaking in clinical practice.

Bethesda Categorization of Thyroid Nodule Cytology and Prediction of Thyroid Cancer Type and Prognosis.

BACKGROUND: Since its inception, the Bethesda System for Reporting Thyroid Cytopathology (TBS) has been widely adopted. Each category conveys a risk of malignancy and recommended next steps, though it is unclear if each category also predicts the type and extent of malignancy. If so, this would greatly expand the utility of the TBS by providing prognostic information in addition to baseline cancer risk. METHODS: All patients prospectively enrolled into the authors' thyroid nodule database from 1995 to 2013 with histologically proven malignancy were analyzed. The primary ultrasound-guided fine-needle aspiration cytology (AUS, atypia of unknown significance; FN, follicular neoplasm; SUSP, suspicious; M, malignant) was correlated with the type of thyroid cancer and histological features known to impact prognosis and recurrence, including lymph node metastasis (LNM), lymphovascular invasion, and extrathyroidal extension (ETE). Primary cytology was separately correlated with higher risk malignancy. RESULTS: A total of 1291 malignancies were identified, with primary cytology AUS in 130 cases, FN in 241 cases, SUSP in 411 cases, and M in 509 cases. AUS, SUSP, and M cytology were progressively associated with an increasing risk of high-risk disease (p < 0.001), LNM (p < 0.001), ETE (p < 0.001), and margin positivity (p < 0.001). Notably, 71% of malignancies with AUS cytology were follicular variants of papillary thyroid cancer compared with 63% with SUSP cytology and only 20% with M cytology. In contrast, high-risk malignancies were diagnosed in only 4% with AUS cytology, but 9% and 27% with SUSP and M cytology, respectively. FN conveyed a significantly increased risk of follicular thyroid carcinoma compared with all other types (28% vs. 2%; p < 0.001). A composite endpoint of recurrence, distant metastases, and death similarly increased as cytology progressed from AUS to SUSP to M (p < 0.001). CONCLUSION: In addition to predicting cancer prevalence, the TBS also imparts important prognostic information about cancer type, variant, and risk of recurrence. These data extend the utility of TBS classification by fostering an improved understanding of the risk posed by any confirmed malignancy.

Afirma Benign Thyroid Nodules Show Similar Growth to Cytologically Benign Nodules During Follow-Up.

CONTEXT: The Afirma gene expression classifier (GEC) is a molecular diagnostic test that has a high negative predictive value for ruling out malignancy in thyroid nodules with indeterminate cytology. Many patients with a cytologically indeterminate and GEC benign (Cyto-I/GEC-B) nodule undergo monitoring instead of diagnostic surgery, but few data describe their follow-up. OBJECTIVE: The objective of the study was to determine the sonographic changes and clinical outcomes for patients with Cyto-I/GEC-B nodules compared with patients with cytologically benign (Cyto-B) nodules. DESIGN: This was a retrospective analysis of consecutive Cyto-I/GEC-B nodules evaluated at Brigham and Women's Hospital compared with Cyto-B nodules. MAIN OUTCOMES: Nodule growth of 20% or greater in two dimensions or of 50% or greater in volume, change in sonographic features, and rates of repeat fine-needle aspiration, thyroidectomy, and malignancy. RESULTS: Ninety-five Cyto-I/GEC-B nodules in 90 patients were identified. Five patients underwent primary surgical resection. Of the remaining 90 nodules, 58 (64.4%) had sonographic follow-up available at a median of 13 months (range 4-40 mo). Cyto-I/GEC-B nodules showed similar growth compared with 1224 Cyto-B nodules using either of the following criteria: 20% or greater in two dimensions (8.6% vs 8.3%, P = .80) or 50% or greater in volume (17.2% vs 13.8%, P = .44). Thyroidectomies were more frequent in the Cyto-I/GEC-B group (13.8% vs 0.9%, P < .0001), but cancer was found in only one patient, with no evidence of persistent disease after initial treatment. CONCLUSIONS: Cyto-I/GEC-B nodules demonstrate similar growth to Cyto-B nodules during follow-up. Although Cyto-I/GEC-B nodules were more frequently resected, only one malignancy was found. These data suggest that reassessment of Cyto-I/GEC-B nodules may be performed similarly to those with benign cytology.

The Influence of Patient Age on Thyroid Nodule Formation, Multinodularity, and Thyroid Cancer Risk.

INTRODUCTION: Although advancing age is known to influence the formation of thyroid nodules, the precise relationship remains unclear. Furthermore, it is uncertain whether age influences the risk that any thyroid nodule may prove cancerous. AIM: The aim was to determine the impact of patient age on nodule formation, multinodularity, and risk of thyroid malignancy. METHOD: We conducted a prospective cohort analysis of consecutive adults (ages 20-95 y) who presented for evaluation of nodular disease from 1995 to 2011. A total of 6391 patients underwent ultrasound and fine-needle aspiration of 12 115 nodules ≥ 1 cm. Patients were divided into six age groups and compared using sonographic, cytological, and histological endpoints. RESULT: The prevalence of thyroid nodular disease increases with advancing age. The mean number of nodules at presentation increased from 1.5 in the youngest cohort (age, 20-30 y) to 2.2 in the oldest cohort (age, >70 y; P < .001), demonstrating a 1.6% annual increased risk for multinodularity (odds ratio, 1.02; P < .001). In contrast, the risk of malignancy in a newly identified nodule declined with advancing age. Thyroid cancer incidence per patient was 22.9% in the youngest cohort, but 12.6% in the oldest cohort (odds ratio, 0.972; P < .001), demonstrating a 2.2% decrease per year in the relative risk of malignancy between ages 20 and 60 years, which stabilized thereafter. Despite a lower likelihood of malignancy, identified cancers in older patients demonstrated higher risk histological phenotypes. Although nearly all malignancies in younger patients were well-differentiated, older patients were more likely to have higher risk papillary thyroid carcinoma variants, poorly differentiated cancer, or anaplastic carcinoma (P < .001). CONCLUSION: With advancing age, the prevalence of clinically relevant thyroid nodules increases, whereas the risk that such nodules are malignant decreases. Nonetheless, when thyroid cancer is detected in older individuals, a higher-risk histological phenotype is more likely. These data provide insight into the clinical paradox that confronts physicians managing this common illness.

Personal health records: evaluation of functionality and utility.

OBJECTIVES: Web-based applications have been developed that allow patients to enter their own information into secure personal health records. These applications are being promoted as a means of providing patients and providers with universal access to updated medical information. The authors evaluated the functionality and utility of a selection of personal health records. DESIGN: A targeted search strategy was used to identify eleven Web sites promoting different personal health records. Specific criteria related to the entry and display of data elements were developed to evaluate the functionality of each PHR. Information abstracted from an actual case was used to create a series of representative PHRs. Output generated for review was evaluated to assess the accuracy and completeness of clinical information related to the diagnosis and treatment of specific disorders. RESULTS: The PHRs selected for review employed data entry methods that limited the range and content of patient-entered information related to medical history, medications, laboratory tests, diagnostic studies, and immunizations. Representative PHRs created with information abstracted from an actual case displayed varying amounts of information at basic and comprehensive levels of representation. CONCLUSIONS: Currently available PHRs demonstrate limited functionality. The data entry, validation, and information display methods they employ may limit their utility as representations of medical information.

Patient entry of information: evaluation of user interfaces.

BACKGROUND: Personal health records are web-based applications that allow patients to directly enter their own data into secure repositories in order to generate accessible profiles of medical information. OBJECTIVE: The authors evaluated a variety of user interfaces to determine whether different types of data entry methods employed by Personal health records may have an impact on the accuracy of patient-entered medical information. METHODS: Patients with disorders requiring treatment with thyroid hormone preparations were recruited to enter data into a web-based study application. The study application presented sequences of exercises that prompted free text entry, pick list selection, or radio button selection of information related to diagnoses, prescriptions, and laboratory test results. Entered data elements were compared to information abstracted from patients' clinic notes, prescription records, and laboratory test reports. RESULTS: Accuracy rates associated with the different data entry methods tested varied in relation to the complexity of requested information. Most of the data entry methods tested allowed for accurate entry of thyroid hormone preparation names, laboratory test names, and familiar diagnoses. Data entry methods that prompted guided abstraction of data elements from primary source documents were associated with more accurate entry of qualitative and quantitative information. CONCLUSIONS: Different types of data entry methods employed by Personal health records may have an impact on the accuracy of patient-entered medical information. Approaches that rely on guided entry of data elements abstracted from primary source documents may promote more accurate entry of information.

Long-term, treatment-free survival in select patients with distant metastatic papillary thyroid cancer.

Well-differentiated thyroid carcinoma (WDTC) generally has a favorable prognosis. However, patients with distant metastatic disease experience progression of disease with a higher mortality. A subset of patients not previously described may challenge the conventional dogma regarding the progressive nature of all metastatic WDTC. Through analysis of our database, we identified patients with distant metastatic WDTC and persistent, minimally progressive disease. In all patients, persistent metastatic disease was confirmed via tissue biopsy, abnormal PET scan, and/or biochemical elevations in thyroglobulin or antibody levels. Progression of disease was monitored clinically and with repeat imaging. We describe five patients with WDTC and pulmonary metastases, aged 8-43 years at diagnosis. All patients underwent initial surgery and radioactive iodine (RAI) ablation, with some receiving multiple treatments. Persistent pulmonary metastatic disease was confirmed over decades (mean 22 years, range 8-42 years) with minimal progression despite no further treatment beyond thyroid hormone suppression. Persistent disease was biopsy-proven in all patients at a mean of 9.6 years from last RAI treatment. All patients had elevated thyroglobulin or anti-thyroglobulin antibody levels, while three demonstrated metabolically active disease with positive FDG uptake on PET scan, and one patient with persistent radioactive iodine avid pulmonary metastasis 36 years after her last RAI treatment. This case series demonstrates that some patients with distant metastases, even if metabolically active and radioactive iodine resistant, remain stable for decades without further treatment. Clinical awareness of such patients and continual reassessment of disease risk following initial therapy are crucial as aggressive treatment may not be necessary.

Diagnostic use of molecular markers in the evaluation of thyroid nodules.

OBJECTIVE: To describe the molecular markers thus far evaluated for use in the care of patients with clinically relevant thyroid nodules. METHODS: We review the currently available molecular tests that have been applied to patients with thyroid nodules. RESULTS: In the United States, approximately 450 000 diagnostic fine-needle aspirates will be performed on patients with thyroid nodules this year in an effort to identify thyroid cancer. Unfortunately, this test is imprecise and, at times, inaccurate. Because of this, novel diagnostic testing modalities have been pursued, the most promising of which involve molecular analysis of thyroid tissue. Immunohistochemical staining, analysis for mutations and gene rearrangements, and microarray analysis have all been investigated with regard to their performance characteristics in targeted patient populations. CONCLUSIONS: Molecular tests to evaluate thyroid nodules demonstrate variable performance characteristics. Further evaluation of available and emerging molecular tests will necessarily rely on prospective real-world test validation in the clinical setting.

Iterative user-centered design of a next generation patient monitoring system for emergency medical response.

We have developed a system for real-time patient monitoring during large-scale disasters. Our system is designed with scalable algorithms to monitor large numbers of patients, an intuitive interface to support the overwhelmed responders, and ad-hoc mesh networking capabilities to maintain connectivity to patients in the chaotic settings. This paper describes an iterative approach to user-centered design adopted to guide development of our system. This system is a part of the Advanced Health and Disaster Aid Network (AID-N) architecture.