Active Surveillance for Low-Risk Differentiated Thyroid Cancer.

Less aggressive treatment options, including hemithyroidectomy and active surveillance, have been accepted as treatment options for low-risk small, differentiated thyroid carcinoma (DTC). Multiple studies have shown a low rate of cancer growth and lymph node metastases and no evidence of distant metastases during active surveillance of low-risk small DTC. However, not all patients with low -risk small DTC are ideal or appropriate candidate for active surveillance. Patients with thyroid cancer adjacent to either the trachea or recurrent laryngeal nerve or those with evidence of extrathyroidal extension, a high-risk molecular profile, lymph node, or distant metastases are considered inappropriate candidates for active surveillance. In addition, there are other essential factors that clinicians should consider while recommending active surveillance, including patient financial and insurance status; availability of high-quality neck ultrasounds and experienced radiologists, endocrinologists, and surgeons; and patient preference, level of anxiety, and willingness to undergo prolonged surveillance and follow-up imaging.

Performance of Thyroid-Stimulating Immunoglobulin Bioassay and Thyrotropin-Binding Inhibitory Immunoglobulin Assay for the Diagnosis of Graves' Disease in Patients With Active Thyrotoxicosis.

OBJECTIVE: Graves' disease (GD) is caused by the stimulation of thyrotropin receptors by autoantibodies. We compared the diagnostic accuracy of the thyroid-stimulating immunoglobulin (TSI) bioassay and thyrotropin-binding inhibitory immunoglobulin (TBII) assay in differentiating GD from other causes of thyrotoxicosis. METHODS: We retrospectively evaluated 493 patients with thyrotoxicosis who were tested with the third-generation TSI and TBII assays simultaneously. Patients were classified according to the clinical, histopathologic, and imaging criteria into the following groups: positive reference group (PRG) (patients with GD), negative reference group (NRG) (patients without GD), and inconclusive group (patients without a definitive diagnosis). RESULTS: TSI and TBII assays were concordant in 88% of the cases and showed a strong positive correlation (rs = 0.844, P < .01). When analyzed collectively, TSI and TBII assays confirmed the diagnosis of GD in 79% of the PRG cases and excluded GD in 92.5% of patients in NRG. Combined TSI and TBII assays or TBII assay alone showed similar accuracy to the diagnosis of GD (81.4% and 77.5%, respectively). Tests in 40 of 191 patients in PRG were negative for both TSI and TBII assays, whereas 3 of 40 cases in NRG had at least 1 positive thyrotropin receptor antibody test. False-negative cases were associated with subclinical hyperthyroidism, normal radionuclide uptake, longer duration of thyrotoxicosis, and absence of goiter or Graves' ophthalmopathy. CONCLUSION: TSI and TBII assays showed similar performance in differentiating GD from other causes of thyrotoxicosis in a real-world sample of patients with active thyrotoxicosis. In combination, both tests showed little benefit compared with the TBII assay alone. Thyrotropin receptor antibody assay results should be carefully interpreted in patients with mild GD or longstanding disease.

Educational adaptation to clinical training during the COVID-19 pandemic: a process analysis.

BACKGROUND: The COVID-19 pandemic is unprecedented in terms of the extent and rapidity of the disruption forced upon formal clinical education, most notably the extensive transition of clinical skills learning to interactive video-based clinical education. METHODS: In a phenomenologic study, we used thematic analysis to explore the COVID-19 disruption to clinical training and understand processes relating to adaptation in a large academic medical center. We conducted semi-structured interviews with 14 clinical teachers and 16 trainees representing all levels of clinical learning. Interviews occurred within the initial three months of the crisis, and data were analyzed following a thematic analysis coding process. RESULTS: We constructed eight themes synthesizing our participants' perceptions of the immediate unanticipated disruption, noting in the process their alignment with a change management framework. These included: urgency in adapting, with an obvious imperative for change; overcoming inconsistent involvement and support through the formation of self-organized frontline coalitions; attempts to develop strategy and vision via initially reactive but eventually consistent communication; empowering a volunteer army through co-creation and a flattened hierarchy; and efforts to sustain improvement and positive momentum with celebration of trial, error, and growth. The majority of participants found positive outcomes resulting from the tumultuous change process. Moreover, they were now more readily accepting of change, and tolerant of the ambiguous and iterative nature inherent in the education change process. Many anticipated that some innovation would, or would at least deserve to, continue post- crisis. CONCLUSIONS: The COVID-19 pandemic afforded an opportunity to study the content and process of change during an active crisis. In this case of clinical education, our findings provide insight into the ways an academic medical system adapts to unanticipated circumstances. We found alignment with broader organizational change management models and that, compared with crisis management models (and their shorter term focus on resolving such crises), stakeholders self-organized in a reliable manner that carries the potential advantage of preserving such beneficial change.

Optimizing allocation of curricular content across the Undergraduate & Graduate Medical Education Continuum.

BACKGROUND: Medical educators struggle to incorporate socio-cultural topics into crowded curricula. The "continuum of learning" includes undergraduate and graduate medical education. Utilizing an exemplar socio-cultural topic, we studied the feasibility of achieving expert consensus among two groups of faculty (experts in medical education and experts in social determinants of health) on which aspects of the topic could be taught during undergraduate versus graduate medical education. METHODS: A modified Delphi method was used to generate expert consensus on which learning objectives of social determinants of health are best taught at each stage of medical education. Delphi respondents included experts in medical education or social determinants of health. A survey was created using nationally published criteria for social determinants of health learning objectives. Respondents were asked 1) which learning objectives were necessary for every physician (irrespective of specialty) to develop competence upon completion of medical training and 2) when the learning objective should be taught. Respondents were also asked an open-ended question on how they made the determination of when in the medical education continuum the learning objective should be taught. RESULTS: 26 out of 55 experts (13 social determinants of health and 13 education experts) responded to all 3 Delphi rounds. Experts evaluated a total of 49 learning objectives and were able to achieve consensus for at least one of the two research questions for 45 of 49 (92%) learning objectives. 50% more learning objectives reached consensus for inclusion in undergraduate (n = 21) versus graduate medical education (n = 14). CONCLUSIONS: A modified Delphi technique demonstrated that experts could identify key learning objectives of social determinants of health needed by all physicians and allocate content along the undergraduate and graduate medical education continuum. This approach could serve as a model for similar socio-cultural content. Future work should employ a qualitative approach to capture principles utilized by experts when making these decisions.

Role of Sonographic Characteristics of Thyroid Bed Lesions Identified Following Thyroidectomy in the Diagnosis or Exclusion of Recurrent Cancer.

Background US of the thyroid bed in patients with thyroid cancer often depicts small lesions, but it is unclear whether US characteristics of lesions can help predict cancer recurrence. Purpose To determine whether size or US features of lesions in the thyroid bed after thyroidectomy in conjunction with clinical features can help predict thyroid cancer recurrence. Materials and Methods With use of a US reporting database, all patients imaged between July 2006 and June 2016 with an indication of post-thyroidectomy follow-up were retrospectively identified. Recorded data included patient demographic characteristics; date of thyroidectomy; thyroid cancer type; presence, size, and US characteristics of thyroid bed lesions; and results of fine-needle aspiration (FNA). Images were reviewed for lesions that underwent FNA. The Fisher exact test was used for analysis. Results A total of 1885 patients (mean age ± standard deviation, 48 years ± 15; 1493 female patients) underwent 5732 US examinations. Most patients (1541 of 1885 [82%]) had papillary cancer. Overall, 3163 thyroid bed lesions were reported in 5732 US examinations (40.4%). More than half of these lesions (1860 of 3163 [58.8%]) had a maximum measurement of 6 mm or greater. FNA was performed in 144 of the 3163 lesions (4.6%), of which 61 (42.4%) were malignant, 33 (22.9%) were benign, and 50 (34.7%) were nondiagnostic. Five nondiagnostic lesions eventually proved malignant. Only the presence of punctate echogenicities in the lesion (28 of 61 malignant lesions [45.9%]; three of 33 benign lesions [9%]; 12 of 50 nondiagnostic lesions [24%]; P < .001) or the history of positive lymph nodes at thyroidectomy (44 of 61 malignant lesions [72.1%]; 10 of 33 benign lesions [30%]; 19 of 50 nondiagnostic lesions [38%]; P < .001) were associated with malignancy. Of 3019 thyroid bed lesions that did not undergo FNA, three were malignant and 2248 showed no growth at follow-up US ranging from 6 months to 10 years and are presumed benign. Of the 1303 lesions smaller than 6 mm, only two (0.2%) were malignant. Conclusion Small lesions are commonly found in the thyroid bed after thyroidectomy, and most are likely to be benign. Lesions smaller than 6 mm with no punctate echogenicities had a minimal risk for malignancy. © RSNA, 2021 See also the editorial by Grant and Malhi in this issue.

Completion Thyroidectomy is Less Common Following Updated 2015 American Thyroid Association Guidelines.

BACKGROUND: The 2015 American Thyroid Association (ATA) guidelines recommended that low-risk, differentiated thyroid cancers (DTC) between 1 and 4 cm may be treated with thyroid lobectomy alone. We sought to determine the effect of these guideline changes on the rate of completion thyroidectomy (CT) for low-risk DTC and factors influencing surgical decision-making. METHODS: All patients from 2014 to 2018 who received an initial thyroid lobectomy at our institution with final pathology demonstrating DTC were included. Patients were divided into "pre" and "post" guideline cohorts (2014-2015 and 2016-2018, respectively). The rate of CT was compared between the two cohorts. Patient demographics and tumor characteristics were examined for association with CT. RESULTS: A total of 163 patients met study criteria: 63 patients in the 2014-2015 ("pre") and 100 in the 2016-2018 ("post") group. In the "pre" period, 41 (65.1%) patients received CT compared with 43 (43.0%) in the "post" period (p < 0.01)-a 34% decrease in the rate of completion surgery (p < 0.01). Of low-risk patients with DTC between 1 and 4 cm in size, 17 of 35 (48.6%) received CT in the "pre" period compared with 15 of 60 (25.0%) in the post period-a 48.6% decrease in the rate of completion surgery (p = 0.02). Greater tumor size, capsular invasion, and multifocality were associated with CT in low-risk "post" guideline patients (p < 0.05 for all). CONCLUSIONS: The rate of CT decreased significantly by 48.6% for low-risk patients with DTC between 1 and 4 cm, demonstrating recognition of the 2015 ATA guidelines. However, 25% of these patients underwent CT, suggesting additional factors influencing the decision for further treatment.

A potential diagnostic pitfall for hobnail variant of papillary thyroid carcinoma.

AIMS: Hobnail variant of papillary thyroid carcinoma (PTC) is an aggressive PTC subtype characterised by a hobnail cytomorphology. However, some classic PTC have a 'hobnail-like' cytomorphology associated with thick, hyalinised, variably oedematous fibrovascular cores that appears to be a form of ischaemic/degenerative atypia. METHODS AND RESULTS: We studied three cohorts to compare the histopathological characteristics and clinical outcome of 'hobnail-like' classic PTC and true hobnail variant of PTC: cohort 1, PTC consecutively resected between 2016 and 2017 (to assess frequency of 'hobnail-like' cytomorphology); cohort 2, 20 'hobnail-like' classic PTC resected between 2005 and 2007 (to assess clinical outcome); and cohort 3, seven true hobnail variant of PTC. A 'hobnail-like' cytomorphology was identified in 16% of consecutively resected PTC. Compared with true hobnail variant, 'hobnail-like' classic PTC occurred in younger patients (mean age 40 years versus 68 years, P < 0.001), were smaller tumours (mean tumour size 2.1 cm versus 4.4 cm, P < 0.001), had a lower rate of gross extrathyroidal extension (0% versus 71%, P < 0.001), had a lower proliferative rate (≥3 mitoses per 10 high-power fields seen in 0% versus 71%, P < 0.001; Ki67 index ≥5% in 0% versus 86%, P < 0.001), a lower rate of secondary pathogenic mutations (for cases with molecular data, 0% versus 100%, P = 0.0061) and improved survival (for cases with sufficient clinical outcome data, 10-year disease-free survival of 93% versus 0%, P = 0.0016). CONCLUSION: Classic PTC can show ischaemic/degenerative atypia that mimics the hobnail cytomorphology of true hobnail variant; however, these tumours lack aggressive histopathological features and pursue an indolent clinical course.

Effect of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP) on Malignancy Rates in Thyroid Nodules: How to Counsel Patients on Extent of Surgery.

PURPOSE: To investigate the impact of the nomenclature change to "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) on reported malignancy rates following thyroidectomy. METHODS: Retrospective cohort study of patients with thyroid nodules sampled preoperatively with fine-needle aspiration (FNA) and subsequently removed at one tertiary-care hospital from 4/2016 to 2/2017. Surgical procedure, anatomic pathology, thyroid cytopathology classification, and demographic characteristics were recorded. RESULTS: Thyroidectomy was performed in 353 patients. Twenty-six patients (7.3%) had NIFTP on anatomic pathology. Preoperative FNA demonstrated atypia of undetermined significance (AUS/Bethesda III) in 13 (50%), suspicious for malignancy (SUS/Bethesda V) in 6 (23%), suspicious for follicular neoplasm (SFN/Bethesda IV) in 4 (15%), benign/Bethesda I in 2 (8%), and malignant/Bethesda VI in 1 (4%). Invasive malignancy rates across cytologic categories changed as follows: benign (n = 74) from 4 to 1%, AUS (n = 85) from 33 to 18% (p < 0.05), SFN (n = 58) from 29 to 22%, SUS (n = 33) from 91 to 73% (p < 0.05), and malignant (n = 99) from 99 to 98%. Overall decrease in invasive malignancy was 7.3% for the entire population and 13.1% for indeterminate preoperative FNA cytology (Bethesda III-V). Among 26 NIFTP patients, 17 had thyroid lobectomy (TL) and 9 underwent total thyroidectomy (TT). Eight of the nine patients with TT could have been definitively treated with TL, an 89% decrease. CONCLUSIONS: The NIFTP nomenclature change led to an overall decrease in the malignancy rate at our institution, especially for Bethesda III-V categories. Patients may be counseled toward more conservative surgical options if NIFTP is in the differential.

Reasons Associated with Total Thyroidectomy as Initial Surgical Management of an Indeterminate Thyroid Nodule.

BACKGROUND: Diagnostic hemithyroidectomy (HT) is the most widely recommended surgical procedure for a nodule with indeterminate cytology; however, additional details may make initial total thyroidectomy (TT) preferable. We sought to identify patient-specific factors (PSFs) associated with initial TT in patients with indeterminate thyroid nodules. METHODS: Retrospective analysis of all patients with a thyroid nodule ≥ 1 cm and initial cytology of atypia of undetermined significance or suspicious for follicular neoplasm between 2012 and 2015 who underwent thyroidectomy. Medical records were reviewed for patient demographics, neck symptoms, nodule size, cytology, molecular test results, final histopathology, and additional PSFs influencing surgical management. Variables were analyzed to determine associations with the use of initial TT. Logistic regression analyses were performed to identify independent associations. RESULTS: Of 325 included patients, 182/325 (56.0%) had HT and 143/325 (44.0%) had TT. While patient age and sex, nodule size, and cytology result were not associated with initial treatment, five PSFs were associated with initial TT (p < 0.0001). These included contralateral nodules, hypothyroidism, fluorodeoxyglucose avidity on positron emission tomography scan, family history of thyroid cancer, and increased surgical risk. At least one PSF was present in 126/143 (88.1%) TT patients versus 47/182 (25.8%) HT patients (p < 0.0001). Multivariate logistic regression analysis demonstrated that these variables were the strongest independent predictor of TT (odds ratio 45.93, 95% confidence interval 18.80-112.23, p < 0.001). CONCLUSIONS: When surgical management of an indeterminate cytology thyroid nodule was performed, several PSFs were associated with a preference by surgeons and patients for initial TT, which may be useful to consider in making decisions on initial operative extent.

POSITIVE THYROTROPIN RECEPTOR ANTIBODIES IN PATIENTS WITH TRANSIENT THYROTOXICOSIS.

OBJECTIVE: Thyrotropin (TSH) receptor antibody (TRAb) testing is considered accurate for the diagnosis of Graves disease (GD) and has been identified rarely in thyrotoxic patients without GD. We describe 4 patients with transient thyrotoxicosis and positive TRAb to highlight this clinical possibility. METHODS: Patient demographics, symptoms, laboratory findings, and time to resolution of thyrotoxicosis are summarized. TRAb testing was performed by either a third-generation thyrotropin-binding inhibitory immunoglobulin (TBII) competitive-binding assay or a thyroid-stimulating immunoglobulin (TSI) bioassay from either Mayo Clinic Laboratory or Quest Diagnostics. RESULTS: Four patients with transient thyrotoxicosis and positive TRAb testing were identified. Of these, three were female, and the median age was 44 years (range, 25 to 49 years). Median symptom duration at evaluation was 6.5 weeks (range, 3 to 12 weeks). No patient had any clinical manifestations unique to GD or exposure to biotin, thyroid hormone, supplements, iodine, or relevant medications. The TSH was <0.1 mIU/L in all patients. Three patients had a positive TSI, which was elevated less than twice the upper limit of the reference range in all cases, and 1 patient had a strongly positive TBII. None of the patients were treated with thionamides or radioactive iodine. Spontaneous resolution occurred in all patients at a median of 5.5 weeks (range, 2 to 14.4 weeks). CONCLUSION: These cases demonstrate that TSI or TBII may be present in thyrotoxic patients with transient thyrotoxicosis. For clinically stable patients presenting without pathognomonic evidence of GD, mildly elevated TRAb results may require cautious interpretation, and alterative diagnostic testing or close monitoring should be considered. ABBREVIATIONS: cAMP = cyclic adenosine monophosphate; FT4 = free thyroxine; GD = Graves disease; TBII = thyrotropin-binding inhibitory immunoglobulin (also known as TBI); TRAb = thyrotropin receptor antibody; TSH = thyrotropin; TSHR = thyrotropin receptor; TSI = thyroid-stimulating immunoglobulin; TT3 = total triiodothyronine; TT4 = total thyroxine.

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 .

Preoperative diagnosis of benign thyroid nodules with indeterminate cytology.

BACKGROUND: Approximately 15 to 30% of thyroid nodules evaluated by means of fine-needle aspiration are not clearly benign or malignant. Patients with cytologically indeterminate nodules are often referred for diagnostic surgery, though most of these nodules prove to be benign. A novel diagnostic test that measures the expression of 167 genes has shown promise in improving preoperative risk assessment. METHODS: We performed a 19-month, prospective, multicenter validation study involving 49 clinical sites, 3789 patients, and 4812 fine-needle aspirates from thyroid nodules 1 cm or larger that required evaluation. We obtained 577 cytologically indeterminate aspirates, 413 of which had corresponding histopathological specimens from excised lesions. Results of a central, blinded histopathological review served as the reference standard. After inclusion criteria were met, a gene-expression classifier was used to test 265 indeterminate nodules in this analysis, and its performance was assessed. RESULTS: Of the 265 indeterminate nodules, 85 were malignant. The gene-expression classifier correctly identified 78 of the 85 nodules as suspicious (92% sensitivity; 95% confidence interval [CI], 84 to 97), with a specificity of 52% (95% CI, 44 to 59). The negative predictive values for "atypia (or follicular lesion) of undetermined clinical significance," "follicular neoplasm or lesion suspicious for follicular neoplasm," or "suspicious cytologic findings" were 95%, 94%, and 85%, respectively. Analysis of 7 aspirates with false negative results revealed that 6 had a paucity of thyroid follicular cells, suggesting insufficient sampling of the nodule. CONCLUSIONS: These data suggest consideration of a more conservative approach for most patients with thyroid nodules that are cytologically indeterminate on fine-needle aspiration and benign according to gene-expression classifier results. (Funded by Veracyte.).

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.

False negative cytology in large thyroid nodules.

BACKGROUND: Controversy exists regarding the accuracy of fine-needle aspiration (FNA) in large thyroid nodules. Recent surgical series have documented false-negative rates ranging from 0.7 to 13 %. We examined the accuracy of benign FNA cytology in patients with thyroid nodules ≥3 cm who underwent surgical resection and identified features characteristic of false-negative results. METHODS: We retrospectively studied all thyroidectomy specimens between January 2009 and October 2011 and identified nodules ≥3 cm with corresponding benign preoperative FNA cytology. We collected clinical information regarding patient demographics, nodule size, symptoms, sonographic features, FNA results, and final surgical pathology. For comparison, we analyzed nodules <3 cm from this cohort also with benign FNA cytology. RESULTS: A total of 323 nodules with benign preoperative cytology were identified. Eighty-three nodules were <3 cm, 94 nodules were 3-3.9 cm, and 146 nodules were ≥4 cm in size. The false-negative rate was 11.7 % for all nodules ≥3 cm and 4.8 % for nodules <3 cm (p = 0.03). Subgroup analysis of nodules ≥3 cm revealed a false-negative rate of 12.8 % for nodules 3-3.9 cm and 11 % for nodules ≥4 cm. Age ≥55 years and asymptomatic clinical status were the only patient characteristics that reached statistical significance as risk factors. Final pathology of the false-negative specimens consisted mainly of follicular variant of papillary thyroid cancer and follicular thyroid cancer. CONCLUSIONS: When referred for thyroidectomy, patients with large thyroid nodules demonstrate a modest, yet significant, false-negative rate despite initial benign aspiration cytology. Therefore, thyroid nodules ≥3 cm may be considered for removal even when referred with benign preoperative cytology.

Textual analysis of internal medicine residency personal statements: themes and gender differences.

CONTEXT: Applicants to US residency training programmes are required to submit a personal statement, the content of which is flexible but often requires them to describe their career goals and aspirations. Despite their importance, no systematic research has explored common themes and gender differences inherent to these statements. OBJECTIVES: This study was conducted to analyse US applicants' Electronic Residency Application Service (ERAS) personal statements using two automated textual analysis programs, and to assess for common themes and gender-associated differences. METHODS: A retrospective cohort study of 2138 personal statements (containing 1,485,255 words) from candidates from 377 national and international medical schools applying to US internal medicine (IM) residency programmes through ERAS was conducted. A mathematical analysis of text segments using a recursive algorithm was performed; two different specifications of the text segments were used to conduct an internal validation. RESULTS: Five statistically significant thematic classes were identified through independent review by the researchers. These were best defined as referring to: the appeal of the residency programme; memorable patients; health care as public policy; research and academia, and family inspiration. Some themes were common to all applications. However, important gender-specific differences were identified. Notably, men were more likely to describe personal attributes and to self-promote, whereas women more frequently expressed the communicative and team-based aspects of doctoring. The results were externally validated using a second software program. Although these data comprise part of the national pool, they represent applicants to a single specialty at a single institution. CONCLUSIONS: By applying textual analysis to material derived from a national cohort, we identified common narrative themes in the personal statements of future US physicians, noting differences between men and women. Together, these data provide novel insight into the dominant discourse of doctoring in this generation of students applying for further training in US IM residency programmes, and depict a diverse group of applicants with multiple motivations, desires and goals. Furthermore, differences seen between men and women add to the growing understanding of bias in medical education. Training programmes may benefit by adapting curricula to foster such diverse interests.

Sonographic appearance of thyroid cancer in patients with Hashimoto thyroiditis.

OBJECTIVES: To determine whether the sonographic appearance of thyroid cancer differs in patients with and without Hashimoto thyroiditis. METHODS: Patients with histologically proven thyroid cancer who had thyroid peroxidase (TPO) antibodies measured and sonography performed preoperatively were included. We evaluated each nodule for size, echogenicity, composition, margins, halo, and vascularity and evaluated the background heterogeneity of the gland. RESULTS: There were 162 thyroid cancers in 145 patients. Forty-two patients (29.0%) had Hashimoto thyroiditis with positive TPO antibodies, and 103 patients (71.0%) had negative TPO antibodies. The background echogenicity was more often heterogeneous in TPO antibody-positive patients compared to those who had negative TPO antibodies (57.1% versus 26.2%; P= .0005). Comparing cancers in TPO antibody-positive to TPO antibody-negative patients, there was no significant difference in the size, echogenicity, composition, margins, halo presence, calcification presence and type, or vascularity of the cancerous nodule (P > .05). Among TPO antibody-positive patients, comparing thyroid cancerous nodules in patients with heterogeneous glands to those with homogeneous glands, there was no significant difference in any sonographic characteristic except the margin of the nodule, which was more often irregular or poorly defined in heterogeneous glands and more often smooth in homogeneous glands (P< .05). CONCLUSIONS: Sonographic features of thyroid cancer are similar in patients with and without Hashimoto thyroiditis. Among patients with Hashimoto thyroiditis and thyroid cancer, the sonographic appearance of the cancerous nodule is similar, except that cancerous nodule margins are more likely to be irregular or poorly defined when the gland is heterogeneous.

Length of attending-student and resident-student interactions in the inpatient medicine clerkship.

UNLABELLED: PHENOMENON: Changes in the medical education milieu have led away from the apprenticeship model resulting in shorter physician-student interactions. Faculty and student feedback suggests that supervisor/student interactions may now be more cursory with increasing numbers of supervisors per student, and shorter duration of interaction. This may affect both education and student assessment. APPROACH: We compared inpatient attending and resident daily schedules with those of 3rd- and 4th-year medical students rotating on medicine clerkships at Brigham and Women's Hospital during academic years 2009-11 to determine the number of days of overlap. We used evaluation forms to determine the extent of evaluator's self-reported knowledge of the student. FINDINGS: We correlated the daily schedules of 199 students and 204 resident and 187 attending physicians, which resulted in 558 resident-student pairings and 680 attending-student pairings over 2 years. During a 4-week block, students averaged 3.7 attending physicians (M = 4, range = 2-7), with 49.7% supervised by 4 or more. Attending-student overlap averaged 9 days (M = 9, range = 2-23), though 40% were 7 days or less. Students overlapped with an average 3.4 residents (M = 3, range = 1-6). Resident-student overlap averaged 12 days (M = 11, range = 3-26). There were 824 student assessment forms analyzed. Resident and attending physician supervisors describing knowledge of their student as "good/average" overlapped with students for 14 and 11 days respectively compared to resident and physician supervisors who described their knowledge as "poor" (11 days, p < .01; 6 days, p < .01). Insights: On the inpatient medicine clerkship, students have multiple supervising physicians with wide variability in the period of overlap. This leads to a disrupted apprenticeship model with fragmentation of supervision and concomitant effects on assessment, feedback, role modeling, and clerkship education.

How are childhood thyroid nodules discovered: opportunities for improving early detection.

In a retrospective analysis of childhood thyroid nodules, 18% were radiographic incidentalomas and 41% were discovered by a clinician's palpation; 40% were discovered by patients' families. The latter group had the largest nodules and highest rates of thyroid cancer metastasis, suggesting opportunities for earlier detection through annual well-child visits.

A prospective assessment defining the limitations of thyroid nodule pathologic evaluation.

BACKGROUND: Clinical management of thyroid neoplasms is based on light microscopic diagnosis, but its accuracy and precision are poorly defined. OBJECTIVE: To assess inter- and intraobserver variability of preoperative cytopathologic and postoperative histopathologic thyroid diagnoses. DESIGN: Samples were collected in a prospective, multicenter trial validating a gene expression classifier between June 2009 and December 2010. SETTING: 14 academic and 35 community clinical sites. PATIENTS: 653 patients with 776 surgically resected thyroid nodules of 1 cm or greater. MEASUREMENTS: Intraobserver concordance among 2 or more central histopathologists who independently read histopathology slides was calculated. Interobserver concordance between the diagnoses made by the central histopathologists and those made by local pathologists were calculated. Intra- and interobserver concordance for cytopathology was similarly calculated by comparing diagnoses made by local pathologists with those made by a central panel of 3 cytopathologists. RESULTS: Concordance on the histopathologic distinction between benign and malignant diagnoses was 91% comparing local with central histopathologists and 90% comparing 2 central histopathologists. Using the 6-category Bethesda System, 64.0% of diagnoses made by local and central cytopathologists and 74.7% of intraobserver diagnoses were concordant. Central cytopathologists made fewer indeterminate diagnoses than local pathologists (41.2% vs. 55.0%). LIMITATIONS: Many local pathologists did not use the Bethesda System, so their reports were translated to allow comparison. The study required histopathology, and the study population and specimens did not encompass all newly evaluated patients with a thyroid nodule. CONCLUSION: Substantial inter- and intraobserver variability exists in the cytopathologic and histopathologic evaluation of thyroid nodules, confirming an inherent limitation of visual microscopic diagnosis. PRIMARY FUNDING SOURCE: Veracyte.

Nonoperative, Active Surveillance of Larger Malignant and Suspicious Thyroid Nodules.

CONTEXT: Active surveillance for papillary thyroid cancer (PTC) meeting criteria for surgical resection is uncommon. Which patients may prove reasonable candidates for this approach is not well defined. OBJECTIVE: This work aimed to examine the feasibility and safety of active surveillance for patients with known or suspected intrathyroidal PTC up to 4 cm in diameter. METHODS: A retrospective review was conducted of all consecutive patients who underwent nonoperative active surveillance of suspicious or malignant thyroid nodules over a 20-year period from 2001 to 2021. We included patients with an initial ultrasound-fine-needle aspiration confirming either (a) Bethesda 5 or 6 cytology or (b) a "suspicious" Afirma molecular test. The primary outcomes and measures included the rate of adverse oncologic outcomes (mortality and recurrence), as well as the cumulative incidence of size/volume growth. RESULTS: Sixty-nine patients were followed with active surveillance for 1 year or longer (average 55 months), with 26 patients (38%) having nodules 2 cm or larger. No patients were found to develop new-incident occurrence of lymph node or distant metastasis. One patient, however, demonstrated concern for progression to a dedifferentiated cancer on repeat core biopsy 17 years after initial start of nonoperative selection. A total of 21% of patients had an increase in maximum diameter more than 3 mm, while volume increase of 50% or greater was noted in 25% of patients. Thirteen patients ultimately underwent delayed (rescue) surgery, and no disease recurrence was noted after such treatment. Age and initial nodule size were not predictors of nodule growth. CONCLUSION: These data expand consideration of active surveillance of PTC in select patients with intrathyroidal suspected malignancy greater than 1 cm in diameter. Rescue surgery, if required at a later time point, appears effective.