Association of DNA Promoter Methylation and BRAF Mutation in Thyroid Cancer.

The BRAF V600E mutation and DNA promoter methylation play important roles in the pathogenesis of thyroid cancer (TC). However, the association of these genetic and epigenetic alterations is not clear. In this study, using paired tumor and surrounding normal tissue from the same patients, on a genome-wide scale we tried to identify (a) any association between BRAF mutation and DNA promoter methylation, and (b) if the molecular findings may provide a basis for therapeutic intervention. We included 40 patients with TC (female = 28, male = 12) without distant metastasis. BRAF mutation was present in 18 cases. We identified groups of differentially methylated loci (DML) that are found in (a) both BRAF mutant and wild type, (b) only in BRAF mutant tumors, and (c) only in BRAF wild type. BRAF mutation-specific promoter loci were more frequently hypomethylated, whereas BRAF wild-type-specific loci were more frequently hypermethylated. Common DML were enriched in cancer-related pathways, including the mismatch repair pathway and Wnt-signaling pathway. Wild-type-specific DML were enriched in RAS signaling. Methylation status of checkpoint signaling genes, as well as the T-cell inflamed genes, indicated an opportunity for the potential use of PDL1 inhibitors in BRAF mutant TC. Our study shows an association between BRAF mutation and methylation in TC that may have biological significance.

Scarless Surgery: Clinical Indications for Transoral Endocrine Surgery and Implications for Pathologists.

Transoral endocrine surgery (TES) is a scarless approach to thyroidectomy and parathyroidectomy for well-selected patients. Criteria for the TES approach to thyroidectomy include thyroid diameter less than or equal to 10 cm, benign nodule less than or equal to 6 cm, or confirmed or suspected malignant nodule less than or equal to 2 cm. Although fragmentation of surgical specimens has been reported in TES, additional studies are needed to evaluate the implications of TES on pathologic examination.

One hundred and one consecutive transoral endoscopic parathyroidectomies via the vestibular approach for PHPTH: a worldwide multi-institutional experience.

IMPORTANCE: The transoral vestibular approach for thyroid and parathyroid surgery is being adopted rapidly world-wide. Currently there is a paucity of information on this approach for primary hyperparathyroidism (PHPTH). If this approach is safe and efficacious it would provide patients a completely scarless option for parathyroidectomy. OBJECTIVE: To determine whether parathyroidectomy via the transoral vestibular approach can be successfully done in a safe and efficient manner. DESIGN: Consecutive case series of 101 transoral parathyroidectomies performed over a two-year period. SETTING: Multi-institutional, academic, high-volume transoral thyroidectomy centers from the USA, Israel, and Thailand. PARTICIPANTS: A consecutive series of adult patients with a biochemical diagnosis of classic PHPTH and who met criteria for parathyroidectomy based on established international consensus for surgery for PHPTH. All patients also had well-localized single adenomas on at least two preoperative imaging studies. INTERVENTION: Transoral endoscopic parathyroidectomy vestibular approach. MAIN OUTCOMES AND MEASURES: Surgical success rate defined by immediate intra or post-operative return to normal PTH values. Surgical complications including recurrent laryngeal nerve injury, permanent hypoparathyroidism, and infection. RESULTS: Of the 101 consecutive transoral parathyroidectomy patients 84% were female with an average age of 54.23 ± 11.0 years and an average BMI of 27.35 ± 6.19. Ninety-nine out of the 101 patients had immediate return to normal PTH after resection for a surgical success rate of 98%. There were no permanent recurrent laryngeal nerve injuries, one temporary nerve palsy, and no permanent hypoparathyroidism. The median operative time dropped from 130.5 min (IQR 86) to 66.5 min (IQR 56) between the first- and second-half of cases. CONCLUSION AND RELEVANCE: Transoral endoscopic parathyroidectomy via the vestibular approach is a scarless method of removing parathyroids that is clinically feasible, safe, and efficacious and is a reasonable option for focused minimally invasive parathyroidectomy that can be offered to select patients with PHPTH.

Clinical Translation and Evaluation of a Handheld and Biocompatible Mass Spectrometry Probe for Surgical Use.

BACKGROUND: Intraoperative tissue analysis and identification are critical to guide surgical procedures and improve patient outcomes. Here, we describe the clinical translation and evaluation of the MasSpec Pen technology for molecular analysis of in vivo and freshly excised tissues in the operating room (OR). METHODS: An Orbitrap mass spectrometer equipped with a MasSpec Pen interface was installed in an OR. A "dual-path" MasSpec Pen interface was designed and programmed for the clinical studies with 2 parallel systems that facilitated the operation of the MasSpec Pen. The MasSpec Pen devices were autoclaved before each surgical procedure and were used by surgeons and surgical staff during 100 surgeries over a 12-month period. RESULTS: Detection of mass spectral profiles from 715 in vivo and ex vivo analyses performed on thyroid, parathyroid, lymph node, breast, pancreatic, and bile duct tissues during parathyroidectomies, thyroidectomies, breast, and pancreatic neoplasia surgeries was achieved. The MasSpec Pen enabled gentle extraction and sensitive detection of various molecular species including small metabolites and lipids using a droplet of sterile water without causing apparent tissue damage. Notably, effective molecular analysis was achieved while no limitations to sequential histologic tissue analysis were identified and no device-related complications were reported for any of the patients. CONCLUSIONS: This study shows that the MasSpec Pen system can be successfully incorporated into the OR, allowing direct detection of rich molecular profiles from tissues with a seconds-long turnaround time that could be used to inform surgical and clinical decisions without disrupting tissue analysis workflows.

Public Perceptions of Transoral Endocrine Surgery and their Influence on Choice of Operative Approach.

BACKGROUND: Transoral Endocrine Surgery (TES) represents an alternative to the open approach with no visible scar. Studies have shown TES has a safety profile similar to the open approach, but adoption has been limited. Public perception and preference for TES are factors associated with adoption that have not been explored. Here we aim to understand the perception of TES by the public and factors which influence decision making. MATERIALS AND METHODS: A 38-question survey was designed to assess factors which influence willingness to pursue TES. The survey was distributed utilizing Amazon Mechanical Turk (MTurk), a crowdsourcing marketplace in which individuals perform tasks virtually based on interest. Descriptive analyses, Pearson chi-squared tests, Student's t-tests, and multivariate logistic regression were performed to evaluate theoretical decision to pursue TES. RESULTS: Respondents (n = 795) were 47% female, 78% white, 70% held a college degree or higher, and had a mean age of 37. The majority (69%) preferred a mouth incision over a neck incision. Respondents were willing to pursue TES for a theoretical cancer despite increased cost (52%) and longer operative time (70%). Respondents top two most important surgical factors were safety and experience. CONCLUSIONS: Our data suggest the general public is willing to pursue TES and factors thought to be barriers to choosing TES may not deter the public. An informed discussion with appropriately-selected patients should be had between the patient and surgeon regarding specific surgical and postoperative differences including risks, safety, and experience.

Preferences for thyroidectomy technique: Comparing traditional and transoral approaches.

BACKGROUND: We investigated preferences between the transcervical and transoral thyroidectomy approach in the United States and Israel. METHODS: An online survey assessing scar attitudes and surgical preferences, in English and Hebrew, was distributed on ThyCa.com and other platforms. RESULTS: 928 and 339 responses from the United States and Israel cohorts, respectively, were analyzed. In both countries, individuals without prior thyroidectomy preferred a scarless approach when hypothetical risks equaled those of traditional thyroidectomy (77% United States, 76% Israel, p = 0.61). U.S. respondents without thyroidectomy had greater preference to avoid a scar and would pay more to do so than those with thyroidectomy (both p < 0.001). Many respondents with prior thyroidectomy still expressed interest in scarless alternatives (57% United States). CONCLUSIONS: Populations in Israel and the United States prefer scarless thyroidectomy when risks equal the traditional approach. While individuals without prior thyroidectomy are more likely to favor a scarless option, former thyroidectomy patients may have preferred avoiding a scar.

Current status of robotic adrenalectomy in the United States.

Since its introduction more than 30 years ago, laparoscopic adrenalectomy has become the gold standard approach to adrenal surgery for the majority of adrenal pathology. It has been shown to have superior clinical benefits to open adrenalectomy for the majority of cases of adrenal surgery. Robot-assisted adrenalectomy has also been shown to be a reasonable alternative approach to adrenal gland resection. Even though robot-assisted adrenalectomy has been performed in the United States for more than 20 years, it has yet to become the gold-standard for this operation, evidenced by the fact that in the United States laparoscopic adrenalectomy remains more common than robot-assisted adrenalectomy. Market factors, clinical factors and surgeon factors all play a role in the spread and adoption of robotic surgery in general. Here we review the most up to date literature on the state of robotic adrenalectomy in the United States, and explore some of the factors that may be influencing the rate of adoption of robotic adrenalectomy in the United States.

Localization of Parathyroid Disease in Reoperative Patients with Primary Hyperparathyroidism.

The localization of persistent or recurrent disease in reoperative patients with primary hyperparathyroidism presents challenges for radiologists and surgeons alike. In this article, we summarize the relevant imaging modalities, compare their accuracy in identifying reoperative disease, and outline their advantages and disadvantages. Accurate localization by preoperative imaging is a predictor of operative success, whereas negative or discordant preoperative imaging is a risk factor for operative failure. Ultrasound is a common first-line modality because it is inexpensive, accessible, and radiation-free. However, it is highly operator-dependent and less accurate in the reoperative setting than in the primary setting. Sestamibi scintigraphy is superior to ultrasound in localizing reoperative disease but requires radiation, prolonged imaging times, and reader experience for accurate interpretation. Like ultrasound, sestamibi scintigraphy is less accurate in the reoperative setting because reoperative patients can exhibit distorted anatomy, altered perfusion of remaining glands, and interference of radiotracer uptake. Meanwhile, four-dimensional computed tomography (4DCT) is superior to ultrasound and sestamibi scintigraphy in localizing reoperative disease but requires the use of radiation and intravenous contrast. Both 4DCT and magnetic resonance imaging (MRI) do not significantly differ in accuracy between unexplored and reoperative patients. However, MRI is more costly, inaccessible, and time-consuming than 4DCT and is inappropriate as a first-line modality. Hybrid imaging with positron emission tomography and computed tomography (PET/CT) may be a promising second-line modality in the reoperative setting, particularly when first-line modalities are discordant or inconclusive. Lastly, selective venous sampling should be reserved for challenging cases in which noninvasive modalities are negative or discordant. In the challenging population of reoperative patients with PHPT, a multimodality approach that utilizes the expertise of high-volume centers can accurately localize persistent or recurrent disease and enable curative parathyroidectomy.

Transoral endocrine surgery: Considerations for adopting a new technique.

Transoral endocrine surgery encompasses a group of operations whereby the thyroid or parathyroid gland is removed through the oral vestibule. This operation has the advantage of leaving no cutaneous scar and a risk profile similar to open surgery. Adoption of this technique has increased dramatically over the last several years. It is of paramount importance for surgeons to undergo adequate training before adopting this technique.

Analytical Differences in Intraoperative Parathyroid Hormone Assays.

BACKGROUND: We compared the rates of intraoperative parathyroid hormone (PTH) decline using the Siemens Immulite® Turbo PTH and Roche Elecsys® short turnaround time PTH assays in 95 consecutive surgical patients to investigate analytical and turnaround time (TAT) differences between the tests performed in the operating room (OR) vs the central clinical chemistry laboratory (CCL). METHODS: Serial blood samples from 95 patients undergoing parathyroidectomy were collected and measured using the 2 immunoassays. Specimens from the first 15 patients were measured simultaneously in the OR and CCL and used for the TAT study. In addition to 2 baseline samples, specimens were collected at 5, 10, and 15 min (for some patients, >15 min) after parathyroidectomy. RESULTS: In the TAT study, a significant difference was observed (OR median 20 min vs CCL median 27 min; P < 0.05). Of the 95 patient series, slower rates of parathyroid hormone decrease were observed in approximately 20% of the patients when comparing the Roche with the Immulite immunoassay. CONCLUSIONS: There was a slightly longer TAT in the CCL compared with running the assay directly within the OR (median difference of approximately 7 min). For a majority of the patients, both methods showed equivalent rates of PTH decline; however, for approximately 20% of the patients, there was a slower rate of PTH decline using the Roche assay.

The Importance of Family History in the Management of Endocrine Disease.

Family history is an essential component of the workup of endocrine surgery patients. The family history can change the diagnosis, management, and follow-up of endocrine patients. Here we discuss the importance of family history, review familial endocrine disorders, and develop a list of pertinent questions to ask when taking a family history of patients with endocrine disorders.

Patient Eligibility for Transoral Endocrine Surgery Procedures in the United States.

Importance: Transoral endocrine surgery (TES) allows thyroid and parathyroid operations to be performed without leaving any visible scar on the body. Controversy regarding the value of TES remains, in part owing to the common belief that TES is only applicable to a small, select group of patients. Knowledge of the overall applicability of these procedures is essential to understand the operation, as well as to decide the amount of effort and resources that should be allocated to further study the safety, efficacy, and value of these operations. Objective: To determine what percentage of US patients undergoing thyroid and parathyroid surgery are eligible for TES using currently accepted exclusion criteria. Design, Setting, and Participants: Cross-sectional study of 1000 consecutive thyroid and parathyroid operations (with or without neck dissection) performed between July 1, 2015, and July 1, 2018, at 3 high-volume academic US thyroid- and parathyroid-focused surgical practices (2 general surgery, 1 otolaryngology-head and neck endocrine surgery). Eligibility for TES was determined by retrospectively applying previously published exclusion criteria to the cases. Main Outcomes and Measures: The primary outcome was the percentage of thyroid and parathyroid cases eligible for TES. Secondary outcomes were a subgroup analysis of the percentage of specific types of cases eligible and the reasons for ineligibility. Results: The mean (SD) age of the 1000 surgical patients was 53 (15) years, mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 29 (7), and 747 (75.0%) of the patients were women. Five hundred fifty-eight (55.8%) of the patients were eligible for TES. Most patients with thyroid nodules with cytologically indeterminate behavior (165 of 217 [76.0%]), benign thyroid conditions (166 of 240 [69.2%]), and primary hyperparathyroidism (158 of 273 [57.9%]) were eligible for TES, but only 67 of 231 (29.0%) of patients with thyroid cancer were eligible. Among all 1000 cases reviewed, previous neck operation (97 of 441 [22.0%]), nonlocalized primary hyperparathyroidism (78 of 441 [17.7%]), and need for neck dissection (66 of 441 [15.0%]) were the most common reasons for ineligibility. Conclusions and Relevance: More than half of all patients undergoing thyroid and parathyroid surgery in this study were eligible for TES. This broad applicability suggests that a prospective multicenter trial is reasonable to definitively study the safety, outcomes, and cost of TES.

Failure to Diagnose and Treat Hyperparathyroidism Among Patients with Hypercalcemia: Opportunities for Intervention at the Patient and Physician Level to Increase Surgical Referral.

BACKGROUND: Hyperparathyroidism is both underdiagnosed and undertreated, but the reasons for these deficiencies have not been described. The purpose of this study was to identify reasons for underdiagnosis and undertreatment of hyperparathyroidism that could be addressed by targeted interventions. MATERIALS AND METHODS: We identified 3,200 patients with hypercalcemia (serum calcium >10.5 mg/dL) who had parathyroid hormone (PTH) levels evaluated at our institution from 2011 to 2016. We randomly sampled 60 patients and divided them into three groups based on their PTH levels. Two independent reviewers examined clinical notes and diagnostic data to identify reasons for delayed diagnosis or referral for treatment. RESULTS: The mean age of the patients was 61 ± 16.5 years, 68% were women, and 55% were white. Fifty percent of patients had ≥1 elevated calcium that was missed by their primary care provider. Hypercalcemia was frequently attributed to causes other than hyperparathyroidism, including diuretics (12%), calcium supplements (12%), dehydration (5%), and renal dysfunction (3%). Even when calcium and PTH were both elevated, the diagnosis was missed or delayed in 40% of patients. For 7% of patients, a nonsurgeon stated that surgery offered no benefit; 22% of patients were offered medical treatment or observation, and 8% opted not to see a surgeon. Only 20% of patients were referred for surgical evaluation, and they waited a median of 16 months before seeing a surgeon. CONCLUSION: To address common causes for delayed diagnosis and treatment of hyperparathyroidism, we must improve systems for recognizing hypercalcemia and better educate patients and providers about the consequences of untreated disease. IMPLICATIONS FOR PRACTICE: This study identified reasons why patients experience delays in workup, diagnosis, and treatment of primary hyperparathyroidism. These data provide valuable information for developing interventions that increase rates of diagnosis and referral.

Clinical Outcomes After Unilateral Adrenalectomy for Primary Aldosteronism.

Importance: In addition to biochemical cure, clinical benefits after surgery for primary aldosteronism depend on the magnitude of decrease in blood pressure (BP) and use of antihypertensive medications with a subsequent decreased risk of cardiovascular and/or cerebrovascular morbidity and drug-induced adverse effects. Objective: To evaluate the change in BP and use of antihypertensive medications within an international cohort of patients who recently underwent surgery for primary aldosteronism. Design, Setting, and Participants: A cohort study was conducted across 16 referral medical centers in Europe, the United States, Canada, and Australia. Patients who underwent unilateral adrenalectomy for primary aldosteronism between January 2010 and December 2016 were included. Data analysis was performed from August 2017 to June 2018. Unilateral disease was confirmed using computed tomography, magnetic resonance imaging, and/or adrenal venous sampling. Patients with missing or incomplete preoperative or follow-up data regarding BP or corresponding number of antihypertensive medications were excluded. Main Outcomes and Measures: Clinical success was defined based on postoperative BP and number of antihypertensive medications. Cure was defined as normotension without antihypertensive medications, and clear improvement as normotension with lower or equal use of antihypertensive medications. In patients with preoperative normotensivity, improvement was defined as postoperative normotension with lower antihypertensive use. All other patients were stratified as no clear success because the benefits of surgery were less obvious, mainly owing to postoperative, persistent hypertension. Clinical outcomes were assessed at follow-up closest to 6 months after surgery. Results: On the basis of inclusion and exclusion criteria, a total of 435 patients (84.6%) from a cohort of 514 patients who underwent unilateral adrenalectomy were eligible. Of these patients, 186 (42.3%) were women; mean (SD) age at the time of surgery was 50.7 (11.4) years. Cure was achieved in 118 patients (27.1%), clear improvement in 135 (31.0%), and no clear success in 182 (41.8%). In the subgroup classified as no clear success, 166 patients (91.2%) had postoperative hypertension. However, within this subgroup, the mean (SD) systolic and diastolic BP decreased significantly by 9 (22) mm Hg (P < .001) and 3 (15) mm Hg (P = .04), respectively. Also, the number of antihypertensive medications used decreased from 3 (range, 0-7) to 2 (range, 0-6) (P < .001). Moreover, in 75 of 182 patients (41.2%) within this subgroup, the decrease in systolic BP was 10 mm Hg or greater. Conclusions and Relevance: In this study, for most patients, adrenalectomy was associated with a postoperative normotensive state and reduction of antihypertensive medications. Furthermore, a significant proportion of patients with postoperative, persistent hypertension may benefit from adrenalectomy given the observed clinically relevant and significant reduction of BP and antihypertensive medications.

Preoperative calcitriol reduces postoperative intravenous calcium requirements and length of stay in parathyroidectomy for renal-origin hyperparathyroidism.

BACKGROUND: Patients undergoing subtotal parathyroidectomy for renal-origin hyperparathyroidism often develop postoperative hypocalcemia, requiring calcitriol and intravenous calcium (Postop-IVCa). We hypothesized that in subtotal parathyroidectomy for renal-origin hyperparathyroidism, preoperative calcitriol treatment reduces the use of postoperative administration of intravenous calcium. METHODS: A retrospective chart review compared subtotal parathyroidectomy for renal-origin hyperparathyroidism patients who received preoperative calcitriol treatment with those patietns who did not receive preoperative calcitriol treatment at one institution. Preoperative calcitriol treatment loading doses were 0.5 mcg twice daily for 5 days. All patients received postoperative calcitriol and oral calcium carbonate. Postoperative administration of intravenous calcium was given for symptoms, calcium <7.0 mg/dL, or surgeon preference. The Fisher exact test was used to compare proportions. The Wilcoxon test was used to compare continuous data. Multivariable logistic regression adjusted for confounders. RESULTS: Included were 81 patients who received subtotal parathyroidectomy for renal-origin hyperparathyroidism (41 patients who received preoperative calcitriol treatment, 40 patients who did not receive preoperative calcitriol treatment). Preoperative calcitriol treatment use increased over time (0% 2004-2010, 69% 2011-2016). Groups who received preoperative calcitriol treatment and groups who did not receive preoperative calcitriol treatment were similar in preoperative serum calcium, vitamin D, parathyroid hormone, and median age (P > .05 for all). Patients who received preoperative calcitriol treatment less often required postoperative administration of intravenous calcium (34% vs 90% of patients who did not receive preoperative calcitriol treatment, P < .001). Median length of stay was 2.0 days shorter for patients who received preoperative calcitriol treatment versus patients who did not receive preoperative calcitriol treatment patients (P < .001). Factors associated with postoperative administration of intravenous calcium included not receiving preoperative calcitriol treatment, low preoperative calcium, and high preoperative parathyroid hormone. After multivariable adjustment, preoperative calcitriol treatment remained independently associated with reduced postoperative administration of intravenous calcium (OR 0.02, P < .001). CONCLUSION: Preoperative calcitriol therapy lowered use of postoperative administration of intravenous calcium by 56% and length of stay by 50% in subtotal parathyroidectomy for renal-origin hyperparathyroidism patients. We believe preoperative calcitriol treatment should become standard of care for subtotal parathyroidectomy for renal-origin hyperparathyroidism.

Keeping primary aldosteronism in mind: Deficiencies in screening at-risk hypertensives.

BACKGROUND: Primary aldosteronism is a common but underdiagnosed cause of hypertension. Patients with this disorder have worse morbidity compared with those with essential hypertension, but with timely diagnosis and appropriate intervention these patients are potentially cured and may have reversal of target organ damage. The goal of this study was to determine if hypertensive patients considered high risk were checked for primary aldosteronism. METHODS: We reviewed electronic health records to identify patients age 18 years or older with coexisting hypertension and hypokalemia or hypertension and sleep apnea, then determined if they had been investigated with measurement of aldosterone or renin. We built regression models to identify explanatory variables for screening in these 2 high-risk groups. RESULTS: Of nearly 37,000 patients with hypertension and hypokalemia, only 2.7% were ever screened for primary aldosteronism. Most opportunities for case detection were during inpatient hospitalizations, yet in this setting, patients were less likely than clinic patients be screened. Similarly, 3.0% of hypertensive patients with sleep apnea were screened since the inclusion of this group in case detection recommendations. CONCLUSION: Uptake of practice guidelines by hospital physicians, fueled by support from their specialty societies, may help to identify many more patients with unrecognized primary aldosteronism.

Robot-Assisted Endocrine Surgery: Indications and Drawbacks.

BACKGROUND: Over the last few decades, robotic surgery with the da Vinci system has become increasingly prevalent. Endocrine surgeons are witnessing a rapid growth in enthusiasm for robotic approaches for treating thyroid, parathyroid, and adrenal disease. For carefully selected patients, the robotic system may be the preferred technique, although its use remains controversial and indications are in evolution. The goal of this article is to review current robotic procedures for thyroidectomy, parathyroidectomy, and adrenalectomy, and scrutinize the existing literature for application of these approaches. METHODS: We systematically searched and reviewed relevant articles on PubMed and MEDLINE databases for robotic or robot-assisted thyroidectomy, parathyroidectomy, or adrenalectomy. RESULTS: The safety and feasibility for robotic thyroidectomy, parathyroidectomy, and adrenalectomy have been repeatedly demonstrated. Although robotic thyroid and parathyroid surgery offers better cosmetic results compared to the conventional open operation, remote-access techniques introduce new risks. Similar outcomes have been reported for laparoscopic and robotic adrenalectomy, but robot-assisted techniques may extend the capabilities of minimally invasive surgery, particularly performing subtotal adrenalectomy. CONCLUSIONS: While robotic procedures offer better ergonomics for the endocrine surgeon and improved cosmesis for the patient, the major drawback to the robot system almost universally is the higher cost. With new robotically assisted surgical devices on the way that could drive down costs and speed up innovation, the indications for robotic endocrine surgery may greatly expand.

Large Cytologically Benign Thyroid Nodules Do Not Have High Rates of Malignancy or False-Negative Rates and Clinical Observation Should be Considered: A Meta-Analysis.

Background: Management of large thyroid nodules is controversial, as data are conflicting regarding overall rates of malignancy (ROM) in all nodules and frequency of false-negative fine-needle aspiration results (FNR) in cytologically benign nodules. This meta-analysis aimed to evaluate and compare ROM and FNR in small versus large nodules published in the literature. Methods: Articles indexed in PubMed, written in English, published electronically or in print on or prior to December 8 2017 were searched for "false negative thyroid size or cm" and "malignancy rates benign thyroid nodules." Three hundred fifty-two unique citations were identified. Multiple reviewers selected a final set of 35 articles that contained nodules stratified by size (3, 4, or 5 cm), with benign or all cytologic diagnoses, and with postsurgical histologic diagnoses. Multiple observers extracted data, including numbers of total, cytologically benign, and histologically malignant nodules. Size cutoffs of 3, 4, and/or 5 cm were analyzed in 14, 24, and 1 article, respectively. Results: ROM in all nodules ≥3 cm (13.1%) and ≥4 cm (20.9%) was lower than those <3 cm (19.6%) and <4 cm (19.9%; odds ratio [OR] = 0.72 [confidence interval (CI) 0.64-0.81] and OR = 0.85 [CI 0.77-0.95]). FNR in nodules ≥3 cm (7.2%) was not different from smaller nodules (5.7%; OR = 1.47 [CI 0.80-2.69]). FNR in nodules ≥4 cm (6.7%) was slightly higher than those <4 cm (4.5%; OR = 1.38 [CI 1.06-1.80]). The most frequently reported false-negative diagnosis was papillary thyroid carcinoma. Conclusions: Rates of malignancy and false-negative FNA results vary but, in most studies, are not higher in larger nodules. Patients with large, cytologically benign thyroid nodules need not undergo immediate surgical resection, as false-negative FNA rates are low and are expected to decrease in light of nomenclature revision of a subset of follicular variants of papillary thyroid carcinoma.

Quality of life in thyroid cancer-assessment of physician perceptions.

BACKGROUND: Thyroid cancer is the fastest growing malignancy in the United States. Previous studies have shown a decrease in quality of life (QoL) after the treatment of thyroid cancer. To date, there have been no studies assessing physician perceptions regarding how a diagnosis of thyroid cancer affects QoL. Based on this and other findings from our study, we aim to assess physician perceptions on the effect of thyroid cancer on QoL. MATERIALS AND METHODS: Physicians were recruited from two national organizations comprised physicians focusing on thyroid cancer. A 37-question survey was administered evaluating physician's perceptions of thyroid cancer patient satisfaction in various aspects of treatment, complications, and overall effects on QoL. QoL responses were categorized into overall QoL, physical, psychological, social, and spiritual well-being. RESULTS: One hundred five physicians completed the survey. Physician's estimates of patient's overall QoL after thyroid cancer treatment was similar to overall QoL reported by patients. However, medical physicians overestimated the decrease in thyroid cancer survivor's QoL in several subcategories including physical, psychological, and social (P < 0.05). Both surgeons and medical physicians underestimated the percentage of patients with reported symptoms of temporary and permanent voice changes, temporary dry mouth, cold/heat sensitivity, and temporary and permanent hypocalcemia (P = 0.01-0.04). CONCLUSIONS: Physicians have a varied estimation of the detrimental impact of thyroid cancer treatment on QoL. In addition, physicians underestimated the amount of physical symptoms associated with thyroid cancer treatments. Increased physician awareness of the detrimental effects of a thyroid cancer diagnosis on QoL should allow for a more accurate conversation about expected outcomes after thyroid cancer treatment.

An update in international trends in incidence rates of thyroid cancer, 1973-2007.

PURPOSE: Over the past several decades, there has been a reported increase in the incidence of thyroid cancer in many countries. We previously reported an increase in thyroid cancer incidence across continents between 1973 and 2002. Here, we provide an update on the international trends in thyroid cancer between 2003 and 2007. METHODS: We examined thyroid cancer incidence data from the Cancer Incidence in Five Continents (CI5) database for the period between 1973 and 2007 from 24 populations in the Americas, Asia, Europe, Africa and Oceania, and report on the time trends as well as the distribution by histologic type and gender worldwide. RESULTS: The incidence of thyroid cancer increased during the period from 1998-2002 to 2003-2007 in the majority of populations examined, with the highest rates observed among women, most notably in Israel and the United States SEER registry, at over 14 per 100,000 people. This update suggests that incidence is rising in a similar fashion across all regions of the world. The histologic and gender distributions in the updated CI5 are consistent with the previous report. CONCLUSIONS: Our analysis of the published CI5 data illustrates that the incidence of thyroid cancer increased between 1998-2002 and 2003-2007 in most populations worldwide, and rising rates continue in all regions of the world.