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Background: Cytopathological evaluation of thyroid fine-needle aspiration biopsy (FNAB) specimens can fail to raise preoperative suspicion of medullary thyroid carcinoma (MTC). The Afirma RNA-sequencing MTC classifier identifies MTC among FNA samples that are cytologically indeterminate, suspicious, or malignant (Bethesda categories III-VI). In this study we report the development and clinical performance of this MTC classifier. Methods: Algorithm training was performed with a set of 483 FNAB specimens (21 MTC and 462 non-MTC). A support vector machine classifier was developed using 108 differentially expressed genes, which includes the 5 genes in the prior Afirma microarray-based MTC cassette. Results: The final MTC classifier was blindly tested on 211 preoperative FNAB specimens with subsequent surgical pathology, including 21 MTC and 190 non-MTC specimens from benign and malignant thyroid nodules independent from those used in training. The classifier had 100% sensitivity (21/21 MTC FNAB specimens correctly called positive; 95% confidence interval [CI] = 83.9-100%) and 100% specificity (190/190 non-MTC FNAs correctly called negative; CI = 98.1-100%). All positive samples had pathological confirmation of MTC, while all negative samples were negative for MTC on surgical pathology. Conclusions: The RNA-sequencing MTC classifier accurately identified MTC from preoperative thyroid nodule FNAB specimens in an independent validation cohort. This identification may facilitate an MTC-specific preoperative evaluation and resulting treatment.

ObjectiveCancer patients and survivors may be disproportionately affected by COVID-19. We sought to determine the effects of the pandemic on thyroid cancer survivors' health care interactions and quality of life.MethodsAn anonymous survey including questions about COVID-19 and the Patient-Reported Outcomes Measurement Information System profile (PROMIS-29, version 2.0) was hosted on the Thyroid Cancer Survivors' Association, Inc website. PROMIS scores were compared to previously published data. Factors associated with greater anxiety were evaluated with univariable and multivariable logistic regression.ResultsFrom May 6, 2020, to October 8, 2020, 413 participants consented to take the survey; 378 (92%) met the inclusion criteria: diagnosed with thyroid cancer or noninvasive follicular neoplasm with papillary-like nuclear features, located within the United States, and completed all sections of the survey. The mean age was 53 years, 89% were women, and 74% had papillary thyroid cancer. Most respondents agreed/strongly agreed (83%) that their lives were very different during the COVID-19 pandemic, as were their interactions with doctors (79%). A minority (43%) were satisfied with the information from their doctor regarding COVID-19 changes. Compared to pre-COVID-19, PROMIS scores were higher for anxiety (57.8 vs 56.5; P < .05) and lower for the ability to participate in social activities (46.2 vs 48.1; P < .01), fatigue (55.8 vs 57.9; P < .01), and sleep disturbance (54.7 vs 56.1; P < .01). After adjusting for confounders, higher anxiety was associated with younger age (P < .01) and change in treatment plan (P = .04).ConclusionDuring the COVID-19 pandemic, thyroid cancer survivors reported increased anxiety compared to a pre-COVID cohort. To deliver comprehensive care, providers must better understand patient concerns and improve communication about potential changes to treatment plans.

BackgroundGuidelines recommend screening for primary aldosteronism in patients diagnosed with hypertension and obstructive sleep apnea. Recent studies have shown that adherence to these recommendations is extremely low. It has been suggested that cost is a barrier to implementation. No analysis has been done to rigorously evaluate the cost-effectiveness of widespread implementation of these guidelines.MethodsWe constructed a decision-analytic model to evaluate screening of the hypertensive obstructive sleep apnea population for primary aldosteronism as per guideline recommendations in comparison with current rates of screening. Probabilities, utility values, and costs were identified in the literature. Threshold and sensitivity analyses assessed robustness of the model. Costs were represented in 2020 US dollars and health outcomes in quality-adjusted life-years. The model assumed a societal perspective with a lifetime time horizon.ResultsScreening per guideline recommendations had an expected cost of $47,016 and 35.27 quality-adjusted life-years. Continuing at current rates of screening had an expected cost of $48,350 and 34.86 quality-adjusted life-years. Screening was dominant, as it was both less costly and more effective. These results were robust to sensitivity analysis of disease prevalence, test sensitivity, patient age, and expected outcome of medical or surgical treatment of primary aldosteronism. The screening strategy remained cost-effective even if screening were conservatively presumed to identify only 3% of new primary aldosteronism cases.ConclusionsFor patients with hypertension and obstructive sleep apnea, rigorous screening for primary aldosteronism is cost-saving due to cardiovascular risk averted. Cost should not be a barrier to improving primary aldosteronism screening adherence.

BackgroundResistant hypertension is common in patients with primary aldosteronism and in those with obstructive sleep apnea. Primary aldosteronism treatment improves sleep apnea. Despite Endocrine Society guidelines' inclusion of sleep apnea and hypertension co-diagnosis as a primary aldosteronism screening indication, the state of screening implementation is unknown.MethodsAll hypertensive adult patients with obstructive sleep apnea (n = 4751) at one institution between 2012 and 2020 were compared with a control cohort without sleep apnea (n = 117,815). We compared the association of primary aldosteronism diagnoses, risk factors, and screening between both groups. Patients were considered to have screening if they had a primary aldosteronism diagnosis or serum aldosterone or plasma renin activity evaluation.ResultsObstructive sleep apnea patients were predominantly men and had higher body mass index. On multivariable analysis, hypertensive sleep apnea patients had higher odds of drug-resistant hypertension (odds ratio [OR] 2.70; P < .001) and hypokalemia (OR 1.26; P < .001) independent of body mass index, sex, and number of antihypertensive medications. Overall, sleep apnea patients were more likely to be screened for primary aldosteronism (OR 1.45; P < .001); however, few patients underwent screening whether they had sleep apnea or not (pre-guideline publication 7.8% vs 4.6%; post-guidelines 3.6% vs 4.6%; P < .01). Screening among eligible sleep apnea patients remained low prior to and after guideline publication (4.4% vs 3.4%).ConclusionsObstructive sleep apnea is associated with primary aldosteronism risk factors without formal diagnosis, suggesting screening underutilization and underdiagnosis. Strategies are needed to increase screening adherence, as patients may benefit from treatment of concomitant primary aldosteronism to reduce sleep apnea severity and its associated cardiopulmonary morbidity.

Parathyroid allotransplantation is a burgeoning treatment for severe hypoparathyroidism. Deceased donor parathyroid gland (PTG) procurement can be technically challenging due to lack of normal intraoperative landmarks and exposure constraints in the neck of organ donors. In this study, we assessed standard 4-gland exposure in situ and en bloc surgical techniques for PTG procurement and ex vivo near-infrared autofluorescence (NIRAF) imaging for identification of PTGs during organ recovery.MethodsResearch tissue consent was obtained from organ donors or donor families for PTG procurement. All donors were normocalcemic, brain-dead, solid organ donors between 18 and 65 y of age. PTGs were procured initially using a standard 4-gland exposure technique in situ and subsequently using a novel en bloc resection technique after systemic organ preservation flushing. Parathyroid tissue was stored at 4 °C in the University of Wisconsin solution up to 48 h post-procurement. Fluoptics Fluobeam NIRAF camera and Image J software were utilized for quantification of NIRAF signal.ResultsThirty-one brain-dead deceased donor PTG procurements were performed by abdominal transplant surgeons. In the initial 8 deceased donors, a mean of 1.75 glands (±1.48 glands SD) per donor were recovered using the 4-gland in situ technique. Implementation of combined en bloc resection with ex vivo NIRAF imaging in 23 consecutive donors yielded a mean of 3.60 glands (±0.4 SD) recovered per donor (P < 0.0001). Quantification of NIRAF integrated density signal demonstrated >1-fold log difference in PTG (2.13 × 105 pixels) versus surrounding anterior neck structures (1.9 × 104 pixels; P < 0.0001). PTGs maintain distinct NIRAF signal from the time of recovery (1.88 × 105 pixels) up to 48 h post-procurement (1.55 × 105 pixels) in organ preservation cold storage (P = 0.34).ConclusionsThe use of an en bloc surgical technique with ex vivo NIRAF imaging significantly enhances the identification and recovery of PTG from deceased donors.

The purpose of this prospective study was to determine the correct localization rate (CLR) of 18F-fluorocholine PET for the detection of parathyroid adenomas in comparison to 99mTc-sestamibi imaging. Methods: This was a single-arm prospective trial. Ninety-eight patients with biochemical evidence of primary hyperparathyroidism were imaged before parathyroidectomy using 18F-fluorocholine PET/MRI. 99mTc-sestamibi imaging performed separately from the study was evaluated for comparison. The primary endpoint of the study was the CLR on a patient level. Each imaging study was interpreted by 3 masked readers on a per-region basis. Lesions were validated by histopathologic analysis of surgical specimens. Results: Of the 98 patients who underwent 18F-fluorocholine PET, 77 subsequently underwent parathyroidectomy and 60 of those had 99mTc-sestamibi imaging. For 18F-fluorocholine PET in patients who underwent parathyroidectomy, the CLR based on the masked reader consensus was 75% (95% CI, 0.63-0.82). In patients who underwent surgery and had an available 99mTc-sestamibi study, the CLR increased from 17% (95% CI, 0.10-0.27) for 99mTc-sestamibi imaging to 70% (95% CI, 0.59-0.79) for 18F-fluorocholine PET. Conclusion: In this prospective study using masked readers, the CLR for 18F-fluorocholine PET was 75%. In patients with a paired 99mTc-sestamibi study, the use of 18F-fluorocholine PET increased the CLR from 17% to 70%. 18F-fluorocholine PET is a superior imaging modality for the localization of parathyroid adenomas.

Abstract Background: The coronavirus (COVID-19) pandemic has led to rapid changes in our society and healthcare system. Cancer patients and survivors may be disproportionately affected by these changes, including decreased access to healthcare, increased infection risk, and economic challenges. We sought to determine the effects of the pandemic on thyroid cancer survivors’ quality of life. Methods: An anonymous web-based survey was administered in collaboration with ThyCa: Thyroid Cancer Survivors’ Association, consisting of questions about (1) demographics, (2) thyroid cancer clinical characteristics, (3) attitudes toward and impact of COVID-19, and (4) the Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item profile. The survey was linked on the ThyCa homepage. PROMIS measures were scored using item response theory models with a T-score metric relative to U.S. reference data via the HealthMeasures Scoring Service (https://www.healthmeasures.net). T-scores were analyzed using Mann-Whitney U, Wilcoxon signed-rank, Kruskal-Wallis, and Spearman’s rank correlation tests. Results: From 5/6/2020 - 10/8/2020, 505 participants accessed the survey, and all completed surveys by U.S.-based thyroid cancer survivors were analyzed (n=378, 75%). Mean age was 53 years, 89% were female, 90% were white, 74% had papillary thyroid cancer, 97% had surgery, and 70% received radioactive iodine. The vast majority agreed or strongly agreed (83%) that their lives were very different during COVID-19, as was the way they interacted with their doctors (79%). Less than half (43%) agreed or strongly agreed that they were satisfied with the amount of information from their doctor’s office regarding COVID-19 changes. Compared to previously-published PROMIS data for this population, T-scores were significantly higher in the domain of anxiety/fear (57.8 vs. 56.5, p

Molecular mechanisms mediating tonic secretion of parathyroid hormone (PTH) in response to hypocalcaemia and hyperparathyroidism (HPT) are unclear. Here we demonstrate increased heterocomplex formation between the calcium-sensing receptor (CaSR) and metabotropic γ-aminobutyric acid (GABA) B1 receptor (GABAB1R) in hyperplastic parathyroid glands (PTGs) of patients with primary and secondary HPT. Targeted ablation of GABAB1R or glutamic acid decarboxylase 1 and 2 in PTGs produces hypocalcaemia and hypoparathyroidism, and prevents PTH hypersecretion in PTGs cultured from mouse models of hereditary HPT and dietary calcium-deficiency. Cobinding of the CaSR/GABAB1R complex by baclofen and high extracellular calcium blocks the coupling of heterotrimeric G-proteins to homomeric CaSRs in cultured cells and promotes PTH secretion in cultured mouse PTGs. These results combined with the ability of PTG to synthesize GABA support a critical autocrine action of GABA/GABAB1R in mediating tonic PTH secretion of PTGs and ascribe aberrant activities of CaSR/GABAB1R heteromer to HPT.

ImportanceTransoral 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.ObjectiveTo determine what percentage of US patients undergoing thyroid and parathyroid surgery are eligible for TES using currently accepted exclusion criteria.Design, setting, and participantsCross-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 measuresThe 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.ResultsThe 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 relevanceMore 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.

BackgroundIdentification of Hürthle cell cancers by non-operative fine-needle aspiration biopsy (FNAB) of thyroid nodules is challenging. Resultingly, non-cancerous Hürthle lesions were conventionally distinguished from Hürthle cell cancers by histopathological examination of tissue following surgical resection. Reliance on histopathological evaluation requires patients to undergo surgery to obtain a diagnosis despite most being non-cancerous. It is highly desirable to avoid surgery and to provide accurate classification of benignity versus malignancy from FNAB preoperatively. In our first-generation algorithm, Gene Expression Classifier (GEC), we achieved this goal by using machine learning (ML) on gene expression features. The classifier is sensitive, but not specific due in part to the presence of non-neoplastic benign Hürthle cells in many FNAB.ResultsWe sought to overcome this low-specificity limitation by expanding the feature set for ML using next-generation whole transcriptome RNA sequencing and called the improved algorithm the Genomic Sequencing Classifier (GSC). The Hürthle identification leverages mitochondrial expression and we developed novel feature extraction mechanisms to measure chromosomal and genomic level loss-of-heterozygosity (LOH) for the algorithm. Additionally, we developed a multi-layered system of cascading classifiers to sequentially triage Hürthle cell-containing FNAB, including: 1. presence of Hürthle cells, 2. presence of neoplastic Hürthle cells, and 3. presence of benign Hürthle cells. The final Hürthle cell Index utilizes 1048 nuclear and mitochondrial genes; and Hürthle cell Neoplasm Index leverages LOH features as well as 2041 genes. Both indices are Support Vector Machine (SVM) based. The third classifier, the GSC Benign/Suspicious classifier, utilizes 1115 core genes and is an ensemble classifier incorporating 12 individual models.ConclusionsThe accurate algorithmic depiction of this complex biological system among Hürthle subtypes results in a dramatic improvement of classification performance; specificity among Hürthle cell neoplasms increases from 11.8% with the GEC to 58.8% with the GSC, while maintaining the same sensitivity of 89%.

BackgroundMinimally invasive and remote access thyroid surgery has been evolving with the transoral endoscopic thyroidectomy vestibular approach (TOETVA) emerging as a true "scarless" thyroidectomy. In this study, we describe a hybrid transoral and submental thyroidectomy (TOaST) technique for thyroid lobectomy.Materials and methodsA TOaST right thyroid lobectomy was performed for a 4 cm cytologically benign right thyroid nodule. Initial incision was made in the submental region with two additional 5 mm lateral ports inserted transorally. Right thyroid lobectomy proceeded via standard TOETVA with intact specimen extraction via the submental incision.ResultsThe patient was discharged home on postoperative day 1. Final pathology showed a 4.2 cm follicular adenoma. Cosmetic results and patient satisfaction were excellent.DiscussionThis is the first reported case of a hybrid TOaST technique. It aims to maintain the principles and advantages of TOETVA while addressing its limitations related to large tumor extraction, mental nerve injury, and chin sensory changes. The shorter distance of dissection required may reduce postoperative pain. This approach may expand the indications for transoral thyroidectomy while maintaining excellent cosmetic outcomes.

ImportanceLaparoscopic adrenalectomy is the gold standard for most adrenal disorders and its frequency in the United States is increasing. While national and administrative databases can adjust for patient factors, comorbidities, and institutional variations, granular disease-specific data that may significantly influence the incidence of perioperative complications and length of stay (LOS) are lacking.ObjectiveTo investigate factors associated with perioperative complications and LOS after laparoscopic adrenalectomy.Design, setting, and participantsThis cohort study was carried out at a single academic medical center, with all patients who underwent laparoscopic adrenalectomy between 1993 and 2017 by the endocrine surgery department. Multivariable linear and logistic regression were used to obtain adjusted odds ratios (ORs).Main outcomes and measuresThe primary outcome was perioperative complications with a Dindo-Clavien grade of 2 or more. The secondary outcome was prolonged length of stay, defined as a stay longer than the 75th percentile of the overall cohort.ResultsWe identified 640 patients who underwent 653 laparoscopic adrenalectomies, of whom 370 (56.7%) were female. The median age was 51 (range, 5-88) years. A total of 76 complications with a Dindo-Clavien grade of 2 or more occurred in 55 patients (8.4%), with postoperative mortality in 2 patients (0.3%). The median hospital length of stay was 1 day (range, 0-32 days). Factors independently associated with increased complications were American Society of Anesthesiologists class 3 or 4 (OR, 2.78 [95% CI, 1.39-5.55]; P

BackgroundPrimary hyperparathyroidism (PHPT) is a common endocrine disorder that predominantly affects patients >60 and is increasing in prevalence. Identifying risk factors for poor outcomes after parathyroidectomy in older adults will help tailor operative decision making. The impact of frailty on surgical outcomes in parathyroidectomy has not been established.MethodsWe performed a retrospective review of patients ≥40 years who underwent parathyroidectomy in the 2005-2010 ACS NSQIP. Frailty was assessed using the modified frailty index (mFI). Multivariable regression was used to determine the association of frailty with 30-day complications, length of stay (LOS), and reoperation.ResultsWe identified 13,123 patients ≥40 who underwent parathyroidectomy for PHPT. The majority of patients were not frail, with 80% with a low NSQIP mFI score (0-1 frailty traits), 19% with an intermediate mFI score (2-3), and 0.9% with a high mFI score (≥4). Overall 30-day complications were rare, occurring in 141 (1.1%) patients. Increasing frailty was associated with an increased risk of complications with adjusted odds ratios (ORs) of 1.76 (95% CI 1.20-2.59; p = 0.004) for intermediate and 8.43 (95% CI 4.33-16.41; p

The newly introduced pathologic diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) will result in less bilateral thyroid surgery as well as deescalation in T4 suppressive and radioactive iodine treatment. Although, NIFTP is a nonmalignant lesion that has nuclear features of some papillary malignancies, the challenge for the surgeon is to identify a lesion as possibly NIFTP before the pathologic diagnosis. NIFTP, due to its reduction of overall rates of malignancy, will result in the initial surgical pendulum swinging toward lobectomy instead of initial total thyroidectomy. This American Head and Neck Society endocrine section consensus statement is intended to inform preoperative evaluation to attempt to identify those patients whose final pathology report may ultimately harbor NIFTP and can be offered a conservative surgical plan to assist in cost-effective, optimal management of patients with NIFTP.

ImportanceUse of next-generation sequencing of RNA and machine learning algorithms can classify the risk of malignancy in cytologically indeterminate thyroid nodules to limit unnecessary diagnostic surgery.ObjectiveTo measure the performance of a genomic sequencing classifier for cytologically indeterminate thyroid nodules.Design, setting, and participantsA blinded validation study was conducted on a set of cytologically indeterminate thyroid nodules collected by fine-needle aspiration biopsy between June 2009 and December 2010 from 49 academic and community centers in the United States. All patients underwent surgery without genomic information and were assigned a histopathology diagnosis by an expert panel blinded to all genomic information. There were 210 potentially eligible thyroid biopsy samples with Bethesda III or IV indeterminate cytopathology that constituted a cohort previously used to validate the gene expression classifier. Of these, 191 samples (91.0%) had adequate residual RNA for validation of the genomic sequencing classifier. Algorithm development and independent validation occurred between August 2016 and May 2017.ExposuresThyroid nodule surgical histopathology diagnosis by an expert panel blinded to all genomic data.Main outcomes and measuresThe primary end point was measurement of genomic sequencing classifier sensitivity, specificity, and negative and positive predictive values in biopsies from Bethesda III and IV nodules. The secondary end point was measurement of classifier performance in biopsies from Bethesda II, V, and VI nodules.ResultsOf the 183 included patients, 142 (77.6%) were women, and the mean (range) age was 51.7 (22.0-85.0) years. The genomic sequencing classifier had a sensitivity of 91% (95% CI, 79-98) and a specificity of 68% (95% CI, 60-76). At 24% cancer prevalence, the negative predictive value was 96% (95% CI, 90-99) and the positive predictive value was 47% (95% CI, 36-58).Conclusions and relevanceThe genomic sequencing classifier demonstrates high sensitivity and accuracy for identifying benign nodules. Its 36% increase in specificity compared with the gene expression classifier potentially increases the number of patients with benign nodules who can safely avoid unnecessary diagnostic surgery.

Genetic testing for pheochromocytoma and paraganglioma allows for early detection of hereditary syndromes and enables close follow-up of high-risk patient. We investigated the trends in genetic testing among patients at a high-volume referral center and evaluated the prevalence of pheochromocytomas and paragangliomas.We reviewed the charts of 129 patients who underwent adrenalectomy for pheochromocytoma and paraganglioma between January 2000 and July 2015. To evaluate for trends in genetic testing, patients were divided by year of diagnosis: 2000-2005 (group 1, n = 35), 2006-2010 (group 2, n = 44), and 2011-2015 (group 3, n = 50).Among 129 patients the mean age was 47 years and 56% were women. Groups 2 and 3 were more frequently referred for genetic consultation than group 1, 73%, and 94% versus 26% (P

BACKGROUND:Papillary thyroid carcinoma with squamous differentiation (PTC-SD) is a poorly understood pathologic finding of unknown clinical significance. Selected case reports have suggested that PTC-SD is an aggressive tumor with a poor prognosis. Here we present the largest case series of PTC-SD reported in the United States. MATERIALS AND METHODS:The cancer registry at our tertiary care referral center was reviewed to identify all patients from 1995-2015 who had been diagnosed with PTC-SD on initial total thyroidectomy or lymph node dissection for recurrent disease. All cases were reviewed by an endocrine pathologist to confirm the diagnosis. Patient demographic, pathology, and outcomes data were collected and reviewed. RESULTS:During the study period, ten patients were diagnosed with PTC-SD, six in the primary tumor at the time of initial surgery, and four in lymph node metastases during surgery for recurrent disease. The median age at diagnosis was 56 y and half of the patients were male. Aggressive features such as multifocality (67%), extrathyroidal extension (67%), positive margin (89%), lymph node metastases (80%), and extranodal extension (60%) were far more prominent than is typically seen in classic PTC. Long-term follow-up (median 56.5 mo) demonstrated high rates of locoregional recurrence (60%), pulmonary metastases (30%), and mortality (10%). CONCLUSIONS:Squamous differentiation is a rare finding in PTC that is associated with aggressive pathologic features and poor long-term outcomes. This phenomenon may represent a step in progression toward dedifferentiation; thus, patients with PTC-SD should have close, life-long surveillance and should be treated according to evidence-based guidelines for high-risk thyroid cancers.

ImportanceFrailty is a measure of decreased physiological reserve that is associated with morbidity and mortality in major elective and emergency general surgery operations, independent of chronological age. To date, the association of frailty with outcomes in ambulatory general surgery has not been established.ObjectiveTo determine the association between frailty and perioperative morbidity in patients undergoing ambulatory general surgery operations.Design, setting, and participantsA retrospective cohort study was conducted of 140 828 patients older than 40 years of age from the 2007-2010 American College of Surgeons National Surgical Quality Improvement Program Participant Use File who underwent ambulatory and 23-hour-stay hernia, breast, thyroid, or parathyroid surgery. Data analysis was performed from August 18, 2016, to June 21, 2017.Main outcomes and measuresThe association between the National Surgical Quality Improvement Program modified frailty index and perioperative morbidity was determined via multivariable logistic regression with random-effects modeling to control for clustering within Current Procedural Terminology codes.ResultsA total of 140 828 patients (80 147 women and 60 681 men; mean [SD] age, 59.3 [12.0] years) underwent ambulatory hernia (n = 71 455), breast (n = 51 267), thyroid, or parathyroid surgery (n = 18 106). Of these patients, 2457 (1.7%) experienced any type of perioperative complication and 971 (0.7%) experienced serious perioperative complications. An increasing modified frailty index was associated with a stepwise increase in the incidence of complications. In multivariable analysis adjusting for age, sex, race/ethnicity, anesthesia type, tobacco use, renal failure, corticosteroid use, and clustering by Current Procedural Terminology codes, an intermediate modified frailty index score (0.18-0.35, corresponding to 2-3 frailty traits) was associated with statistically significant odds ratios of 1.70 (95% CI, 1.54-1.88; P

BACKGROUND:The 7th AJCC T-stage system for adrenocortical carcinoma (ACC), based on size and extra-adrenal invasion, does not adequately stratify patients by survival. Lymphovascular invasion (LVI) is a known poor prognostic factor. We propose a novel T-stage system that incorporates LVI to better risk-stratify patients undergoing resection for ACC. METHOD:Patients undergoing curative-intent resections for ACC from 1993 to 2014 at 13 institutions comprising the US ACC Group were included. Primary outcome was disease-specific survival (DSS). RESULTS:Of the 265 patients with ACC, 149 were included for analysis. The current T-stage system failed to differentiate patients with T2 versus T3 disease (p = 0.10). Presence of LVI was associated with worse DSS versus no LVI (36 mo vs. 168 mo; p = 0.001). After accounting for the individual components of the current T-stage system (size, extra-adrenal invasion), LVI remained a poor prognostic factor on multivariable analysis (hazard ratio 2.14, 95% confidence interval 1.05-4.38, p = 0.04). LVI positivity further stratified patients with T2 and T3 disease (T2: 37 mo vs. median not reached; T3: 36 mo vs. 96 mo; p = 0.03) but did not influence survival in patients with T1 or T4 disease. By incorporating LVI, a new T-stage classification system was created: [T1: ≤ 5 cm, (-)local invasion, (+/-)LVI; T2: > 5 cm, (-)local invasion, (-)LVI OR any size, (+)local invasion, (-)LVI; T3: > 5 cm, (-)local invasion, (+)LVI OR any size, (+)local invasion, (+)LVI; T4: any size, (+)adjacent organ invasion, (+/-)LVI]. Each progressive new T-stage group was associated with worse median DSS (T1: 167 mo; T2: 96 mo; T3: 37 mo; T4: 15 mo; p

Hypoparathyroidism is a potential outcome of anterior neck surgery. Commonly it is managed by calcium and vitamin D supplementation in large doses, with attendant side effects. A recombinant human parathyroid hormone (rhPTH) is now available in the USA, offering a potentially more effective treatment. No cost-effectiveness model investigating this new medication versus standard care has yet been published.We constructed a decision analytic model comparing usual care versus rhPTH treatment for postsurgical hypoparathyroidism. Threshold and sensitivity analyses on key parameters were conducted to assess robustness of the model. Costs and health outcomes were represented in US dollars and quality-adjusted life-years (QALYs).The rhPTH strategy was both more costly and more effective than the usual care (UC) strategy. In the base case, UC cost $37,196 and provided 7.54 QALYs. The rhPTH strategy cost $777,224 and provided 8.46 QALYs for an incremental cost-effectiveness ratio of $804,378/QALY. As this was above our willingness-to-pay of $100,000, treatment with rhPTH was not considered cost-effective. The model was robust to all other parameters.To our knowledge, this is the first formal cost-effectiveness analysis of rhPTH in comparison with UC. Our model suggests that although the new treatment is slightly more effective than UC, the modest gain in quality of life for patients who are reasonably well-managed by UC does not justify the cost. However, consideration must be given to rhPTH for patients who have failed UC, as the expenditure may be justified in that context.

BackgroundGuidelines for management of small adrenal incidentalomas are mutually inconsistent. No cost-effectiveness analysis has been performed to evaluate rigorously the relative merits of these strategies.MethodsWe constructed a decision-analytic model to evaluate surveillance strategies for

Background and objectivesPathological examination occasionally reveals incidental central lymph nodes metastasis (iLNM) after thyroidectomy for patients with papillary thyroid cancer (PTC) who did not undergo compartment-orientated lymphadenectomy. We aimed to investigate the risk of recurrence for patients with iLNM.MethodsWe conducted a retrospective review of all patients undergoing total thyroidectomy for PTC (January 2000 to January 2010). Patients with distant metastases, central- or lateral neck dissection and pre-operative suspicious lymph nodes (by ultrasound or clinical examination) were excluded. The association between iLNM and recurrent disease was investigated using Kaplan-Meier survival estimates and Cox proportional hazards analysis.Results225/1000 patients had incidental nodes after total thyroidectomy for PTC. 183 were node-negative and 42 had iLNM. Mean age was 46 years and 201 (89%) were women. Mean number of resected nodes was 2.3. Disease recurred in 8/183 (4.4%) of patients with N0 versus 7/42 (17%) with iLNM. After adjusting for other factors, iLNM was independently associated with recurrent disease (hazard ratio = 4.01 [95% CI 1.21-13.3]).ConclusionsPositive incidental lymph nodes are independently associated with recurrent disease in patients with PTC. These patients should therefore be monitored more carefully.

Purpose To investigate the performance of flourine 18 (18F) fluorocholine (FCH) positron emission tomography (PET)/magnetic resonance (MR) imaging in patients with hyperparathyroidism and nonlocalized disease who have negative or inconclusive results at ultrasonography (US) and technetium 99m (99mTc) sestamibi scintigraphy. Materials and Methods This study was approved by the institutional review board. Between May and December 2015, 10 patients (mean age, 70.4 years; range, 58-82 years) with biochemical primary hyperparathyroidism and inconclusive results at US and 99mTc sestamibi scintigraphy were prospectively enrolled. All patients gave informed consent. Directly after administration of 3 MBq/kg of FCH, PET imaging was performed, followed by T1- and T2-weighted MR imaging before and after gadolinium enhancement. Intraoperative localization and histologic results were the reference standard for calculating sensitivity and positive predictive value. The Wilcoxon rank test was used to calculate the mean difference in maximum standardized uptake value (SUVmax) between abnormal parathyroid uptake and physiologic thyroid uptake. The Wilcoxon rank-sum test was performed. Results MR imaging alone showed true-positive lesions in five patients and a false-positive lesion in one patient. FCH PET/MR imaging allowed correct localization of nine of 10 adenomas (90% sensitivity), without any false-positive results (100% positive predictive value). One patient had four-gland hyperplasia, of which three hyperplastic glands were not localized. The median SUVmax of the nine preoperatively identified adenomas was 4.9 (interquartile range, 2.45-7.35), which was significantly higher than the SUV, 2.7 (interquartile range, 1.6-3.8), of the thyroid (P = .008). Conclusion FCH PET/MR imaging allowed localization of adenomas with high accuracy when conventional imaging results were inconclusive and provided detailed anatomic information. More patients must be examined to confirm our initial results, and the accuracy of FCH PET/MR imaging for localization of glands in patients with four-gland hyperplasia remains to be investigated. © RSNA, 2017.

Perioperative blood transfusion is associated with decreased survival in pancreatic, gastric, and liver cancer. The effect of transfusion in adrenocortical carcinoma (ACC) has not been studied. Patients with available transfusion data undergoing curative-intent resection of ACC from 1993 to 2014 at 13 institutions comprising the United States Adrenocortical Carcinoma Group were included. Factors associated with blood transfusion were determined. Primary and secondary end points were recurrence-free survival (RFS) and overall survival (OS), respectively. Out of 265 patients, 149 were included for analysis. Out of these, 57 patients (38.3%) received perioperative transfusions. Compared to nontransfused patients, transfused patients more commonly had stage 4 disease (46% vs 24%, P = 0.01), larger tumors (15.8 vs 10.2 cm, P < 0.001), inferior vena cava involvement (24.6% vs 5.4%, P = 0.002), additional organ resection (78.9% vs 36.3%, P < 0.001), and major complications (29% vs 2%, P < 0.001). Transfusion was associated with decreased RFS (8.9 vs 24.7 months, P = 0.006) and OS (22.8 vs 91.0 months, P < 0.001). On univariate Cox regression, transfusion, stage IV, hormonal hypersecretion, and adjuvant therapy were associated with decreased RFS. On multivariable analysis, only transfusion [hazard ratio (HR) = 1.7, 95% confidence interval (CI) =1.0-2.9, P = 0.04], stage IV (HR = 3.2, 95% CI = 1.7-5.9, P < 0.001), and hormonal hypersecretion (HR = 2.6, 95% CI = 1.5-4.2, P < 0.001) were associated with worse RFS. When applying this model to OS, similar associations were seen (transfusion HR = 2.0, 95% CI = 1.1-3.8, P = 0.02; stage 4 HR = 6.2, 95% CI = 3.1-12.4, P < 0.001; hormonal hypersecretion HR = 3.5, 95% CI = 1.9-6.4, P < 0.001). There was no difference in outcomes between patients who received 1 to 2 units versus >2 units of packed red blood cells in median RFS (8.9 vs 8.4 months, P = 0.95) or OS (26.5 vs 18.6 months, P = 0.63). Perioperative transfusion is associated with earlier recurrence and decreased survival after curative-intent resection of ACC. Strategies and protocols to minimize blood transfusion should be developed and followed.

BackgroundCatecholamine excess in patients with pheochromocytoma often results in impaired glucose tolerance, leading to diabetes mellitus. Little data are available on the long-term effect of surgery on diabetes.ObjectiveThe primary aim of this study was to determine the likelihood of diabetes cure after surgery, while secondary objectives were to determine risk factors for development of diabetes preoperatively and persistence of diabetes postoperatively.MethodsAll patients undergoing surgery for pheochromocytoma from 1996 to 2015 were retrospectively reviewed to identify those with a preoperative diagnosis of diabetes. Demographic and diabetes-specific data were collected. Median follow-up was 52.1 months.ResultsOverall, 153 patients underwent surgery. Diabetes was seen in 36 (23.4%) patients. Eight patients met the exclusion criteria and were removed from the final analysis, while 22 (78.6%) patients had complete resolution of diabetes. Four patients remained on medication with improved control. Overall, 93.0% of patients had improvement of their diabetes; two patients did not improve. Patients with large, symptomatic tumors were more likely to develop preoperative diabetes, and diabetes was more likely to persist in patients who had an elevated body mass index (BMI).ConclusionsDiabetes was found concurrently with pheochromocytoma in 23% of patients, more often in those with large, symptomatic tumors. The majority of patients had long-term resolution of diabetes after successful resection; however, some patients may continue to require treatment of diabetes after operation, especially those with a higher BMI.