Making Choices: A Multi-institutional, Longitudinal Cohort Study Assessing Changes in Treatment Outcome Valuation for Low-Risk Thyroid Cancer.

OBJECTIVE: To evaluate the relative importance of treatment outcomes to patients with low-risk thyroid cancer (TC). SUMMARY BACKGROUND DATA: Overuse of total thyroidectomy (TT) for low-risk TC is common. Emotions from a cancer diagnosis may lead patients to choose TT resulting in outcomes that do not align with their preferences. METHODS: Adults with clinically low-risk TC enrolled in a prospective, multi-institutional, longitudinal cohort study from 11/2019-6/2021. Participants rated treatment outcomes at the time of their surgical decision and again 9 months later by allocating 100 points amongst 10 outcomes. T-tests and Hotelling's T 2 statistic compared outcome valuation within and between subjects based on chosen extent of surgery (TT vs. lobectomy). RESULTS: Of 177 eligible patients, 125 participated (70.6% response) and 114 completed the 9-month follow-up (91.2% retention). At the time of the treatment decision, patients choosing TT valued the risk of recurrence more than those choosing lobectomy and the need to take thyroid hormone less ( P <0.05). At repeat valuation, all patients assigned fewer points to cancer being removed and the impact of treatment on their voice, and more points to energy levels ( P <0.05). The importance of the risk of recurrence increased for those who chose lobectomy and decreased for those choosing TT ( P <0.05). CONCLUSION: The relative importance of treatment outcomes changes for patients with low-risk TC once the outcome has been experienced to favor quality of life over emotion-related outcomes. Surgeons can use this information to discuss the potential for asthenia or changes in energy levels associated with total thyroidectomy.

Routine use of intraoperative nerve monitoring is associated with a reduced risk of vocal cord dysfunction after thyroid cancer surgery.

BACKGROUND: The aim of this study was to investigate the associations between individual surgeon's intraoperative nerve monitoring (IONM) practice and factors associated with vocal cord (VC) dysfunction in patients with thyroid cancer undergoing thyroidectomy. METHODS: Using Collaborative Endocrine Surgery Quality Improvement Program (CESQIP) 2014-21 data, multivariable logistic regression analyses investigated variables associated with short- and long-term VC-dysfunction, associations of routine use of IONM with postoperative outcomes, and patient characteristics associated with IONM use. RESULTS: Among 5,446 patients (76.7% female, mean age 49 years), 68.5% had surgery by surgeons using IONM in ≥ 90% of cases (63% of surgeons, n = 73). Post-operative VC-dysfunction was diagnosed by laryngoscopy in 3.0% of patients in the short-term and 2.7% in the long-term. When surgeons routinely used IONM, the incidence of VC-dysfunction was 2.4% in the short-term and 2.2% in the long-term, compared to 4.4% and 3.7%, respectively, when surgeons did not routinely use IONM (p < 0.01). After adjustment, routine use of IONM was independently associated with reduced risk of short- (OR 0.48, p < 0.01) and long-term (OR 0.52, p < 0.01) VC-dysfunction, a lower risk of postoperative hypoparathyroidism in the short- (OR 0.67, p < 0.01) and long-term (OR 0.54, p < 0.01), and higher likelihood of same-day discharge (OR 2.03, p < 0.01). Extrathyroidal tumor extension and N1-stage were factors associated with postoperative VC-dysfunction in the short- (OR 3.12, p < 0.01; OR 1.92, p = 0.01, respectively) and long-term (OR 3.11, p < 0.01; OR 2.32, p < 0.01, respectively). CONCLUSION: Routine use of IONM was independently associated with a lower risk of endocrine surgery-specific complications and greater likelihood of same-day discharge.

Evidence-based Guidelines on the Use of Virtual Surgical Education Pertaining to the Domains of Cognition and Curriculum, Psychomotor Skills Training, and Faculty Development and Mentorship.

OBJECTIVE: To identify, categorize, and evaluate the quality of literature, and to provide evidence-based guidelines on virtual surgical education within the cognitive and curricula, psychomotor, and faculty development and mentorship domains. SUMMARY OF BACKGROUND DATA: During the coronavirus disease 2019 pandemic, utilizing virtual learning modalities is expanding rapidly. Although the innovative methods must be considered to bridge the surgical education gap, a framework is needed to avoid expansion of virtual education without proper supporting evidence in some areas. METHODS: The Association for Surgical Education formed an ad-hoc research group to evaluate the quality and methodology of the current literature on virtual education and to build evidence-based guidelines by utilizing the SiGN methodology. We identified patient/problem-intervention-comparison-outcome-style questions, conducted systematic literature reviews using PubMed, EMBASE, and Education Resources information Center databases. Then we formulated evidence-based recommendations, assessed the quality of evidence using Grading of Recommendations, Assessment, Development, and Evaluation, Newcastle-Ottawa Scale for Education, and Kirkpatrick ratings, and conducted Delphi consensus to validate the recommendations. RESULTS: Eleven patient/problem-intervention-comparison-outcome-style questions were designed by the expert committees. After screening 4723 articles by the review committee, 241 articles met inclusion criteria for full article reviews, and 166 studies were included and categorized into 3 domains: cognition and curricula (n = 92), psychomotor, (n = 119), and faculty development and mentorship (n = 119). Sixteen evidence-based recommendations were formulated and validated by an external expert panel. CONCLUSION: The evidence-based guidelines developed using SiGN methodology, provide a set of recommendations for surgical training societies, training programs, and educators on utilizing virtual surgical education and highlights the area of needs for further investigation.

Anxiety During the COVID-19 Pandemic: A Web-Based Survey of Thyroid Cancer Survivors.

OBJECTIVE: Cancer 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. METHODS: An 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. RESULTS: From 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). CONCLUSION: During 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.

Severe Hypocalcemia After Thyroidectomy: An Analysis of 7366 Patients.

OBJECTIVE: The aim of the study was to determine severe hypocalcemia rate following thyroidectomy and factors associated with its occurrence. BACKGROUND: Hypocalcemia is the most common complication after thyroidectomy. Severe post-thyroidectomy hypocalcemia can be life-threatening; data on this specific complication are scarce. METHODS: Patients who underwent thyroidectomy in the American College of Surgeons-National Surgical Quality Improvement Program thyroidectomy-targeted database (2016-2017) were abstracted. A severe hypocalcemic event was defined as hypocalcemia requiring intravenous calcium, emergent clinic/hospital visit, or a readmission for hypocalcemia. Multivariable regression was used to identify factors independently associated with occurrence of severe hypocalcemia. RESULTS: Severe hypocalcemia occurred in 5.8% (n = 428) of 7366 thyroidectomy patients, with 83.2% necessitating intravenous calcium treatment. Rate of severe hypocalcemia varied by diagnosis and procedure (0.5% for subtotal thyroidectomy to 12.5% for thyroidectomy involving neck dissections). Overall, 38.3% of severe hypocalcemic events occurred after discharge; in this subset, 59.1% experienced severe hypocalcemia despite being discharged with calcium and vitamin D. Severe hypocalcemia patients had higher rates of recurrent laryngeal nerve injury (13.4% vs 6.6%), unplanned reoperations (4.4% vs 1.3%), and longer hospital stay (30.4% vs 6.2% ≥3 days (all P < 0.01). After multivariate adjustment, severe hypocalcemia was associated with multiple factors including Graves disease [odds ratio (OR) = 2.06], lateral neck dissections (OR: 3.10), and unexpected reoperations (OR = 3.55); all P values less than 0.01. CONCLUSIONS: Severe hypocalcemia and suboptimal hypocalcemia management after thyroidectomy are common. Patients who experienced severe hypocalcemia had higher rates of nerve injury and unexpected reoperations, indicating surgical complexity and provider inexperience. More biochemical surveillance particularly a parathyroid hormone-based protocol, fine-tuned supplementation, and selective referral could reduce occurrence of this morbid complication.

Patient Perceptions on Barriers and Facilitators to Accessing Low-acuity Surgery During COVID-19 Pandemic.

BACKGROUND: The onset of the COVID-19 pandemic led to the postponement of low-acuity surgical procedures in an effort to conserve resources and ensure patient safety. This study aimed to characterize patient-reported concerns about undergoing surgical procedures during the pandemic. METHODS: We administered a cross-sectional survey to patients who had their general and plastic surgical procedures postponed at the onset of the pandemic, asking about barriers to accessing surgical care. Questions addressed dependent care, transportation, employment and insurance status, as well as perceptions of and concerns about COVID-19. Mixed methods and inductive thematic analyses were conducted. RESULTS: One hundred thirty-five patients were interviewed. We identified the following patient concerns: contracting COVID-19 in the hospital (46%), being alone during hospitalization (40%), facing financial stressors (29%), organizing transportation (28%), experiencing changes to health insurance coverage (25%), and arranging care for dependents (18%). Nonwhite participants were 5 and 2.5 times more likely to have concerns about childcare and transportation, respectively. Perceptions of decreased hospital safety and the consequences of possible COVID-19 infection led to delay in rescheduling. Education about safety measures and communication about scheduling partially mitigated concerns about COVID-19. However, uncertainty about timeline for rescheduling and resolution of the pandemic contributed to ongoing concerns. CONCLUSIONS: Providing effective surgical care during this unprecedented time requires both awareness of societal shifts impacting surgical patients and system-level change to address new barriers to care. Eliciting patients' perspectives, adapting processes to address potential barriers, and effectively educating patients about institutional measures to minimize in-hospital transmission of COVID-19 should be integrated into surgical care.

Accuracy of the Lymph Node Yield in Surgery for Papillary Thyroid Cancer in Children.

INTRODUCTION: Our aim was to determine the accuracy of lymph node yield (LNY) for pediatric patients undergoing thyroidectomy with concurrent lymph nodes harvest for clinically node-negative (cN0) papillary thyroid cancer (PTC). METHODS: Patients aged ≤ 18 years with cN0 PTC undergoing thyroidectomy were reviewed in the NCDB, 1998-2016. Demographic and clinical characteristics of patients with ≥ 1 LNY were compared to those without. A truncated beta-binomial distribution estimated the number of lymph nodes needed to detect pathologic nodal positivity, and LNY was calibrated for 90% sensitivity in nodal staging and stratified across clinical tumor size staging (T). RESULTS: 1,948 children with cN0 PTC underwent surgical resection; median age was 17 years; 83.2% were female; 47.6% were T1, 25.3% T2, 9.3% T3. 1,272 (65.3%) of these patients had lymph nodes resected, or ≥ 1 LNY. The median LNY was 5 nodes (interquartile range 2-12); 45.9% of patients had ≥ 1 metastatic lymph nodes. In the overall ≥ 1 LNY cohort, 12 nodes (CI 9-19) were needed to predict nodal positivity with > 90% sensitivity. Based on clinical T-stage, detecting a metastatic lymph node with > 90% sensitivity required a LNY of 14 for T1; 8 for T2; 6 for T3. CONCLUSION: This is the first study estimating the necessary LNY for determining nodal positivity in children with cN0 PTC. The high LNY required in small T1 tumors is likely infeasible and should not be pursued. Accuracy increases with lower LNYs for higher T-stages. Our findings can help guide prognosis and treatment for pediatric patients with PTC.

Adequacy of Lymph Node Yield for Papillary Thyroid Cancer: An Analysis of 23,131 Patients.

BACKGROUND: Threshold numbers for defining adequacy of lymph node (LN) yield have been determined for evaluation of occult nodal disease during papillary thyroid cancer (PTC) surgery. This study assesses the prevalence of adequate LN yield and estimates its association with patient clinicopathologic characteristics. MATERIALS AND METHODS: Adult patients with cN1 pT1b or pT2 and cN0 or cN1 pT3 M0 PTC ≥1 cm who received surgery with ≥1 LN resected were identified from the National Cancer Database, 2004-2015. Adequate yield was defined as removing ≥6, 9, and 18 LNs for pT1b, pT2, and pT3 stages, respectively, based on recently published literature. Univariable and multivariable logistic regression were used to determine factors associated with adequate yield. RESULTS: A total of 23,131 patients were included; 7544 (32.6%) had adequate LN yield. Rate of adequate yield increased from 19.9% to 36.6% over time. After adjustment, patients at academic facilities were more likely to have adequate yield than those at community centers [OR 1.94 (95% CI 1.55-2.41), P < 0.001]. Patients with more advanced tumors were less likely to have adequate yield (pT1b: 75.9% versus pT2: 64.5% versus pT3: 24.6% adequate LN yield, P < 0.001). Patients with adequate LN yield were 0.89 times likely to receive radioactive iodine compared with those with inadequate yield [OR 0.98 (95% CI 0.81-0.98), P = 0.02]. CONCLUSIONS: The rate of adequate LN yield has increased over time, but only a minority of lymphadenectomies performed for PTC can be defined as adequate. Disparities still exist based on patient and facility characteristics; patients with more advanced tumors appear less likely to have adequate LN yield.

Low-Risk Thyroid Cancer in Elderly: Total Thyroidectomy/RAI Predominates but Lacks Survival Advantage.

BACKGROUND: Papillary thyroid cancer (PTC) is the fastest increasing cancer in the United States; incidence increases with age. It generally has a favorable prognosis but may behave more aggressively in older patients. This study aims to describe national treatment patterns for low-risk PTC in older adults. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results-Medicare database was used to identify patients ≥66 y treated for clinical T1N0M0 PTC between 1996 and 2011. Multivariable logistic regression was used to identify factors associated with extent of surgery (total thyroidectomy versus lobectomy) and radioactive iodine (RAI) administration. Cox proportional hazards modeling was used to estimate the effect of treatment type on disease-specific survival (DSS). RESULTS: Three thousand two hundred and fourteen patients met inclusion criteria; 77.6% were women, median age was 72 y, and mean tumor size was 0.7 cm. 42.7% had preoperatively diagnosed PTC (versus incidental). 65.4% underwent total thyroidectomy, 29.0% lobectomy, and 5.6% lobectomy followed by completion thyroidectomy; 33.4% received postoperative RAI. Five- and 10-year DSS were 98.9% and 98.3%, respectively. After adjustment, larger tumor size (1.1-2 cm), multifocality, and a preoperative PTC diagnosis were associated with greater odds of undergoing more extensive surgery and receiving RAI (P < 0.0001). DSS was not associated with extent of surgery or RAI administration (P > 0.05). CONCLUSIONS: Most older adults with PTC underwent total thyroidectomy and a third received RAI; neither treatment improved DSS. In the growing elderly population, less extensive interventions for PTC may reduce morbidity and improve quality of life while preserving an excellent prognosis.

A DIRECT COMPARISON OF THE ATA AND TI-RADS ULTRASOUND SCORING SYSTEMS.

Objective: This study compares the American Thyroid Association (ATA) classification system with the 2017 American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) for predicting cancer risk in thyroid nodules. Methods: This is a retrospective review of ultrasound imaging of all adult patients with thyroid nodules >5 mm who underwent thyroidectomy at a tertiary care hospital in 2016. We assessed the ability of either system to predict malignancy based on surgical histopathology. Sensitivity, specificity, negative predictive values (NPV) and positive predictive values (PPV), and area-under-the-curve (AUC) were calculated and compared using McNemar's, Fisher exact, or DeLong's tests. Results: Three hundred and twenty-three nodules from 213 adults were included. Median patient age was 55 years; 75.6% were female. 27.2% nodules were malignant. Both ATA and ACR TI-RADS provide effective diagnostic performance, a sensitivity of 77.3% versus 78.4%, respectively, a specificity of 76.6% versus 73.2%, respectively, a PPV of 55.3% versus 52.3%, respectively, and a NPV of 90% for both. The level of agreement between the two classification systems was almost perfect (weighted Kappa statistic = 0.93, AUC 0.77 ATA versus 0.76 TI-RADS [P = .18]). However, of the 40 (TI-RADS level 3) TR3 nodules (<2.5 cm), 10% were malignant, and of the 31 (TI-RADS level 4) TR4 nodules (<1.5 cm), 38% were malignant. Conclusion: The ATA and TI-RADS classification systems appear to have similar diagnostic value for predicting thyroid cancer. However, subanalysis of TR3 and TR4 nodules with consideration of size criteria showed that there is a higher risk of missing a malignancy if the ACR TI-RADS recommendation is followed. These results should be validated in a different patient cohort with a lower incidence of cancer. Abbreviations: ACR = American College of Radiology; ATA = American Thyroid Association; FNA = Fine Needle Aspiration; κ = weighted Kappa statistic; NPV = negative predictive values; PPV = positive predictive values; TI-RADS = Thyroid Imaging Reporting and Data System; TR1 = TI-RADS level 1; TR2 = TI-RADS level 2; TR3 = TI-RADS level 3; TR4 = TI-RADS level 4; TR5 = TI-RADS level 5.

USING THE ATA AND ACR TI-RADS SONOGRAPHIC CLASSIFICATIONS AS ADJUNCTIVE PREDICTORS OF MALIGNANCY FOR INDETERMINATE THYROID NODULES.

Objective: Thyroid nodules with indeterminate cytology pose management challenges in clinical practice. The aim of this study was to determine the efficacy of ultrasound features in navigating clinical decision making in thyroid nodules with indeterminate cytology. Methods: We retrospectively reviewed ultrasound imaging from 186 adult patients with thyroid nodules and indeterminate cytology who underwent thyroidectomy at a quaternary hospital from 2010-2017. All nodules were classified based on the American Thyroid Association (ATA) and 2017 American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS). Nodules were included if good quality pre-operative ultrasound imaging and surgical pathology were available. Results: A total of 202 thyroid nodules were included. The median age was 57 years; 82.8% were female. Risk of malignancy (ROM) in resected nodules with Bethesda 3 and 4 cytology was 19.4% and 30.3%, respectively. ATA high-suspicious and TI-RADS 5 nodules had high ROM, 100% in both systems for Bethesda 3 nodules; 66.7% and 50.0%, respectively, for Bethesda 4 nodules. For ATA very-low suspicious/TI-RADS 1 and 2, ROM was 0%. ROM in ATA low-suspicious/TI-RADS 3 nodules with Bethesda 3 cytology was lower (15.2% and 16.0%, respectively) than Bethesda 4 cytology (33.8% and 34.3%, respectively). ATA intermediate-suspicious/TI-RADS 4 nodules with Bethesda 4 cytology had a lower ROM (11.1% and 18.2%, respectively) than Bethesda 3 cytology (28.6 % and 31.6%, respectively). Conclusion: Using either the ATA or the TI-RADS system to risk-stratify nodules with indeterminate cytology may help clinicians plan better for additional diagnostic testing and treatment. Abbreviations: ACR = American College of Radiology; ATA = American Thyroid Association; AUS = atypia of undetermined significance; FLUS = follicular lesion of undetermined significance; FN = follicular neoplasm; PPV = positive predictive value; ROM = risk of malignancy; SFN = suspicious for follicular neoplasm; TI-RADS = Thyroid Imaging Reporting and Data System.

Impact of Micro- and Macroscopically Positive Surgical Margins on Survival after Resection of Adrenocortical Carcinoma.

PURPOSE: Adrenocortical carcinoma (ACC) is a rare, aggressive cancer; complete surgical resection offers the best chance for long-term survival. The impact of surgical margin status on survival is poorly understood. Our objective was to determine the association of margin status with survival. METHODS: Patients with ACC were identified from the National Cancer Data Base, 1998-2012, and stratified based on surgical margin status (negative vs. microscopically positive [+] vs. macroscopically [+]). Univariate/multivariate regression/survival analyses were utilized to determine factors associated with margin status and overall survival (OS). RESULTS: A total of 1553 patients underwent surgery at 589 institutions: 86% had negative, 12% microscopically (+), and 2% macroscopically (+) margins. Those with microscopically (+) and macroscopically (+) margins more often received adjuvant chemotherapy (39.4% macroscopically (+) vs. 38.5% microscopically (+) vs. 25.2% negative margins, p < 0.001). For unadjusted analysis, there was a significant difference in OS between the groups (log-rank p < 0.001), with median survival times of 58 months (95% confidence interval [CI] 49-66) for those with negative margins, 22 months (95% CI 18-34) microscopically (+), and 14 months (95% CI 6-27) macroscopically (+) margins. After adjustment, both microscopically (+) (HR 1.76, p < 0.001) and macroscopically (+) (HR 2.10, p = 0.0019) margin status were associated with compromised survival. CONCLUSIONS: Having micro- or macroscopically (+) margin status after ACC resection is associated with dose-dependent compromised survival. These results underscore the importance of achieving negative surgical margins for optimizing long-term patient outcomes.

Is There a Minimum Number of Thyroidectomies a Surgeon Should Perform to Optimize Patient Outcomes?

OBJECTIVE: To determine the number of total thyroidectomies per surgeon per year associated with the lowest risk of complications. BACKGROUND: The surgeon volume-outcome association has been established for thyroidectomy; however, a threshold number of cases defining a "high-volume" surgeon remains unclear. METHODS: Adults undergoing total thyroidectomy were identified from the Health Care Utilization Project-National Inpatient Sample (1998-2009). Multivariate logistic regression with restricted cubic splines was utilized to examine the association between the number of annual total thyroidectomies per surgeon and risk of complications. RESULTS: Among 16,954 patients undergoing total thyroidectomy, 47% had thyroid cancer and 53% benign disease. Median annual surgeon volume was 7 cases; 51% of surgeons performed 1 case/y. Overall, 6% of the patients experienced complications. After adjustment, the likelihood of experiencing a complication decreased with increasing surgeon volume up to 26 cases/y (P < 0.01). Among all patients, 81% had surgery by low-volume surgeons (≤25 cases/y). With adjustment, patients undergoing surgery by low-volume surgeons were more likely to experience complications (odds ratio 1.51, P = 0.002) and longer hospital stays (+12%, P = 0.006). Patients had an 87% increase in the odds of having a complication if the surgeon performed 1 case/y, 68% for 2 to 5 cases/y, 42% for 6 to 10 cases/y, 22% for 11 to 15 cases/y, 10% for 16 to 20 cases/y, and 3% for 21 to 25 cases/y. CONCLUSIONS: This is the first study to identify a surgeon volume threshold (>25 total thyroidectomies/y) that is associated with improved patient outcomes. Identifying a threshold number of cases defining a high-volume thyroid surgeon is important, as it has implications for quality improvement, criteria for referral and reimbursement, and surgical education.

Leptin Is Produced by Parathyroid Glands and Stimulates Parathyroid Hormone Secretion.

OBJECTIVE: We asked if leptin and its cognate receptor were present in normal and diseased parathyroid glands, and if so, whether they had any functional effects on parathyroid hormone (PTH) secretion in parathyroid neoplasms. BACKGROUND: The parathyroid glands acting through PTH play a critical role in the regulation of serum calcium. Based on leptin's recently discovered role in bone metabolism, we hypothesized these glands were the sites of a functional interaction between these 2 hormones. METHODS: From July 2010 to July 2011, 96 patients were enrolled in a prospective study of leptin and hyperparathyroidism, all of whom were enrolled based on their diagnosis of hyperparathyroidism, and their candidacy for surgical intervention provided informed consent. Immediately after parathyroidectomy, 100 to 300 mg of adenomatous or hyperplastic diseased parathyroid tissue was prepared and processed according to requirements of the following: in situ hybridization, immunohistochemistry, immunofluorescence by conventional and spinning disc confocal microscopy, electron microscopy, parathyroid culture, whole organ explant, and animal model assays. RESULTS: Leptin, leptin receptor (long isoform), and PTH mRNA transcripts and protein were detected in an overlapping fashion in parathyroid chief cells in adenoma and hyperplastic glands, and also in normal parathyroid by in situ hybridization, qRT-PCR, and immunohistochemistry. Confocal microscopy confirmed active exogenous leptin uptake in cultured parathyroid cells. PTH secretion in explants increased in response to leptin and decreased with leptin receptor signaling inhibition by AG490, a JAK2/STAT3 inhibitor. Ob/ob mice injected with mouse leptin exhibited increased PTH levels from baseline. CONCLUSIONS: Taken together, these data suggest that leptin is a functionally active product of the parathyroid glands and stimulates PTH release.

The Impact of Pathologically Positive Lymph Nodes in the Clinically Negative Neck: An Analysis of 39,301 Patients with Papillary Thyroid Cancer.

PURPOSE: Management of patients with low-risk papillary thyroid cancer (PTC) with clinically uninvolved lymph nodes (cN0 LNs), but who harbor metastatic central LNs (pN1a), remains unclear. The number of central LNs examined, radioactive iodine (RAI) utilization, and survival were compared across cN0 patients based on pN stage: pN0 (negative) versus pNx (unknown) versus pN1a (pathologically positive). METHODS: Adults with a PTC ≥1 cm who were cN0 preoperatively were compared based on surgical pathology using the National Cancer Data Base (NCDB; 2003-2011), after univariate and multivariate adjustment. Overall survival (OS) was examined using Kaplan-Meier curves, the log-rank test, and Cox proportional hazards modeling. RESULTS: Overall, 39,301 patients were included; median tumor size was 1.9 cm. More LNs were examined for pN1a versus pN0 diagnosis (pN1a median = 5 LNs vs. pN0 median = 2 LNs; p < 0.0001), with a median of two central LNs found to be positive on surgical resection. Compared with pN0, pN1a patients were 78% more likely to receive RAI (odds ratio 1.78, 95% confidence interval [CI] 1.65-1.91; p < 0.0001). After adjusting for receipt of RAI, no difference in OS was observed for pN1a versus pN0 or pNx patients (p = 0.72). Treatment with RAI was associated with improved OS (hazard ratio 0.78, 95% CI 0.62-0.98, p = 0.03), but the effect of RAI did not differ based on pN stage (interaction p = 0.67). CONCLUSION: More LNs were examined for positive versus negative pN diagnosis in patients with cN0 PTC. Unsuspected central neck nodal metastases in cN0 PTC patients are associated with increased RAI utilization, but no survival difference.

Nationwide trends and outcomes associated with neoadjuvant therapy in pancreatic cancer: An analysis of 18 243 patients.

BACKGROUND: Neoadjuvant therapy has theoretical benefits for pancreatic cancer; however, its association with perioperative outcomes remains controversial. This study sought to evaluate variation in use of neoadjuvant therapy and outcomes following pancreatic resection. METHODS: The National Cancer Data Base (1998-2011) was queried for patients with Stage I or II pancreatic adenocarcinoma who underwent pancreaticoduodenectomy. Subjects were classified by use of neoadjuvant chemotherapy and/or radiation therapy. Factors associated with use of neoadjuvant therapy were evaluated, and outcomes were compared. RESULTS: A 18 243 patients were identified; 1375 (7.5%) received neoadjuvant therapy. From 1998 to 2011, use of neoadjuvant therapy increased from 4.3% to 17.0%. Patients receiving neoadjuvant therapy were younger (63.1 vs 66.1 years, P = 0.001) and more likely to receive treatment at an academic facility (64.4% vs 51.4%, P < 0.001). Patients who received neoadjuvant therapy were more likely to have negative margins (77.8% vs 85.5%), negative lymph nodes (42.9% vs 59.3%) and tumors confined to the pancreas (65.8% vs 70.6%, all P < 0.001). Patients receiving neoadjuvant therapy had lower 30-day mortality (2.0% vs 4.6%, P < 0.001) and readmission rates (7.4% vs 9.5%, P = 0.02). CONCLUSIONS: Neoadjuvant therapy use is increasing and associated with comparable short-term outcomes. Further studies are needed to identify patients who would benefit from neoadjuvant therapy.

Treatment trends and survival effects of chemotherapy for hypopharyngeal cancer: Analysis of the National Cancer Data Base.

BACKGROUND: The current study was performed to characterize trends and survival outcomes for chemotherapy in the definitive and adjuvant treatment of hypopharyngeal cancer in the United States. METHODS: A total of 16,248 adult patients diagnosed with primary hypopharyngeal cancer without distant metastases between 1998 and 2011 were identified in the National Cancer Data Base. The association between treatment modality and overall survival was analyzed using Kaplan-Meier survival curves and 5-year survival rates. A multivariate Cox regression analysis was performed on a subset of 3357 cases to determine the treatment modalities that predict improved survival when controlling for demographic and clinical factors. RESULTS: There was a significant increase in the use of chemotherapy with radiotherapy both as definitive treatment (P<.001) and as adjuvant chemoradiotherapy with surgery (P=.001). This was accompanied by a decrease in total laryngectomy/pharyngectomy rates (P<.001). Chemoradiotherapy was associated with improved 5-year survival compared with radiotherapy alone in the definitive setting (31.8% vs 25.2%; log rank P<.001). Similarly, in multivariateanalysis, definitive radiotherapy was found to be associated with compromised survival compared with definitive chemoradiotherapy (hazard ratio, 1.51; P<.001). CONCLUSIONS: Survival analysis revealed that overall 5-year survival rates were higher for chemoradiotherapy compared with radiotherapy alone in the definitive setting, but were comparable between surgery with chemoradiotherapy and surgery with radiotherapy. Cancer 2016;122:1853-60. © 2016 American Cancer Society.