Medullary thyroid cancer with RET V804M mutation: more indolent than expected?

BACKGROUND: Significant genotype-phenotype variability among multiple endocrine neoplasia type 2A patients with a RET V804M mutation has been reported. METHODS: Patients with a RET V804M mutation treated at a single center were identified (January 1996-December 2020). The baseline characteristics, operative details, pathology, biochemical, and long-term data were analyzed. RESULTS: There were 79 patients; none developed pheochromocytoma or hyperparathyroidism or died in the study period. The mean age was 41.5 years (range = 1.0-81.0 years); 46.8% were men. Of 68 surgical patients, 53 (77.9%) underwent total thyroidectomy and 15 (22.1%) underwent total thyroidectomy with central neck dissection with or without lateral neck dissection. Twenty-four patients had elevated preoperative calcitonin, of whom 12 underwent total thyroidectomy (median = 7.5; range = 5.0-237.0 pg/mL), 10 underwent total thyroidectomy + central neck dissection (median = 27.6; range = 5.1-147.0 pg/mL), and 2 underwent total thyroidectomy + central neck dissection + lateral neck dissection (median = 3182.0; range = 361.0-6003.0 pg/mL). Pathology was benign (27.9%), papillary thyroid cancer alone (1.5%), C-cell hyperplasia (23.5%), and medullary thyroid cancer (47.1%; median tumor size = 3.0 mm). Three patients had elevated calcitonin postoperatively (median follow-up time = 60.0 months). In adjusted modeling, a preoperative calcitonin >5 pg/mL was associated with having medullary thyroid cancer on final pathology (odds ratio = 13.3; 95% confidence interval, 3.2-56.3; P < .001). CONCLUSION: In this large United States cohort of surgical patients with a RET V804M mutation, most had indolent disease and were without classic multiple endocrine neoplasia type 2A features. Calcitonin >5 pg/mL may serve as a meaningful value to guide surveillance and timing of surgery.

Salvage Cryoablation for Local Recurrences of Thyroid Cancer Inseparable from the Trachea and Neurovascular Structures.

PURPOSE: To demonstrate safety, feasibility, and effectiveness of cryoablation of recurrent papillary thyroid cancer ineligible for reoperation because of scarring, eligible for focal ablation as defined within 2015 American Thyroid Association guideline sections C16 and C17. MATERIALS AND METHODS: With multidisciplinary consensus, cryoablation was performed with curative intent for 15 tumors in 10 patients between January 2019 and July 2021. Demographics, procedural details, and serial postprocedural imaging findings were analyzed. RESULTS: The mean age was 72.5 years (range, 57-88 years), and 80% of the patients were women. The tumors (mean size, 16 mm ± 6; range, 9-29 mm) received 1 session of cryoablation with 100% technical success. The mean and median postcryoablation tumor volumetric involution rates were 88% and 99%, respectively, with 9 (60%) of 15 tumors involuting completely or down to the scar and 6 (40%) involuting partially at the end of the study period. Tumor size did not increase after cryoablation (0% local progression rate). All tumors abutted the trachea, skin, and/or vascular structures, and hydrodissection failed in all cases because of scarring. The major adverse event rate was 20% (3/15), with 2 cases of voice change and 1 case of Horner syndrome; all resolved at 6 months with no permanent sequelae. No vascular, tracheal, dermal, or infectious adverse events occurred during a mean follow-up of 242 days (range, 114-627 days). One patient died at 386 days after cryoablation because of unrelated cholangiocarcinoma. CONCLUSIONS: Cryoablation of local recurrences of papillary thyroid cancer abutting the trachea and/or neurovascular structures in the setting of hydrodissection failure because of scarring yielded a mean volumetric involution of 88%, primary efficacy of 60%, and objective response rate of 100% with no local recurrences or permanent complications during a mean follow-up of 242 days. The secondary efficacy and longer-term outcomes remain forthcoming.

Guideline Adherence and Practice Patterns in the Management of Medullary Thyroid Cancer.

INTRODUCTION: Little is known about nationwide practice patterns for the management medullary thyroid cancer (MTC) in relation to the 2015 American Thyroid Association guidelines and their impact on survival. METHODS: Using the Surveillance, Epidemiology, and End Results Program database (2000-2018), MTC treatment patterns were evaluated in terms of adherence to the 2015 American Thyroid Association guidelines across three time periods (2000-2009, 2010-2015, and 2016-2018). Outcomes of interest were guideline concordance, treatment utilization trends, disease-specific survival (DSS), and overall survival (OS). RESULTS: A total of 3332 patients with MTC were identified. Of which, 53.8%, 33.2%, and 11.4% of patients had localized, regional, and distant disease, respectively. In patients with locoregional disease, the rate of guideline-concordant surgery improved over time from 63.0% in 2000-2009 to 76.0% in 2016-2018 (P < 0.001). Guideline-concordant care was associated with increased OS (HR = 1.85, 95% CI: 1.42-2.43, P < 0.001) in patients with localized disease and increased DSS (HR = 1.65, 95% CI: 1.01-2.54, P < 0.001) and OS (HR = 1.89, 95% CI: 1.35-2.58, P < 0.001) in patients with regional disease. The median OS and DSS in patients with distant disease were 31 and 55 mo, respectively, and the rate of chemotherapy use rose from 21.6% to 39.2% (P = 0.003). CONCLUSIONS: The rate of guideline-concordant surgery for locoregional MTC increased after guideline publication in 2015, with an observed prolongment in OS and DSS. Chemotherapy use among patients with distant disease has increased over time, but their prognosis remains variable.

Outcomes of concurrent parathyroidectomy and thyroidectomy among CESQIP surgeons.

BACKGROUND: Studies comparing endocrine-specific outcomes following parathyroidectomy (PTx) versus concurrent parathyroidectomy and thyroidectomy (PTx + Tx) are few. METHODS: 10,019 patients were selected from the Collaborative Endocrine Surgery Quality Improvement Program (2014-2019). Baseline characteristics and short-term (≤30 days) outcomes for PTx + Tx vs PTx patients were compared using bivariate and multivariable methods. RESULTS: PTx + Tx patients were more likely to experience clinical hypoparathyroidism (6.7% vs 0.5%, p < 0.001), recurrent laryngeal nerve transection, (0.4% vs 0.1%, p = 0.002) and hematoma requiring evacuation (1.0% vs 0.2%, p < 0.001). Readmissions and ED visits for hypocalcemia were more frequent after PTx + Tx vs PTx. Concurrent surgery was associated with an 8-fold increase in risk of short-term complications (Odds Ratio (OR): 8.0, 95% Confidence Interval (CI): 5.7-11.1, p < 0.001). CONCLUSIONS: Patients undergoing PTx + Tx have increased rates of postoperative complications, ED visits, and readmissions compared to patients undergoing parathyroidectomy alone. These findings could help guide surgeon-patient discussions on the risks of concurrent surgery.

Patient-Reported Outcomes Following Total Thyroidectomy for Graves' Disease.

Background: Graves' disease accounts for ∼80% of all cases of hyperthyroidism and is associated with significant morbidity and decreased quality of life. Understanding the association of total thyroidectomy with patient-reported quality-of-life and thyroid-specific symptoms is critical to shared decision-making and high-quality care. We estimate the change in patient-reported outcomes (PROs) before and after surgery for patients with Graves' disease to inform the expectations of patients and their physicians. Methods: PROs using the MD Anderson Symptom Inventory (MDASI) validated questionnaire were collected prospectively from adult patients with Graves' disease from January 1, 2015, to November 20, 2020, on a longitudinal basis. Survey responses were categorized as before surgery (≤120 days), short term after surgery (<30 days; ST), and long term after surgery (≥30 days; LT). Negative binomial regression was used to estimate the association of select covariates with PROs. Results: Eighty-five patients with Graves' disease were included. The majority were female (83.5%); 47.1% were non-Hispanic white and 35.3% were non-Hispanic black. The median thyrotropin (TSH) value before surgery was 0.05, which increased to 0.82 in ST and 1.57 in LT. In bivariate analysis, the Total Symptom Burden Score, a composite of all patient-reported burden, significantly reduced shortly after surgery (before surgery mean of 56.88 vs. ST 39.60, p < 0.001), demonstrating improvement in PROs. Furthermore, both the Thyroid Symptoms Score, including patient-reported thermoregulation, palpitations, and dysphagia, and the Quality-of-Life Symptom Score improved in ST and LT (thyroid symptoms, before surgery 13.88 vs. ST 8.62 and LT 7.29; quality of life, before surgery 16.16 vs. ST 9.14 and LT 10.04, all p < 0.05). After multivariate adjustment, the patient-reported burden in the Thyroid Symptom Score and the Quality-of-Life Symptom Score exhibited reduction in ST (thyroid symptoms, rate ratio [RR] 0.55, confidence interval [CI]: 0.42-0.72; quality of life, RR 0.57, CI: 0.40-0.81) and LT (thyroid symptoms, RR 0.59, CI: 0.44-0.79; quality of Life, RR 0.43, CI: 0.28-0.65). Conclusions: Quality of life and thyroid-specific symptoms of Graves' patients improved significantly from their baseline before surgery to both shortly after and longer after surgery. This work can be used to guide clinicians and patients with Graves' disease on the expected outcomes following total thyroidectomy.

Postoperative Surveillance in Older Adults With T1N0M0 Low-risk Papillary Thyroid Cancer.

BACKGROUND: The frequency and cost of postoperative surveillance for older adults (>65 y) with T1N0M0 low-risk papillary thyroid cancer (PTC) have not been well studied. METHODS: Using the SEER-Medicare (2006-2013) database, frequency and cost of surveillance concordant with American Thyroid Association (ATA) guidelines (defined as an office visit, ≥1 thyroglobulin measurement, and ultrasound 6- to 24-month postoperatively) were analyzed for the overall cohort of single-surgery T1N0M0 low-risk PTC, stratified by lobectomy versus total thyroidectomy. RESULTS: Majority of 2097 patients in the study were white (86.7%) and female (77.5%). Median age and tumor size were 72 y (interquartile range 68-76) and 0.6 cm (interquartile range 0.3-1.1 cm), respectively; 72.9% of patients underwent total thyroidectomy. Approximately 77.5% of patients had a postoperative surveillance visit; however, only 15.9% of patients received ATA-concordant surveillance. Patients who underwent total thyroidectomy as compared with lobectomy were more likely to undergo surveillance testing, thyroglobulin (61.7% versus 24.8%) and ultrasound (37.5% versus 29.2%) (all P < 0.01), and receive ATA-concordant surveillance (18.5% versus 9.0%, P < 0.001). Total surveillance cost during the study period was $621,099. Diagnostic radioactive iodine, ablation, and advanced imaging (such as positron emission tomography scans) accounted for 55.5% of costs ($344,692), whereas ATA-concordant care accounted for 44.5% of costs. After multivariate adjustment, patients who underwent total thyroidectomy as compared with lobectomy were twice as likely to receive ATA-concordant surveillance (adjusted odds ratio 2.0, 95% confidence interval: 1.5-2.8, P < 0.001). CONCLUSIONS: Majority of older adults with T1N0M0 low-risk PTC do not receive ATA-concordant surveillance; discordant care was costly. Total thyroidectomy was the strongest predictor of receiving ATA-concordant care.

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 selection and outcomes of laparoscopic transabdominal versus posterior retroperitoneal adrenalectomy among surgeons in the Collaborative Endocrine Surgery Quality Improvement Program (CESQIP).

BACKGROUND: Laparoscopic adrenalectomy can be performed using a transabdominal or posterior retroperitoneal approach. Choosing the optimal approach can be challenging. METHODS: Using data from the Collaborative Endocrine Surgery Quality Improvement Program (2014-2018), baseline patient characteristics and outcomes were compared with bivariate methods; univariate and multivariate analyses were used to estimate the association between operative approach and complication risk. RESULTS: Among 833 patients, 35.3% underwent posterior retroperitoneal. Median age was 54 years. Patients undergoing posterior retroperitoneal had lesser rates of body mass index >40 (9.2% vs 17.4%, P = .001), smaller nodules (median 2.4 vs 3.2 cm, P < .001), and more commonly right-sided nodules (46.6% vs 36.9%, P = .02). Posterior retroperitoneal was associated with a lesser rate of conversion to an open procedure (0.7% vs 4.1%, P = .004), less complications (3.1% vs 8.7%, P = .002), and shorter hospital stay (≤48 h: 92.2% vs 76.6%, P < .001), but a greater rate of capsular disruption (12.6% vs 7.6%, P = .02). For posterior retroperitoneal cases with capsular disruption, median nodule size was 2.2 cm, and 16.2% were metastatic tumors. After multivariate adjustment, posterior retroperitoneal was 2.2 times as likely to result in capsular disruption as transabdominal (95% confidence interval, 1.04-4.79, P = .04). CONCLUSION: This study revealed a greater rate for capsular disruption during posterior retroperitoneal even for small tumors. Our findings from the Collaborative Endocrine Surgery Quality Improvement Program (2014-2018) suggests that posterior retroperitoneal should be used selectively, especially when a malignancy is suspected.

Extent of surgery for low-risk thyroid cancer in the elderly: Equipoise in survival but not in short-term outcomes.

BACKGROUND: Total thyroidectomy is more common than lobectomy for low-risk papillary thyroid cancer, despite equipoise in survival. Because postoperative morbidity increases with age, we aimed to investigate how the extent of thyroidectomy affects short-term outcomes among older patients. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified patients aged ≥66 years who were treated between 1996 and 2011 for papillary thyroid cancer with tumors ≤2 cm in diameter. We used multivariable logistic regression to evaluate the effect of extent of surgery on complications, emergency-department visits, and unplanned readmissions. RESULTS: Among 3,341 selected patients, 77.3% were female, mean age was 72.9 years, and tumors averaged 0.8 cm in diameter. A total of 67.6% of patients underwent total thyroidectomy, and 32.4% underwent lobectomy. Total thyroidectomy was associated with complications (odds ratio = 1.99) and readmissions (odds ratio = 1.59; both P < 0.01). Complications were higher in female patients (odds ratio = 1.34), black patients (versus white patients, odds ratio = 1.65), and those with ≥2 comorbidities (vs 0, odds ratio = 1.43; all P < 0.01). Black patients and those with ≥2 comorbidities had more emergency-department visits (odds ratio = 1.50 and 1.92, respectively) and readmissions (odds ratio = 2.19 and 2.29, respectively; all P < 0.01). CONCLUSION: Total thyroidectomy for older adults with low-risk papillary thyroid cancer may lead to potentially avoidable complications and readmissions, particularly for black and female patients. In many cases, lobectomy may be a safer and less costly alternative.

The devil is in the details: Assessing treatment and outcomes of 6,795 patients undergoing remedial parathyroidectomy in the Collaborative Endocrine Surgery Quality Improvement Program.

BACKGROUND: Multi-institutional data describing remedial parathyroidectomy compared with index parathyroidectomy are scarce. METHODS: Using data in the Collaborative Endocrine Surgery Quality Improvement Program (2014-2017), baseline characteristics and outcomes of patients undergoing remedial parathyroidectomy versus index parathyroidectomy were examined using bivariate and multivariate methods. Rates of hypercalcemia and hypocalcemia at ≥ 180 days were assessed. RESULTS: Among 6,795 patients, 367 (5.4%) underwent remedial parathyroidectomy. A single localization study was done in 24.8% versus 26.9% of remedial parathyroidectomy versus index parathyroidectomy (P = .37). Patients undergoing remedial parathyroidectomy had higher rates of preoperative laryngoscopy (45.5% versus 6.2%, P < .001), intraoperative nerve monitoring (57.5% versus 34.5%, P < .001), and < 50% drop in hyperparathyroidism than those undergoing index parathyroidectomy (9.6% versus 3.3%, P < .001). Among patients with ≥ 180 days follow-up, none of the remedial parathyroidectomy versus three index parathyroidectomy patients (0.3%) had vocal cord dysfunction. Hypercalcemia rates for remedial parathyroidectomy and index parathyroidectomy were 10.5% versus 5.0 (P = .07), and hypocalcemia rates were 10.5% versus 2.4% (P < .001). After multivariate adjustment, failure to cure was 4.0 times more likely in remedial parathyroidectomy than index parathyroidectomy (P < .001). CONCLUSION: This is the first multi-institutional examination of remedial parathyroidectomy outcomes in the Collaborative Endocrine Surgery Quality Improvement Program. Nerve injury rates are low; high rates of hypercalcemia and hypocalcemia suggest potential opportunities to refine the preoperative and intraoperative management of patients undergoing remedial parathyroidectomy.

Gasless Transaxillary Endoscopic Thyroidectomy with Robotic Assistance: A High-Volume Experience in North America.

BACKGROUND: Since its introduction nine years ago, gasless transaxillary thyroidectomy with robotic assistance (RT) has achieved a relatively limited application in North America. This study aimed to assess the outcomes of RT in a recent large, diverse North American population. METHODS: Consenting patients were selected for the RT approach from November 2010 to July 2015 based on patient preference, and their perioperative data were retrospectively reviewed. RESULTS: Of 301 robotic thyroidectomies completed in 281 patients, 160 were total thyroidectomy and 141 were lobectomy. Women predominated (98.9%), with a mean age of 41 years (range 17-74 years) and a mean follow-up of 24 months (range 3-71 months). The mean body mass index (BMI) was 25.7 kg/m2 (range 17-44 kg/m2). However, 33.3% of patients had a BMI 25-29.9 kg/m2, 12.4% had a BMI 30-34.9 kg/m2, 3.5% had a BMI 35-39.9 kg/m2, and 0.7% had a BMI ≥40 kg/m2. Excluding 20 completion lobectomy, the indications for surgery were indeterminate cytology (53%), malignant cytology (10%), growth (18%), Graves' disease (12%), and other (5%). The mean size of the largest resected nodule was 2.5 cm (range 0.7-6.4 cm). Mean operating time for robotic lobectomy and total thyroidectomy was 81 and 109 minutes, respectively. One patient was converted to standard cervicotomy for failure to progress endoscopically. Complications included temporary dysphonia (6.0%), permanent recurrent laryngeal nerve deficit (1.3%), hypocalcemia (temporary 8.2%, permanent 1.1%), seroma (0.7%), and hematoma requiring reoperation (0.3%). Complications did not differ in patients with a BMI ≥25 kg/m2 compared to those with a BMI <25 kg/m2 or with respect to nodules >3 cm or surgery for Graves' thyroiditis. One patient developed grade II arm lymphedema ipsilateral to the axillary incision at two years, which resolved with conservative management. No patient had a surgical site infection or brachial plexopathy. Cancer was present histologically in 133 (48%) patients. Among 91 patients with cancer of the index nodule, 48.4% had papillary, 44.0% follicular variant papillary, 2.2% minimally invasive follicular carcinoma, and 5.5% minimally invasive Hürthle cell carcinoma. One patient had sclerosing variant thyroid paraganglioma. To date, all patients are without evidence of tumor recurrence. CONCLUSIONS: At a high-volume center, gasless transaxillary endoscopic thyroid surgery done with robotic assistance is a safe, efficient, and effective approach in a diverse North American patient population.

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.

Each procedure matters: threshold for surgeon volume to minimize complications and decrease cost associated with adrenalectomy.

BACKGROUND: An association has been suggested between increasing surgeon volume and improved patient outcomes, but a threshold has not been defined for what constitutes a "high-volume" adrenal surgeon. METHODS: Adult patients who underwent adrenalectomy by an identifiable surgeon between 1998-2009 were selected from the Healthcare Cost and Utilization Project National Inpatient Sample. Logistic regression modeling with restricted cubic splines was utilized to estimate the association between annual surgeon volume and complication rates in order to identify a volume threshold. RESULTS: A total of 3,496 surgeons performed adrenalectomies on 6,712 patients; median annual surgeon volume was 1 case. After adjustment, the likelihood of experiencing a complication decreased with increasing annual surgeon volume up to 5.6 cases (95% confidence interval, 3.27-5.96). After adjustment, patients undergoing resection by low-volume surgeons (<6 cases/year) were more likely to experience complications (odds ratio 1.71, 95% confidence interval, 1.27-2.31, P = .005), have a greater hospital stay (relative risk 1.46, 95% confidence interval, 1.25-1.70, P = .003), and at increased cost (+26.2%, 95% confidence interval, 12.6-39.9, P = .02). CONCLUSION: This study suggests that an annual threshold of surgeon volume (≥6 cases/year) that is associated with improved patient outcomes and decreased hospital cost. This volume threshold has implications for quality improvement, surgical referral and reimbursement, and surgical training.

Projecting Survival in Papillary Thyroid Cancer: A Comparison of the Seventh and Eighth Editions of the American Joint Commission on Cancer/Union for International Cancer Control Staging Systems in Two Contemporary National Patient Cohorts.

BACKGROUND: This study aims to compare the seventh and eighth editions of the American Joint Commission on Cancer/Union for International Cancer Control (AJCC/UICC) tumor, node, metastasis staging system for patients with papillary thyroid cancer (PTC) in two national patient cohorts. METHODS: Adult PTC patients undergoing surgery were selected from the Surveillance, Epidemiology and End Results (SEER) program (2004-2012) and the National Cancer Database (2004-2012). Staging criteria for the seventh and eighth AJCC/UICC editions were applied separately to each cohort. Survival probabilities were estimated using the Kaplan-Meier method. Multivariable Cox proportional hazards models were used to estimate the association of stage with survival in both settings. The Akaike information criterion was used to assess model performance. RESULTS: About 23% of patients were downstaged from the seventh to the eighth edition in SEER, while 24% were downstaged in the National Cancer Database. Disease-specific survival (DSS) and overall survival (OS) were significantly related to stage at diagnosis when using both the seventh and eighth editions of the AJCC/UICC staging system (p < 0.001). Patients classified into higher stages (III and IV) in the eighth edition showed a worse prognosis than those classified into similar stages in the seventh edition. After adjustment, PTC stages as defined by both editions were significantly associated with DSS and OS. With respect to both DSS and OS, the eighth edition PTC model appeared to be a better fit to the data (smaller Akaike information criterion values) compared to the seventh edition. CONCLUSION: Based on these large contemporary national cohorts, the eighth edition AJCC/UICC tumor, node, metastasis classification for PTC is superior to the seventh edition for predicting survival.

Subtotal vs. total parathyroidectomy with autotransplantation for patients with renal hyperparathyroidism have similar outcomes.

BACKGROUND: The optimal surgery for patients with renal hyperparathyroidism has been controversial, as either subtotal parathyroidectomy (subtotal PTX) or total parathyroidectomy with auto-transplantation (total PTX-AT) may be employed. METHODS: Adult patients having subtotal PTX or total PTX-AT for secondary hyperparathyroidism were identified from the American College of Surgeons National Surgical Quality Improvement Program, 2005-2013. RESULTS: Of 1130 patients, the majority (n = 765, 68%) underwent subtotal PTX. Total PTX-AT was associated with longer operative time (median 150 vs. 120 min, p < 0.001). Rates of complications, reoperation, readmission, and 30-day mortality were not significantly different. After adjustment, the odds of having a complication [OR 0.97, p = 0.88] and being readmitted within 30 days [OR 0.86 p = 0.62] were similar between the two procedures. Total PTX-AT was associated with prolonged hospital stay [Adjusted mean 5.0 vs. 4.1 days; (RR) 1.22, p < 0.001] compared to subtotal PTX. CONCLUSIONS: Subtotal PTX and total PTX-AT have similar rates of complications, readmission, and 30-day mortality, but subtotal PTX is less likely to have extended hospital stay. These findings have important cost implications for patients, payers, and hospitals.

Controversies in the Management of Low-Risk Differentiated Thyroid Cancer.

Controversy exists over optimal management of low-risk differentiated thyroid cancer. This controversy occurs in all aspects of management, including surgery, use of radioactive iodine for remnant ablation, thyroid hormone supplementation, and long-term surveillance. Limited and conflicting data, treatment paradigm shifts, and differences in physician perceptions contribute to the controversy. This lack of physician consensus results in wide variation in patient care, with some patients at risk for over- or undertreatment. To reduce patient harm and unnecessary worry, there is a need to design and implement studies to address current knowledge gaps.

Racial Disparities in Differentiated Thyroid Cancer: Have We Bridged the Gap?

BACKGROUND: Racial disparities in the management of differentiated thyroid cancer (DTC) exist in the United States. There is a paucity of data examining their temporal trends. It was hypothesized that racial disparities in care provided to patients with DTC have improved over the past 15 years. METHODS: Adult patients undergoing surgery for DTC were included from the National Cancer Data Base (1998-2012). Temporal trends in appropriate extent of thyroidectomy and radioactive iodine therapy (RAI) were described for different racial groups. Multivariable logistic regression models were employed to estimate the adjusted association of receipt of appropriate extent of surgery and RAI, specifically under- and over-treatment, among different racial groups. RESULTS: Among 282,043 DTC patients, 80.3% were non-Hispanic white (white), 8.1% Hispanic, 7.2% non-Hispanic black (black), and 4.4% Asian. Black versus white race/ethnicity was associated with lower odds of receiving appropriate surgery (odds ratio [OR] = 0.78 [confidence interval (CI) 0.71-0.87]; p < 0.001). Appropriate RAI treatment was higher in blacks (OR = 1.07 [CI 1.02-1.12]; p = 0.01) and lower for Hispanics (OR = 0.90 [CI 0.86-0.95]; p < 0.001) compared with whites. There was a higher likelihood of RAI under-treatment in minority groups (Hispanic OR = 1.27, black OR = 1.26, Asian OR = 1.25; p < 0.001), and a lower likelihood of RAI over-treatment (Hispanic OR = 0.89, black OR = 0.83, Asian OR = 0.79; p < 0.001) compared with whites. Over time, an increasing proportion of black and white patients underwent appropriate extent of thyroidectomy (1998 vs. 2012: 78% vs. 88% and 81% vs. 91%, respectively). Compared with 1998, fewer patients in 2012 were under-treated with RAI: whites (48% vs. 29%, respectively), blacks (51% vs. 33%), Hispanics (51% vs. 37%), and Asians (55% vs. 39%). The extent of RAI over-treatment increased (1998 vs. 2012): whites (1% vs. 4%), blacks (2% vs. 4%), Hispanics (2% vs. 4%), and Asians (2% vs. 3%), respectively. CONCLUSIONS: Appropriate utilization of surgery and RAI for DTC has improved over time. However, the proportion of patients receiving appropriate thyroid surgery is consistently lower for blacks compared with whites. RAI over-treatment increased for all races over the study period. Efforts are needed to standardize DTC care among minority patients.

Transiently expressed ATG16L1 inhibits autophagosome biogenesis and aberrantly targets RAB11-positive recycling endosomes.

The membrane source for autophagosome biogenesis is an unsolved mystery in the study of autophagy. ATG16L1 forms a complex with ATG12-ATG5 (the ATG16L1 complex). The ATG16L1 complex is recruited to autophagic membranes to convert MAP1LC3B-I to MAP1LC3B-II. The ATG16L1 complex dissociates from the phagophore before autophagosome membrane closure. Thus, ATG16L1 can be used as an early event marker for the study of autophagosome biogenesis. We found that among 3 proteins in the ATG16L1 complex, only ATG16L1 formed puncta-like structures when transiently overexpressed. ATG16L1+ puncta formed by transient expression could represent autophagic membrane structures. We thoroughly characterized the transiently expressed ATG16L1 in several mammalian cell lines. We found that transient expression of ATG16L1 not only inhibited autophagosome biogenesis, but also aberrantly targeted RAB11-positive recycling endosomes, resulting in recycling endosome aggregates. We conclude that transient expression of ATG16L1 is not a physiological model for the study of autophagy. Caution is warranted when reviewing findings derived from a transient expression model of ATG16L1.

Comparative characteristics of primary hyperparathyroidism in pediatric and young adult patients.

BACKGROUND: Primary hyperparathyroidism is rare in pediatric patients. Our study aim was to compare primary hyperparathyroidism in pediatric (<19 years) and young adult (19-29 years) patients. METHODS: A prospectively collected database from a single, high-volume institution was queried for all patients age <30 years who had initial parathyroidectomy for primary hyperparathyroidism yielding 126/4,546 (2.7%) primary hyperparathyroidism patients representing 39 pediatric and 87 young adult patients. Presenting symptoms, operative data, and postoperative course were compared for patients age 0-19 years and 20-29 years. RESULTS: Sporadic primary hyperparathyroidism was present in 81.7% and occurred less often in pediatric patients than young adult patients (74.4% vs 86.2%, P = .12). Among patients with hereditary primary hyperparathyroidism, multiple endocrine neoplasia type 1 was the most common type. Multiglandular disease was common in both pediatric (30.7%) and young adult (21.8%) patients. Following parathyroidectomy, 3 (2.3%) patients had permanent hypoparathyroidism and none had permanent recurrent laryngeal nerve paralysis. Biochemical cure at 6 months was equally likely in pediatric and young adult patients (97.1% vs 93.6%, P = .44) with comparable follow-up (78.4 months vs 69.1 months, P = .66) and rates of recurrent disease (5.9% vs 10.3%, P = .46). Recurrence was due to multiple endocrine neoplasia 1-related primary hyperparathyroidism in all cases. CONCLUSION: Although primary hyperparathyroidism is sporadic in most patients <19 years, they are more likely to have multiple endocrine neoplasia type 1-associated primary hyperparathyroidism (23%). Parathyroidectomy for primary hyperparathyroidism can be performed safely in pediatric patients with a high rate of cure. Follow-up for patients with hereditary disease is necessary.