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.

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.

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.

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.

Proposing prognostic thresholds for lymph node yield in clinically lymph node-negative and lymph node-positive cancers of the oral cavity.

BACKGROUND: Prognostic lymph node yield thresholds have been identified and incorporated into treatment guidelines for multiple cancer sites, but not for oral cancer. The objective of this study was to identify optimal thresholds in elective and therapeutic neck dissection for oral cavity cancers. METHODS: Patients with oral cavity cancers in the National Cancer Database (NCDB) were stratified into clinically lymph node-negative (cN0) and clinically lymph node-positive (cN+) cohorts to reflect the differing surgical management for these diseases. Univariate and multivariate analyses were performed to assess the relation between lymph node yield and overall survival, adjusting for other prognostic factors. Thresholds derived from the NCDB were validated in the Surveillance, Epidemiology, and End Results database. RESULTS: In patients with cN0 cancers of the oral cavity from the NCDB, those who had <16 lymph nodes had significantly decreased survival. The proportion of positive lymph nodes was higher for patients who had ≥16 lymph nodes (27.2% vs 16.3% for < 16 lymph nodes; P < .001). This threshold was validated in 2715 lymph node-negative cancers from SEER, with a mortality hazard ratio of 0.825 for ≥ 16 lymph nodes (95% confidence interval, 0.764-0.950; P = .004). In patients with cN + oral cavity cancers from the NCDB, groups with <26 lymph nodes had significantly decreased survival. This threshold was validated in 1903 lymph node-positive cancers from SEER, with a mortality hazard ratio of 0.791 (95% confidence interval, 0.692-0.903; P = .001). Academic centers, higher volume centers, and geographic location predicted higher lymph node yields. CONCLUSIONS: More extensive neck dissection (≥16 lymph nodes in cN0, ≥ 26 lymph nodes in cN+) was associated with better survival. Further evaluation of practice patterns in lymph node yield may represent an opportunity for improved quality of care. Cancer 2016;122:3624-31. © 2016 American Cancer Society.

Current management of pediatric thyroid disease and differentiated thyroid cancer.

PURPOSE OF REVIEW: In this article, we focus on the role of ultrasound and fine needle aspiration, management of benign nodules, extent of thyroid resection, management of regional lymph node disease, and risk stratification in staging for well differentiated thyroid cancer (DTC) in children. RECENT FINDINGS: The recent guidelines by the American Thyroid Association focused specifically on the management of thyroid nodules and DTC in children and adolescents marks a change from previous versions, which extrapolated adult guidelines to the pediatric population. DTC in children has a distinct presentation and clinical behavior compared with adult disease. The overall excellent outcomes for pediatric patients have led to a risk stratification approach in their management (low, intermediate, and high-risk disease groupings), aiming to minimize the potential morbidity of treatment. SUMMARY: In this review, we focus on pediatric thyroid disease, including recent studies and debates regarding the management of thyroid nodules and DTC.

Patients Treated at Low-Volume Centers have Higher Rates of Incomplete Resection and Compromised Outcomes: Analysis of 31,129 Patients with Papillary Thyroid Cancer.

BACKGROUND: Data on the importance of margin status after total thyroidectomy for papillary thyroid cancer (PTC) remain limited. This study sought to identify factors associated with positive margins and to determine the impact of positive margins on survival for patients with PTC. METHODS: The National Cancer Data Base (1998-2006) was queried for patients with PTC who had undergone total thyroidectomy. The patients were divided into three groups based on margin status (negative, microscopically positive, and macroscopically positive). Patient demographic, clinical, and pathologic features were evaluated. A binary logistic regression model was developed to identify factors associated with positive margins. A Cox proportional hazards model was developed to identify factors associated with survival. RESULTS: Of the 31,129 patients enrolled in the study, 91.3 % had negative margins, 8.1 % had microscopically positive margins, and 0.6 % had macroscopically positive margins. The patients with negative margins were younger and more likely to be female, white, covered by private insurance, and treated at an academic or high-volume center (p < 0.05). They had smaller tumors and were less likely to have advanced-stage disease. After multivariable adjustment, increasing patient age [odds ratio (OR) = 1.02; p < 0.01], government insurance (OR = 1.20; p < 0.01), and no insurance (OR = 1.34; p = 0.01) were associated with positive margins. Reception of surgery at a high-volume facility (OR = 0.72; p < 0.01) was protective. After multivariable adjustment, both microscopically [hazard ratio (HR), 1.49; p < 0.01] and macroscopically positive margins (HR = 2.38; p < 0.01) were associated with compromised survival. CONCLUSIONS: Several vulnerable patient populations have a higher risk of incomplete resection after thyroidectomy for PTC. High-risk thyroid cancer patients should be referred to high-volume centers to optimize outcomes.

Minimally Invasive Pancreaticoduodenectomy Does Not Improve Use or Time to Initiation of Adjuvant Chemotherapy for Patients With Pancreatic Adenocarcinoma.

BACKGROUND: The modifiable variable best proven to improve survival after resection of pancreatic adenocarcinoma is the addition of adjuvant chemotherapy. A theoretical advantage of minimally invasive pancreaticoduodenectomy (MI-PD) is the potential for greater use and earlier initiation of adjuvant therapy, but this benefit remains unproven. METHODS: The 2010-2012 National Cancer Data Base (NCDB) was queried for patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma. Subjects were classified as MI-PD versus open pancreaticoduodenectomy (O-PD). Baseline variables were compared between groups. The independent effect of surgical approach on the use and timing of adjuvant chemotherapy was estimated using multivariable regression analyses. RESULTS: For this study, 7967 subjects were identified: 1191 MI-PD (14.9%) and 6776 O-PD (85.1%) patients. Patients who underwent MI-PD were more likely to have been treated at academic hospitals. Otherwise, the groups had no baseline differences. In both the MI-PD and O-PD groups, approximately 50% of the patients received adjuvant chemotherapy, initiated at a median of 54 versus 55 days postoperatively (p = 0.08). After multivariable adjustment, surgical approach was not independently associated with use (odds ratio 1.00; p = 0.99) or time to initiation of adjuvant chemotherapy (-2.3 days; p = 0.07). Younger age, insured status, lower comorbidity score, higher tumor stage, and the presence of lymph node metastases were independently associated with the use of adjuvant chemotherapy. CONCLUSIONS: At a national level, MI-PD does not result in greater use or earlier initiation of adjuvant chemotherapy. As surgeons and institutions continue to gain experience with this complex procedure, it will be important to revisit this benchmark as a justification for its increasing use for patients with pancreatic cancer.

Minimally Invasive Versus Open Pancreaticoduodenectomy for Cancer: Practice Patterns and Short-term Outcomes Among 7061 Patients.

OBJECTIVES: To describe national practice patterns regarding utilization of minimally invasive pancreaticoduodenectomy (MIPD) and compare short-term outcomes with those following open pancreaticoduodenectomy for cancer. BACKGROUND: There is increasing interest in use of MIPD; however, published data are limited to single institutional experiences. METHODS: Adult patients undergoing pancreaticoduodenectomy were identified from the National Cancer Database, 2010-2011. Descriptive statistics and multivariable modeling were employed to characterize use of MIPD (laparoscopic or robotic) and compare short-term outcomes to those following open pancreaticoduodenectomy. RESULTS: A total of 7061 patients underwent pancreaticoduodenectomy: 983 had MIPD and 6078 had open procedures. The use of MIPD increased by 45% (179 cases) from 2010 to 2011. The majority of hospitals (92%) performing MIPD were low volume (≤ 10 cases/2 years). Factors independently associated with undergoing MIPD included fewer comorbidities, treatment at an academic institution, and a neuroendocrine tumor diagnosis (all P < 0.01). The unadjusted 30-day mortality rate was 5.1% for MIPD versus 3.1% after open surgery. For patients with adenocarcinoma, there were no differences between MIPD and open pancreaticoduodenectomy after multivariable adjustment in number of lymph nodes removed, rate of positive surgical margins, length of stay, or readmissions. However, 30-day mortality was higher for patients undergoing MIPD versus open surgery (odds ratio = 1.87, confidence interval: 1.25-2.80, P = 0.002). CONCLUSIONS: While there is increasing interest in employing MIPD for adenocarcinoma, its use is associated with increased 30-day mortality. The majority of hospitals performing MIPD were low volume. These results may suggest that MIPD is a complex procedure for which comprehensive protocols outlining criteria for implementation might be warranted to optimize patient safety.

Impact of Timeliness of Resection and Thyroidectomy Margin Status on Survival for Patients with Anaplastic Thyroid Cancer: An Analysis of 335 Cases.

BACKGROUND: Controversies regarding anaplastic thyroid cancer (ATC) surround aggressiveness of tumor resection in the presence of extrathyroidal extension and the impact of delayed surgery on patient survival. Our goal was to analyze the survival implications of complete and timely resections. METHODS: Adult patients with ATC were culled from the National Cancer Data Base for the years 2003-2006. Kaplan-Meier curves and Cox proportional hazard regression analyses were used for univariate and multivariate survival analyses, respectively. RESULTS: A total of 680 ATC patients were identified. In the surgical cohort (n = 335), the female-to-male ratio was 1.6:1; mean age was 68.6 years. Patients with ATCs were staged as IVA in 42.7 % of cases, IVB in 32.2 %, and IVC in 25.1 %. Median time from diagnosis to surgery was 15 days. Negative margin status was more often achieved in patients diagnosed with stage IVA disease (p < 0.001). Compared to surgical patients, those who did not receive thyroid resections were older and had a more advanced stage of disease (both p < 0.001). In multivariable analyses, positive margin status was associated with increased mortality in stage IVA ATC (p = 0.017) but had no survival impact in stages IVB and IVC (p > 0.05). After adjustment for possible confounders, increasing time from diagnosis to surgery was not found to be associated with compromised survival outcomes for any disease stage. CONCLUSIONS: Timely and aggressive surgical management should be pursued in patients with intrathyroidal disease; however, aggressive resections may not be recommended for patients with stage IVB and IVC disease when morbidity and operative risks outweigh the limited benefits of surgery.