Measuring Decision-Making During Thyroidectomy: Validity Evidence for a Web-Based Assessment Tool.

BACKGROUND: Errors in judgment during thyroidectomy can lead to recurrent laryngeal nerve injury and other complications. Despite the strong link between patient outcomes and intraoperative decision-making, methods to evaluate these complex skills are lacking. The purpose of this study was to develop objective metrics to evaluate advanced cognitive skills during thyroidectomy and to obtain validity evidence for them. METHODS: An interactive online learning platform was developed ( www.thinklikeasurgeon.com ). Trainees and surgeons from four institutions completed a 33-item assessment, developed based on a cognitive task analysis and expert Delphi consensus. Sixteen items required subjects to make annotations on still frames of thyroidectomy videos, and accuracy scores were calculated based on an algorithm derived from experts' responses ("visual concordance test," VCT). Seven items were short answer (SA), requiring users to type their answers, and scores were automatically calculated based on their similarity to a pre-populated repertoire of correct responses. Test-retest reliability, internal consistency, and correlation of scores with self-reported experience and training level (novice, intermediate, expert) were calculated. RESULTS: Twenty-eight subjects (10 endocrine surgeons and otolaryngologists, 18 trainees) participated. There was high test-retest reliability (intraclass correlation coefficient = 0.96; n = 10) and internal consistency (Cronbach's α = 0.93). The assessment demonstrated significant differences between novices, intermediates, and experts in total score (p < 0.01), VCT score (p < 0.01) and SA score (p < 0.01). There was high correlation between total case number and total score (ρ = 0.95, p < 0.01), between total case number and VCT score (ρ = 0.93, p < 0.01), and between total case number and SA score (ρ = 0.83, p < 0.01). CONCLUSION: This study describes the development of novel metrics and provides validity evidence for an interactive Web-based platform to objectively assess decision-making during thyroidectomy.

Prostate-specific membrane antigen-directed nanoparticle targeting for extreme nearfield ablation of prostate cancer cells.

Almost all biological therapeutic interventions cannot overcome neoplastic heterogeneity. Physical ablation therapy is immune to tumor heterogeneity, but nearby tissue damage is the limiting factor in delivering lethal doses. Multi-walled carbon nanotubes offer a number of unique properties: chemical stability, photonic properties including efficient light absorption, thermal conductivity, and extensive surface area availability for covalent chemical ligation. When combined together with a targeting moiety such as an antibody or small molecule, one can deliver highly localized temperature increases and cause extensive cellular damage. We have functionalized multi-walled carbon nanotubes by conjugating an antibody against prostate-specific membrane antigen. In our in vitro studies using prostate-specific membrane antigen-positive LNCaP prostate cancer cells, we have effectively demonstrated cell ablation of >80% with a single 30-s exposure to a 2.7-W, 532-nm laser for the first time without bulk heating. We also confirmed the specificity and selectivity of prostate-specific membrane antigen targeting by assessing prostate-specific membrane antigen-null PC3 cell lines under the same conditions (<10% cell ablation). This suggests that we can achieve an extreme nearfield cell ablation effect, thus restricting potential tissue damage when transferred to in vivo clinical applications. Developing this new platform will introduce novel approaches toward current therapeutic modalities and will usher in a new age of effective cancer treatment squarely addressing tumoral heterogeneity.

De novo thyroid cancer following solid organ transplantation-A 25-year experience at a high-volume institution with a review of the literature.

BACKGROUND AND OBJECTIVES: We investigated the rate, stage, and prognosis of thyroid cancer in patients after solid-organ transplantations, and compared this to the general population. METHODS: We performed a retrospective review of patients who developed thyroid cancer after a solid-organ transplantation between January 1988 and December 2013 at a high volume transplant center. Standardized Incidence Ratio's (SIR) were calculated. Additionally, a systematic review of the literature was performed. RESULTS: A total of 10,428 patients underwent solid organ transplantation. Eleven patients (11.4 per 100,000 person-years) developed thyroid cancer: six men and five women with a mean age at diagnosis of thyroid cancer of 58 years. Ten patients underwent surgery and had stage I thyroid cancer. One patient had recurrent disease after a mean follow-up time of 78 months. The SIR varied between 0.75 and 2.3. Seventeen studies were included in the systematic review with a SIR ranging from 2.5 to 35. CONCLUSION: Rate of thyroid cancer is not significantly higher in patients who underwent solid organ transplantation compared to general population. Stage at presentation and prognosis also appear to be similar to that of the general population. Post-transplant screening for thyroid cancer remains debatable; however, when thyroid cancer is discovered, treatment should be similar to that of non-transplant patients. J. Surg. Oncol. 2017;115:105-108. © 2017 Wiley Periodicals, Inc.

Measuring intra-operative decision-making during laparoscopic cholecystectomy: validity evidence for a novel interactive Web-based assessment tool.

BACKGROUND: Errors in judgment during laparoscopic cholecystectomy can lead to bile duct injuries and other complications. Despite correlations between outcomes, expertise and advanced cognitive skills, current methods to evaluate these skills remain subjective, rater- and situation-dependent and non-systematic. The purpose of this study was to develop objective metrics using a Web-based platform and to obtain validity evidence for their assessment of decision-making during laparoscopic cholecystectomy. METHODS: An interactive online learning platform was developed ( www.thinklikeasurgeon.com ). Trainees and surgeons from six institutions completed a 12-item assessment, developed based on a cognitive task analysis. Five items required subjects to draw their answer on the surgical field, and accuracy scores were calculated based on an algorithm derived from experts' responses ("visual concordance test", VCT). Test-retest reliability, internal consistency, and correlation with self-reported experience, Global Operative Assessment of Laparoscopic Skills (GOALS) score and Objective Performance Rating Scale (OPRS) score were calculated. Questionnaires were administered to evaluate the platform's usability, feasibility and educational value. RESULTS: Thirty-nine subjects (17 surgeons, 22 trainees) participated. There was high test-retest reliability (intraclass correlation coefficient = 0.95; n = 10) and internal consistency (Cronbach's α = 0.87). The assessment demonstrated significant differences between novices, intermediates and experts in total score (p < 0.01) and VCT score (p < 0.01). There was high correlation between total case number and total score (ρ = 0.83, p < 0.01) and between total case number and VCT (ρ = 0.82, p < 0.01), and moderate to high correlations between total score and GOALS (ρ = 0.66, p = 0.05), VCT and GOALS (ρ = 0.83, p < 0.01), total score and OPRS (ρ = 0.67, p = 0.04), and VCT and OPRS (ρ = 0.78, p = 0.01). Most subjects agreed or strongly agreed that the platform and assessment was easy to use [n = 29 (78 %)], facilitates learning intra-operative decision-making [n = 28 (81 %)], and should be integrated into surgical training [n = 28 (76 %)]. CONCLUSION: This study provides preliminary validity evidence for a novel interactive platform to objectively assess decision-making during laparoscopic cholecystectomy.

Characteristics of contralateral carcinomas in patients with differentiated thyroid cancer larger than 1 cm.

PURPOSE: Traditionally, total thyroidectomy has been advocated for patients with tumors larger than 1 cm. However, according to the ATA and NCCN guidelines (2015, USA), patients with tumors up to 4 cm are now eligible for lobectomy. A rationale for adhering to total thyroidectomy might be the presence of contralateral carcinomas. The purpose of this study was to describe the characteristics of contralateral carcinomas in patients with differentiated thyroid cancer (DTC) larger than 1 cm. METHODS: A retrospective study was performed including patients from 17 centers in 5 countries. Adults diagnosed with DTC stage T1b-T3 N0-1a M0 who all underwent a total thyroidectomy were included. The primary endpoint was the presence of a contralateral carcinoma. RESULTS: A total of 1313 patients were included, of whom 426 (32 %) had a contralateral carcinoma. The contralateral carcinomas consisted of 288 (67 %) papillary thyroid carcinomas (PTC), 124 (30 %) follicular variant of a papillary thyroid carcinoma (FvPTC), 5 (1 %) follicular thyroid carcinomas (FTC), and 3 (1 %) Hürthle cell carcinomas (HTC). Ipsilateral multifocality was strongly associated with the presence of contralateral carcinomas (OR 2.62). Of all contralateral carcinomas, 82 % were ≤10 mm and of those 99 % were PTC or FvPTC. Even if the primary tumor was a FTC or HTC, the contralateral carcinoma was (Fv)PTC in 92 % of cases. CONCLUSIONS: This international multicenter study performed on patients with DTC larger than 1 cm shows that contralateral carcinomas occur in one third of patients and, independently of primary tumor subtype, predominantly consist of microPTC.

Changing paradigms in the treatment of malignant pheochromocytoma.

BACKGROUND: Pheochromocytomas and paragangliomas are intra- and extra-adrenal neoplasms that are rarely malignant. The treatment of those that are malignant has remained a challenge because little was known about the molecular pathways involved in its malignant transformation. Recently, however, the genetic and molecular changes involved in malignant pheochromocytoma have come to be understood. METHODS: The authors review the recent literature about the changing treatment options for malignant pheochromocytomas and paragangliomas. RESULTS: Traditional treatments for malignant pheochromocytoma remain unsuccessful. With the advances made in genomics and proteomics, novel pathways in pheochromocytoma carcinogenesis are becoming the targets of new treatment strategies and show promising results. CONCLUSIONS: Although several studies and clinical trials show great promise for improving the treatment of pheochromocytomas and paragangliomas, the hope is that future collaborative efforts will allow for prospective clinical trials using an evidenced-based approach.

Defining the competencies for laparoscopic transabdominal adrenalectomy: An investigation of intraoperative behaviors and decisions of experts.

BACKGROUND: Safe performance of laparoscopic transabdominal adrenalectomy requires the application of a complex body of knowledge and skills, which are difficult to define, teach, and measure. This qualitative study aims to characterize expert behaviors, decisions, and other cognitive processes required to perform laparoscopic transabdominal adrenalectomy. METHOD: Hierarchical and cognitive task analyses for right and left laparoscopic transabdominal adrenalectomy were performed using semi-structured interviews and field observations of experts. Verbal data was supplemented with published literature, coded and thematically analyzed using constructivist grounded-theory by 2 independent reviewers. RESULTS: A conceptual framework was synthesized. Sixty-eight tasks, 46 cognitive behaviors, and 52 potential errors were identified and categorized into 8 procedural steps and 8 fundamental principles: anticipation, exposure, teamwork or communication, physiology, dissection techniques, oncologic margins, tactical modification, and error recovery. Experts emphasized the importance of creating a 3-dimensional mental model of the anatomy or pathology (eg, aberrant vessels, tumor location) that is consistently fine-tuned throughout the operation, with conscious awareness of danger zones (eg, medial arc). Despite variations in dissection techniques, experts highlighted 2 themes: macrodissection and microdissection, with emphasis on nonlinear motions and effective transitions between the 2 when appropriate. CONCLUSION: This study defines behaviors and competencies that are essential to performing laparoscopic transabdominal adrenalectomy effectively and safely.

Thyroid Nodule DNA Methylation Signatures: An Important Diagnostic Annotation.

Molecular profiling in thyroid cancer has made significant progress in part due to advances in somatic mutation profiling. Yet, differentiating benign from malignant thyroid nodules remains elusive. A unique set of DNA methylation signatures has the potential of improving thyroid cancer molecular diagnostics based on the DNA methylome.See related article by Yim et al., p. 544.

Clinical Outcomes After Unilateral Adrenalectomy for Primary Aldosteronism.

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

Unexpected discrepancies in hospital administrative databases can impact the accuracy of monitoring thyroid surgery outcomes in France.

OBJECTIVE: To determine the validity of hospital administrative databases compared to prospective collection of medical data assessing thyroid surgery complications. BACKGROUND: Administrative data are increasingly used to track surgical outcomes. METHODS: All patients undergoing thyroid surgery at three French university hospitals between April 2008 and April 2009 were prospectively included. Using diagnosis and procedural codes from hospital administrative database, we designed three indicators for measuring complications of thyroid surgery: recurrent laryngeal nerve palsy, postoperative hypoparathyroidism, and postoperative hemorrhage. Gold standard was obtained from a prospective collection of medical data after systematically screening each patient for the above-mentioned complications. Their ability to monitor surgical outcomes over time within individual hospitals was estimated using control charts. Spatial comparison between hospitals was performed by funnel plots. RESULTS: A total of 1909 patients were included. Complication rates extracted from administrative data were significantly lower compared to medical data (nerve palsy 2.4% vs. 6.7%, hypoparathyroidism 10.6% vs. 22.3%, p<0.0001). Indicator sensitivity was 30.4% for nerve palsy, 45.4% for hypoparathyroidism and 71.4% for postoperative hemorrhage. Corresponding positive predictive values were 84.4%, 95.1% and 68.2%. In two of the three hospitals, administrative data were not able to track temporal variations in complications rates. Regarding inter-hospital comparisons, 2 out of 3 hospitals were considered outliers according to administrative data despite having an average performance based on medical data. CONCLUSIONS: The ability of indicators extracted from administrative databases to measure thyroid surgery outcomes depends on the quality of underlying data coding. Validation in every center should be a prerequisite before implementing such metrics for tracking performance.

Selective strategy for intensive monitoring after pheochromocytoma resection.

BACKGROUND: Guidelines recommend 24-48 hours of intensive monitoring after resection of pheochromocytoma. However, many patients do not require it. The objective of this study is to identify preoperative risk factors associated with postoperative hemodynamic instability (HDI) so as to select patients who may not require intensive postoperative monitoring. METHODS: Medical records of patients undergoing pheochromocytoma resection over a 12-year period were reviewed. Postoperative HDI was defined as systolic blood pressure of >200 or <90, heart rate >110 or <50 or needing active resuscitation. RESULTS: We included 41 patients; 49% had postoperative HDI but only 34% had HDI > 6 hours. Risk factors for HDI were preoperative mean arterial pressure (MAP) > 100 mm Hg (14% vs 45%), norepinephrine/normetanephrine levels >3x normal (44 vs 82%), and resection of another solid organ (0 vs 20%). Avoidance of planned postoperative monitoring for low-risk patients would have reduced estimated costs by 34%. CONCLUSION: Fewer than one-half of patients undergoing resection for pheochromocytoma benefit from intensive monitoring. High preoperative MAP, high norepinephrine/normetanephrine levels, and concomitant resection of another organ are risk factors for postoperative HDI. After a 6-hour interval of postoperative stability, selective rather than routine use of intensive monitoring may be an efficient strategy for monitoring lower risk patients.

Engineering Multi-Walled Carbon Nanotube Therapeutic Bionanofluids to Selectively Target Papillary Thyroid Cancer Cells.

BACKGROUND: The incidence of papillary thyroid carcinoma (PTC) has risen steadily over the past few decades as well as the recurrence rates. It has been proposed that targeted ablative physical therapy could be a therapeutic modality in thyroid cancer. Targeted bio-affinity functionalized multi-walled carbon nanotubes (BioNanofluid) act locally, to efficiently convert external light energy to heat thereby specifically killing cancer cells. This may represent a promising new cancer therapeutic modality, advancing beyond conventional laser ablation and other nanoparticle approaches. METHODS: Thyroid Stimulating Hormone Receptor (TSHR) was selected as a target for PTC cells, due to its wide expression. Either TSHR antibodies or Thyrogen or purified TSH (Thyrotropin) were chemically conjugated to our functionalized Bionanofluid. A diode laser system (532 nm) was used to illuminate a PTC cell line for set exposure times. Cell death was assessed using Trypan Blue staining. RESULTS: TSHR-targeted BioNanofluids were capable of selectively ablating BCPAP, a TSHR-positive PTC cell line, while not TSHR-null NSC-34 cells. We determined that a 2:1 BCPAP cell:α-TSHR-BioNanofluid conjugate ratio and a 30 second laser exposure killed approximately 60% of the BCPAP cells, while 65% and >70% of cells were ablated using Thyrotropin- and Thyrogen-BioNanofluid conjugates, respectively. Furthermore, minimal non-targeted killing was observed using selective controls. CONCLUSION: A BioNanofluid platform offering a potential therapeutic path for papillary thyroid cancer has been investigated, with our in vitro results suggesting the development of a potent and rapid method of selective cancer cell killing. Therefore, BioNanofluid treatment emphasizes the need for new technology to treat patients with local recurrence and metastatic disease who are currently undergoing either re-operative neck explorations, repeated administration of radioactive iodine and as a last resort external beam radiation or chemotherapy, with fewer side effects and improved quality of life.

Cost-Effectiveness of Diagnostic Lobectomy Versus Observation for Thyroid Nodules >4 cm.

BACKGROUND: The management of thyroid nodules >4 cm with benign cytology after fine-needle aspiration biopsy (FNAB) is controversial. FNAB is associated with a high false-negative rate in this setting, and may result in a delayed diagnosis and management of thyroid cancer. However, the majority of these nodules are benign. Therefore, the objective of this study was to determine the cost-utility of observation versus surgical management for thyroid nodules >4 cm with benign cytology after FNAB. METHODS: A microsimulation model comparing routine thyroid lobectomy with observation for low-risk patients with >4 cm thyroid nodules with benign FNAB cytology was constructed. Costs, quality-adjusted life-years (QALYs), and life-years gained were calculated over a lifetime time horizon from a U.S. Medicare perspective. RESULTS: The proportion of patients undergoing thyroid lobectomy for benign final pathology was 40% in the observation strategy versus 66% in the surgical strategy (p < 0.001). Overall, the surgical strategy was associated with higher lifetime costs compared with the observation strategy (incremental difference: + US$12,992 [confidence interval (CI) 13,042-13,524]), but also more QALYs (+0.12 QALYs [CI 0.02-0.24]) and longer life expectancy (+1.67 years [CI 1.00-2.41]). Incremental lifetime costs were lower for patients <55 years compared with those ≥55 years (+11,181 vs. +14,811, p < 0.001). The probability of cost-effectiveness of the surgical strategy was 49% at a $100k/QALY threshold or 65% at a $100k/life-year gained threshold. CONCLUSIONS: Routine thyroid lobectomy is associated with improved outcomes at an acceptable cost compared with observation for thyroid nodules >4 cm with benign cytology after FNAB. Surgical resection may be a cost-effective strategy to rule out malignancy in these nodules.

Correction: Engineering Multi-Walled Carbon Nanotube Therapeutic Bionanofluids to Selectively Target Papillary Thyroid Cancer Cells.

[This corrects the article DOI: 10.1371/journal.pone.0149723.].

Risk Factors for Decreased Quality of Life in Thyroid Cancer Survivors: Initial Findings from the North American Thyroid Cancer Survivorship Study.

BACKGROUND: The prevalence of thyroid cancer survivors is rising rapidly due to the combination of an increasing incidence, high survival rates, and a young age at diagnosis. The physical and psychosocial morbidity of thyroid cancer has not been adequately described, and this study therefore sought to improve the understanding of the impact of thyroid cancer on quality of life (QoL) by conducting a large-scale survivorship study. METHODS: Thyroid cancer survivors were recruited from a multicenter collaborative network of clinics, national survivorship groups, and social media. Study participants completed a validated QoL assessment tool that measures four morbidity domains: physical, psychological, social, and spiritual effects. Data were also collected on participant demographics, medical comorbidities, tumor characteristics, and treatment modalities. RESULTS: A total of 1174 participants with thyroid cancer were recruited. Of these, 89.9% were female, with an average age of 48 years, and a mean time from diagnosis of five years. The mean overall QoL was 5.56/10, with 0 being the worst. Scores for each of the sub-domains were 5.83 for physical, 5.03 for psychological, 6.48 for social, and 5.16 for spiritual well-being. QoL scores begin to improve five years after diagnosis. Female sex, young age at diagnosis, and lower educational attainment were highly predictive of decreased QoL. CONCLUSION: Thyroid cancer diagnosis and treatment can result in a decreased QoL. The present findings indicate that better tools to measure and improve thyroid cancer survivor QoL are needed. The authors plan to follow-up on these findings in the near future, as enrollment and data collection are ongoing.

Cost-effectiveness of molecular testing for thyroid nodules with atypia of undetermined significance cytology.

CONTEXT: Novel molecular diagnostics, such as the gene expression classifier (GEC) and gene mutation panel (GMP) testing, may improve the management for thyroid nodules with atypia of undetermined significance (AUS) cytology. The cost-effectiveness of an approach combining both tests in different practice settings in North America is unknown. OBJECTIVE: The aim of the study was to determine the cost-effectiveness of two diagnostic molecular tests, singly or in combination, for AUS thyroid nodules. DESIGN AND SETTING: We constructed a microsimulation model to investigate cost-effectiveness from US (Medicare) and Canadian healthcare system perspectives. PATIENTS: Low-risk patients with AUS thyroid nodules were simulated. INTERVENTIONS: We examined five management strategies: 1) routine GEC; 2) routine GEC + selective GMP; 3) routine GMP; 4) routine GMP + selective GEC; and 5) standard management. MAIN OUTCOME MEASURES: Lifetime costs and quality-adjusted life-years were measured. RESULTS: From the US perspective, the routine GEC + selective GMP strategy was the dominant strategy. From the Canadian perspective, routine GEC + selective GMP cost and additional CAN$24 030 per quality-adjusted life-year gained over standard management, and was dominant over the other strategies. Sensitivity analyses reported that the decisions from both perspectives were sensitive to variations in the probability of malignancy in the nodule and the costs of the GEC and GMP. The probability of cost-effectiveness for routine GEC + selective GMP was low. CONCLUSIONS: In the US setting, the most cost-effective strategy was routine GEC + selective GMP. In the Canadian setting, standard management was most likely to be cost effective. The cost of these molecular diagnostics will need to be reduced to increase their cost-effectiveness for practice settings outside the United States.

Pheochromocytoma crisis is not a surgical emergency.

CONTEXT: Pheochromocytoma crisis is a feared and potentially lethal complication of pheochromocytoma. OBJECTIVE: We sought to determine the best treatment strategy for pheochromocytoma crisis patients and hypothesized that emergency resection is not indicated. DESIGN: Retrospective cohort study (1993-2011); literature review (1944-2011). SETTING: Tertiary referral center. PATIENTS: There were 137 pheochromocytoma patients from our center and 97 pheochromocytoma crisis patients who underwent adrenalectomy from the literature. INTERVENTION: Medical management of pheochromocytoma crisis; adrenalectomy. MAIN OUTCOME MEASURE(S): Perioperative complications, conversion, and mortality. RESULTS: In our database, 25 patients (18%) presented with crisis. After medical stabilization and α-blockade, 15 patients were discharged and readmitted for elective surgery and 10 patients were operated on urgently during the same hospitalization. None underwent emergency surgery. Postoperatively, patients who underwent elective surgery had shorter hospital stays (1.7 vs 5.7 d, P = 0.001) and fewer postoperative complications (1 of 15 [7%] vs 5 of 10 [50%], P = 0.045) and were less often admitted to the intensive care unit (1 of 15 [7%] vs 5 of 10 [50%], P = 0.045) in comparison with urgently operated patients. There was no mortality. Review of the literature (n = 97) showed that crisis patients who underwent elective or urgent surgery vs emergency surgery had less intraoperative (13 of 31 [42%] vs 20 of 25 [80%], P < 0.001) and postoperative complications (15 of 45 [33%] vs 15 of 21 [71%], P = 0.047) and a lower mortality (0 of 64 vs 6 of 33 [18%], P = 0.002). CONCLUSIONS: Management of patients presenting with pheochromocytoma crisis should include initial stabilization of the acute crisis followed by sufficient α-blockade before surgery. Emergency resection of pheochromocytoma is associated with high surgical morbidity and mortality.

A population-based prospective cohort study of complications after thyroidectomy in the elderly.

CONTEXT: Data on the risk of postthyroidectomy complications in elderly patients are sparse, unclear, and conflicting. OBJECTIVE: We sought to use a population-based cohort to determine whether thyroid operations in the elderly are as safe as those done in younger patients. DESIGN: This was a prospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program database from 2005 to 2008, with 30-d postoperative follow-up. SETTING: The American College of Surgeons National Surgical Quality Improvement Program data set contains operative cases from a nationwide sampling of academic and community-based as well as high-volume and low-volume hospitals. PATIENTS: All thyroidectomy and parathyroidectomy patients reported to the database during the study period were included in the analysis resulting in an experimental cohort of 7915 thyroidectomy cases and a control cohort of 3575 parathyroidectomy cases. MAIN OUTCOME MEASURES: We aggregated 83 complications into the following outcome measures: urinary tract infection, wound infection, systemic infection, cardiac complications, pulmonary complications, 30-d mortality, and total hospital length of stay. RESULTS: Increased age is a risk factor for significant pulmonary, cardiac, and infectious complications after thyroidectomy. Elderly patients are twice as likely (odds ratio 2.1, 95% confidence interval 1.4-3.3), and the superelderly are 5 times as likely (odds ratio 4.9, 95% confidence interval 2.5-9.6) to have a complication compared with their young counterparts. Preexisting comorbidities are effect modifiers and increase the risk of complications even further. CONCLUSIONS: Elderly thyroidectomy patients are at increased risk for major systemic complications. A systematic approach to the care of elderly thyroidectomy patients is necessary to minimize their risk of serious postoperative complications.

Modulation of matrix metalloproteinase activity in human thyroid cancer cell lines using demethylating agents and histone deacetylase inhibitors.

BACKGROUND: The purpose of this study was to investigate the effects of treating human thyroid cancer cell lines with demethylating agents and histone deacetylase (HDAC) inhibitors to see if they would downregulate expression and activity of the matrix metalloproteinases (MMP)-2 and MMP-9, resulting in inhibition of growth and invasion. METHODS: A total of 1 papillary cancer cell line (TPC-1) and 3 follicular thyroid cancer cell lines (FTC-133, FTC-236, and FTC-238) were treated with the demethylating agent 5-azacytidine (5-AZC) and the HDAC inhibitors trichostatin A (TSA) and valproic acid (VA). The activity of MMP proteins was determined using gelatin zymography, and commercially available assays were used to quantify growth inhibition and thyroid cancer cell invasion. RESULTS: Treatment with TSA and VA resulted in decreased protein activity of MMP-2 and MMP-9 in all cell lines in a dose-dependent manner after 48 hours of treatment compared with untreated controls. In addition, 5-, TSA, and VA caused inhibition of growth in the range of 25-80% for all cell lines at 24, 48, and 72 hours. VA and TSA significantly decreased cell invasion in the FTC-133 and TPC-1 cell lines. CONCLUSION: The HDAC inhibitors TSA and VA decreased the protein activity of MMP-2 and MMP-9 and, in combination with the demethylating agent 5-AZC, inhibited cellular growth in human papillary and follicular thyroid cancer cell lines. These results elucidate our understanding of the pathways affected by the demethylating agents and HDAC inhibitors, and provide further evidence that MMPs are a potentially useful target for molecular therapies in patients with aggressive or refractory thyroid cancers.