Coexisting Papillary and Anaplastic Thyroid Cancer: Elucidating the Spectrum of Aggressive Behavior.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a rare and lethal form of thyroid cancer. Overall prognosis is unclear when it arises focally in a background of papillary thyroid cancer (PTC). Clinicopathologic features and outcomes of tumors with coexisting PTC and ATC histologies (co-PTC/ATC) were categorized. METHODS: The National Cancer Database was queried for histologic codes denoting PTC, ATC, and co-PTC/ATC, defined as Grade 4 PTC, diagnosed from 2004 to 2017. Clinicopathologic features, OS, and treatment outcomes were analyzed by histologic type. RESULTS: A total of 386,862 PTC, 763 co-PTC/ATC, and 3,880 ATC patients were identified. Patients with co-PTC/ATC had clinicopathologic features in-between those of PTC and ATC, including rates of tumor size >4 cm, extrathyroidal extension, and distant metastases. On multivariable Cox proportional hazards modeling, age >55 years, Charlson-Deyo score ≥2, positive lymph nodes, lymphovascular invasion, distant metastases, and positive surgical margins were associated with worse OS, whereas radioactive iodine (RAI) and external beam radiation therapy (EBRT) were associated with improved OS, irrespective of margin status. OS was worse for co-PTC/ATC than for PTC but better than for ATC and differed based on the presence or absence of "aggressive" tumor features, including lymph node positivity, lymphovascular invasion, distant metastases, and positive surgical margins. CONCLUSIONS: Survival of patients with co-PTC/ATC is dependent on the presence of aggressive clinicopathologic features and lies within a spectrum between that of PTC and ATC. Adjuvant RAI and EBRT treatment may be beneficial, even after R0 resection.

Risk factors for venous thromboembolism (VTE) after adrenalectomy for adrenal cortical neoplasms.

BACKGROUND: Incidence of venous thromboembolism (VTE) after adrenalectomy for adrenal cortical carcinoma (ACC) is unknown. Herein, we aim to identify the relative incidence and risk factors of VTE after adrenalectomy for ACC. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried to identify patients who underwent adrenalectomy for ACC, Cushing syndrome (CS), and benign adrenal cortical syndromes (BACS). Univariable and multivariable analyses were used to determine clinical characteristics, 30-day postoperative VTE occurrences, and associated risk factors. Khorana oncologic risk score (KRS) for VTE was calculated and compared between groups. RESULTS: A total of 5896 patients were analyzed: 576 ACC, 371 CS, and 4949 BACS. Postoperative VTE occurred 0.9%, with the highest rate occurring in ACC (2.6% ACC vs. 1.6% CS vs. 0.7% BACS, p < 0.001). Forty percent of VTEs in the ACC cohort were diagnosed postdischarge. ACC patients with KRS ≥ 2 had a 9.6% incidence of VTE (p = 0.007). Multivariable analysis identified increased age (p = 0.03), presence of adrenal cancer (p = 0.01), and KRS ≥ 2 (p = 0.005) as risk factors for VTE after adrenalectomy. CONCLUSIONS: Postoperative VTE after adrenalectomy occurs most frequently for ACC. ACC patients with increased age and/or Khorana score ≥2 should be considered for extended VTE prophylaxis.

Predicting Survival and Response to Treatment in Gastroesophageal Neuroendocrine Tumors: An Analysis of the National Cancer Database.

BACKGROUND: Neuroendocrine tumors (NETs) of the esophagus and stomach are rare neoplasms with variable behavior. We aim to describe their epidemiology and response to treatment. METHODS: NETs of the stomach and the esophagus were selected from the National Cancer Database (2004-2013) and classified by location. Survival analyses were performed with respect to tumor characteristics and treatment variables. RESULTS: NETs of the stomach (n = 2700; 92.8%) and esophagus (n = 210, 7.2%) were identified. Gastric cardia NETs had demographics and behavior similar to esophageal tumors and were associated with worse overall survival than NETs of the noncardia stomach independent of grade (p < 0.001). Poorly differentiated histology [hazard ratio (HR) 4.14, 95% confidence interval (CI) 2.26-7.57; p < 0.001] and distant metastases (HR 3.28, 95% CI 1.94-5.56; p < 0.001) were the greatest independent predictors of survival. For patients with poorly differentiated NETs, surgery was the only treatment to have benefit on overall survival (HR 0.38, 95% CI 0.27-0.54; p < 0.001) regardless of extent of disease. There was no additional benefit to adjuvant chemotherapy or radiation in patients undergoing resection (p = 0.39), even for patients with lymph node metastases (surgery alone versus surgery plus adjuvant therapy, p = 0.46), distant metastases (p = 0.19), or positive margins (p = 0.33). CONCLUSIONS: Esophageal and gastric cardia NETs have worse survival than those of the noncardia stomach. Surgery offers the only survival benefit for poorly differentiated tumors, with no additional survival advantage to adjuvant chemotherapy or radiation.

CHL1 expression differentiates Hürthle cell carcinoma from benign Hürthle cell nodules.

BACKGROUND AND OBJECTIVES: Hürthle cell carcinoma (HCC) is an unusual and relatively rare type of differentiated thyroid cancer. Currently, cytologic analysis of fine-needle aspiration biopsy is limited in distinguishing benign Hürthle cell neoplasms from malignant ones. The aim of this study was to determine whether differences in the expression of specific genes could differentiate HCC from benign Hürthle cell nodules by evaluating differential gene expression in Hürthle cell disease. METHODS: Eighteen benign Hürthle cell nodules and seven HCC samples were analyzed by whole-transcriptome sequencing. Bioinformatics analysis was carried out to identify candidate differentially expressed genes. Expression of these candidate genes was re-examined by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was quantified by immunohistochemistry. RESULTS: Close homolog of L1 (CHL1) was identified as overexpressed in HCC. CHL1 was found to have greater than 15-fold higher expression in fragments per kilobase million in HCC compared with benign Hurthle cell tumors. This was confirmed by qRT-PCR. Moreover, the immunoreactivity score of the CHL1 protein was significantly higher in HCC compared with benign Hürthle cell nodules. CONCLUSIONS: CHL1 expression may represent a novel and useful prognostic biomarker to distinguish HCC from benign Hürthle cell disease.

Laparoscopic Appendectomy: Minimally Invasive Surgery Training Improves Outcomes in Basic Laparoscopic Procedures.

BACKGROUND: To determine whether minimally invasive surgery (MIS) training improves outcomes in laparoscopic appendectomy, a procedure that is commonly performed in general surgery training. METHODS: Retrospective review was conducted of all patients undergoing laparoscopic appendectomy for suspected acute appendicitis between 2014 and 2015 at a single-center, tertiary-care academic institution. Patients operated on by MIS-trained surgeons (MIS group) were compared to those operated on by general surgeons (GS group). Single-incision and multiport laparoscopic appendectomies were included; open approach, known malignancy, and interval appendectomies were excluded. RESULTS: A total of 507 patients were included in the study: 181 patients in the MIS group and 326 in the GS group. There were no differences in patient demographics or medical comorbidities between groups and most patients were ASA class 1 or 2. Patients operated on by MIS-trained surgeons had significantly shorter operative time (43 min, IQR 32-60 vs. 58 min, IQR 44-81; p < 0.001) and fewer intra-operative adverse events (0/181 vs. 8/326, 2.5%; p = 0.03). There was no difference in number of postoperative adverse events between groups (6/181, 3.3% vs. 21/326, 6.4%; p = 0.13). In the MIS group, subgroup analysis of single-incision versus multiport appendectomy showed no differences in intra-operative or postoperative adverse events. On multivariable linear regression, lack of MIS training and traditional multiport approach had the greatest effects on prolonging operative time (11.2 and 12.8 min, respectively; p = 0.001). CONCLUSIONS: MIS fellowship improves operative metrics and patient outcomes even in basic laparoscopy.

Less is More: The Impact of Multidisciplinary Thyroid Conference on the Treatment of Well-Differentiated Thyroid Carcinoma.

BACKGROUND: In 2006, a multidisciplinary thyroid conference (MDTC) was implemented to better plan management of thyroid cancer patients at our institution. This study assessed the clinical impact of a MDTC on radioactive iodine (RAI) treatment patterns. METHODS: A prospective database (2003-2014) collected patient and tumor characteristics, RAI doses, and tumor recurrences. Patients treated with total thyroidectomy for differentiated thyroid carcinoma ≥1 cm were stratified based on American Thyroid Association (ATA) risk classification. RAI regimens were compared before initiation of MDTC (2003-2005, n = 88), after establishment of MDTC (2007-2009, n = 95), and after the release of 2009 ATA guidelines (2011-2014, n = 181). RAI doses were defined as low (≤75 mCi), intermediate (76-150 mCi), and high (>150 mCi). RESULTS: There was a significant decrease in the number of patients who received high-dose RAI after implementation of MDTC compared to before initiation of MDTC in the intermediate and high-risk patient groups (p = 0.04 and p < 0.01) without an associated increase in tumor recurrence (11 vs. 7%, p = 0.74). On multivariable analysis, presentation of a patient at MDTC was a negative predictor for receiving high-dose RAI (p = 0.002). As might be expected, there was also a significant decrease in use of RAI after the 2009 ATA guidelines were issued compared to after implementation of MDTC (p < 0.01). CONCLUSION: In conjunction with implementation of a thyroid malignancy multidisciplinary conference, we observed significantly decreased postoperative dosing of RAI without increased tumor recurrence. The 2009 ATA guidelines were associated with a further decrease in RAI administration. Treatment for patients with thyroid carcinoma is optimized by a multidisciplinary approach.

The Impact of Nodal Dissection on Staging in Adrenocortical Carcinoma.

BACKGROUND: The role of lymphadenectomy in adrenocortical carcinoma (ACC) is controversial, and formal lymph node (LN) dissection is not routine. We sought to determine the minimum number of LNs that must be examined to accurately identify a patient as node negative. METHODS: The National Cancer Database was used to identify patients diagnosed with ACC from 2004 to 2013 who underwent surgical resection. Patients with distant metastases, multivisceral resection, or missing surgical or lymphadenectomy data were excluded. The primary outcome was overall survival (OS). RESULTS: LNs were identified on histopathology in 156 patients. Of these, 35 (22%) had at least one positive LN. Positive LNs were associated with positive surgical margins (odds ratio [OR] 5.80, p = 0.002) and increasing LN yield (OR 1.06, p = 0.02). Overall, on Cox regression analysis, LN positivity (hazard ratio [HR] 3.02, p < 0.001) and positive surgical margins (HR 2.06, p = 0.048) independently predicted poor OS after controlling for other factors that may influence survival. LN(-) disease in patients with one to three LNs examined had poorer overall survival compared with when at least four LNs were examined (p = 0.02). None of the other patient, tumor, and treatment variables had any impact on OS of the LN(-) cohort. The likelihood of identifying nodal involvement was higher on examination of at least four LNs compared with examination of one to three LNs (30 vs. 16%, p = 0.03). CONCLUSIONS: LN positivity in ACC tumors independently predicts worse 5-year OS and a minimum of four LNs may be required to accurately determine LN negativity.

The impact of the robotic platform on assistant variability in complex gastrointestinal surgery.

BACKGROUND: Nissen fundoplication is considered an advanced minimally invasive procedure whether performed laparoscopically or robotically. In laparoscopic surgery, it is evident that assistant skill level impacts operative times. However, the robotic platform allows improved surgeon autonomy. We aimed to determine the impact of assistant training level on operative times in robotic Nissen fundoplication (RNF) and laparoscopic Nissen fundoplication (LNF). METHODS: A prospectively maintained Nissen database (2011-2016) from a single academic institution was utilized to collect patient characteristics, operative times, length of stay, intraoperative complications, postoperative complications, readmission rate, and assistant training level. Assistants were either postgraduate year-3 surgery residents defined as junior-level assistants or a minimally invasive surgery (MIS) fellow defined as senior-level assistants. RESULTS: There were 105 patients included in our analyses. When comparing postgraduate year-3 residents to MIS fellows performing LNF, the median operative time was significantly decreased when senior-level assistants were present in the LNF group, 85 (75-103) versus 129 (74-269) min, P = 0.02. In comparison, median operative times in the RNF group were independent of the assistant's level of training, 154 (71-300) versus 158 (101-215) min, P = 0.34. There were no significant differences in outcomes between the junior- and senior-level assistant cohorts for estimated blood loss, length of stay, postoperative complications, and 30-d readmission rates in either the LNF or RNF group. CONCLUSIONS: Assistant training level impacted operative time for LNF but not RNF. These differences are most likely attributed to increased autonomy of the operating surgeon afforded by the robotic platform reducing assistant variability.

Variability in CT imaging of blunt trauma among ED physicians, surgical residents, and trauma surgeons.

BACKGROUND: Trauma triage decisions can be influenced by both knowledge and experience. Consequently, there may be substantial variability in computed tomography (CT) scans desired by emergency medicine physicians, surgical chief residents, and attending trauma surgeons. We quantified this difference and studied the effects of each group's decisions on missed injuries, cost, and radiation exposure. METHODS: All blunt trauma activations at an urban level 1 trauma center were studied over a 6-mo period. Three months into the study, a pan-scan protocol was introduced. Prior to CT imaging, providers separately completed a survey that asked which CT scans were desired for each patient. Based on the completed surveys, hypothetical missed injuries, radiation exposure, and cost were determined. RESULTS: The variability in the number of CT scans desired by each of the three providers and the resulting cost and radiation exposure were not statistically significant. Substantial variability was predominantly seen in the indications for the desired scans, with the difference between proportions ranging from 3.1%-68.7%. Agreement among the three providers was highest for head and c-spine scans (80%-100%) and lowest for maxillary face (57%-80%) and chest scans (52%-74%). Overall, the missed injury rate was similar for all the providers; chief residents missed significantly more major injuries than trauma attendings during the pan-scan period (P = 0.03). CONCLUSIONS: Trauma training and level of training did not have a substantial effect on radiological decisions during the initial trauma assessment. This study sheds light on the growing uniformity among providers with regard to medical decision-making in the initial work-up of trauma.

Features of mixed medullary thyroid tumors: An NCDB analysis of clinicopathologic characteristics and survival.

BACKGROUND: Mixed medullary-papillary thyroid carcinoma (MMPTC) and mixed medullary-follicular thyroid carcinoma (MMFTC) are rare variants with little known regarding behavior and prognosis. METHODS: Using the National Cancer Database (NCDB), demographics, clinicopathologic features, treatment, and overall survival (OS) from patients with MMPTC and MMFTC were compared to more prevalent subtypes. RESULTS: There were 296,101 patients: 421 MMPTC (0.14%), 133 MMFTC (0.04%), 263,140 PTC (88.87%), 24,208 FTC (8.18%) and 8,199 MTC (2.77%). Compared to PTC, MMPTC and MMFTC patients were older (p < 0.001) with a higher Charlson-Deyo comorbidity index (p < 0.001). Mixed tumors exhibited lower rates of nodal disease but more distant metastases compared to PTC (p < 0.001). MMPTC demonstrated lower estimated 10-year OS than PTC and FTC (76.04%vs 89.04% and 81.95%,p < 0.001), yet higher than MTC (70.29%,p < 0.001). MMFTC had a worse OS compared to all groups (63.32%,p < 0.001). CONCLUSION: Patients with MMFTC had significantly worse OS compared to DTC, portending a worse prognosis.

Association of the Affordable Care Act with access to highest-volume centers for patients with thyroid cancer.

BACKGROUND: Disparities exist in access to high-volume surgeons, who have better outcomes after thyroidectomy. The association of the Affordable Care Act's Medicaid expansion with access to high-volume thyroid cancer surgery centers remains unclear. METHODS: The National Cancer Database was queried for all adult thyroid cancer patients diagnosed from 2010 to 2016. Hospital quartiles (Q1-4) defined by operative volume were generated. Clinicodemographics and adjusted odds ratios for treatment per quartile were analyzed by insurance status. An adjusted difference-in-differences analysis examined the association between implementation of the Affordable Care Act and changes in payer mix by hospital quartile. RESULTS: In total, 241,448 patients were included. Medicaid patients were most commonly treated at Q3-Q4 hospitals (Q3 odds ratios 1.05, P = .020, Q4 1.11, P < .001), whereas uninsured patients were most often treated at Q2-Q4 hospitals (Q2 odds ratios 2.82, Q3 2.34, Q4 2.07, P < .001). After expansion, Medicaid patients had lower odds of surgery at Q3-Q4 compared with Q1 hospitals (odds ratios Q3 0.82, P < .001 Q4 0.85, P = .002) in expansion states, but higher odds of treatment at Q3-Q4 hospitals in nonexpansion states (odds ratios Q3 2.23, Q4 1.86, P < .001). Affordable Care Act implementation was associated with increased proportions of Medicaid patients within each quartile in expansion compared with nonexpansion states (Q1 adjusted difference-in-differences 5.36%, Q2 5.29%, Q3 3.68%, Q4 3.26%, P < .001), and a decrease in uninsured patients treated at Q4 hospitals (adjusted difference-in-differences -1.06%, P = .001). CONCLUSIONS: Medicaid expansion was associated with an increased proportion of Medicaid patients undergoing thyroidectomy for thyroid cancer in all quartiles, with increased Medicaid access to high-volume centers in expansion compared with nonexpansion states.

Metagenomic Sequencing of the Gallbladder Microbiome: Bacterial Diversity Does Not Vary by Surgical Pathology.

INTRODUCTION: Alterations in the microbiome contribute to the pathogenesis of many gastrointestinal diseases. However, the composition of the microbiome in gallbladder disease is not well described. METHODS: We aimed to characterize the biliary microbiome in cholecystectomy patients. Bile and biliary stones were collected at cholecystectomy for a variety of surgical indications between 2017 and 2019. DNA was extracted and metagenomic sequencing was performed with subsequent taxonomic classification using Kraken2. The fraction of bacterial to total DNA reads, relative abundance of bacterial species, and overall species diversity were compared between pathologies and demographics. RESULTS: A total of 74 samples were obtained from 49 patients: 46 bile and 28 stones, with matched pairs from 25 patients. The mean age was 48 years, 76% were female, 29% were Hispanic, and 29% of patients had acute cholecystitis. The most abundant species were Klebsiella pneumoniae, Staphylococcus aureus, and Streptococcus pasteurianus. The bacterial fraction in bile and stone samples was higher in acute cholecystitis compared to other non-infectious pathologies (p < 0.05). Neither the diversity nor differential prevalence of specific bacterial species varied significantly between infectious and other non-infectious gallbladder pathologies. Multivariate analysis of the non-infectious group revealed that patients over 40 years of age had increased bacterial fractions (p < 0.05). CONCLUSIONS: Metagenomic sequencing permits characterization of the gallbladder microbiome in cholecystectomy patients. Although a higher prevalence of bacteria was seen in acute cholecystitis, species and diversity were similar regardless of surgical indication. Additional study is required to determine how the microbiome can contribute to the development of symptomatic gallbladder disease.

Metastatic pancreatic neuroendocrine tumors feature elevated T cell infiltration.

Pancreatic neuroendocrine tumors (PNETs) are malignancies arising from the islets of Langerhans. Therapeutic options are limited for the over 50% of patients who present with metastatic disease. We aimed to identify mechanisms to remodel the PNET tumor microenvironment (TME) to ultimately enhance susceptibility to immunotherapy. The TMEs of localized and metastatic PNETs were investigated using an approach that combines RNA-Seq, cancer and T cell profiling, and pharmacologic perturbations. RNA-Seq analysis indicated that the primary tumors of metastatic PNETs showed significant activation of inflammatory and immune-related pathways. We determined that metastatic PNETs featured increased numbers of tumor-infiltrating T cells compared with localized tumors. T cells isolated from both localized and metastatic PNETs showed evidence of recruitment and antigen-dependent activation, suggestive of an immune-permissive microenvironment. A computational analysis suggested that vorinostat, a histone deacetylase inhibitor, may perturb the transcriptomic signature of metastatic PNETs. Treatment of PNET cell lines with vorinostat increased chemokine CCR5 expression by NF-κB activation. Vorinostat treatment of patient-derived metastatic PNET tissues augmented recruitment of autologous T cells, and this augmentation was substantiated in a mouse model of PNET. Pharmacologic induction of chemokine expression may represent a promising approach for enhancing the immunogenicity of metastatic PNET TMEs.

Dual inhibition of BRAF and MEK increases expression of sodium iodide symporter in patient-derived papillary thyroid cancer cells in vitro.

BACKGROUND: The majority of papillary thyroid cancers are driven by acquired mutations typically in the BRAF or RAS genes that aberrantly activate the mitogen-activated protein kinase pathway. This process leads to malignant transformation, dedifferentiation, and a decrease in the expression of the sodium-iodide symporter (NIS; SLC5A5), which results in resistance to radioactive iodine therapy. We sought to determine whether inhibition of aberrant mitogen-activated protein kinase-signaling can restore NIS expression. METHODS: We prospectively developed cultures of papillary thyroid cancers derived from operative specimens and applied drug treatments for 24 hours. Samples were genotyped to identify BRAF and RAS mutations. We performed quantitative PCR to measure NIS expression after treatment. RESULTS: We evaluated 24 patient papillary thyroid cancer specimens; BRAFV600E mutations were identified in 18 out of 24 (75.0%); 1 patient tumor had an HRAS mutation, and the remaining 5 were BRAF and RAS wildtype. Dual treatment with dabrafenib and trametinib increased NIS expression (mean fold change 4.01 ± 2.04, P < .001), and single treatment with dabrafenib had no effect (mean fold change 0.98 ± 0.42, P = .84). Tumor samples that had above-median NIS expression increases came from younger patients (39 vs 63 years, P < .05). CONCLUSION: Dual treatment with BRAF and MEK inhibitors upregulated NIS expression, suggesting that this treatment regimen may increase tumor iodine uptake. The effect was greatest in tumor cells from younger patients.

Restructuring of a General Surgery Residency Program in an Epicenter of the Coronavirus Disease 2019 Pandemic: Lessons From New York City.

On March 1, 2020, the first case of coronavirus disease 2019 (COVID-19) was confirmed in New York, New York. Since then, the city has emerged as an epicenter for the ongoing pandemic in the US. To meet the anticipated demand caused by the predicted surge of patients with COVID-19, the Department of Surgery at NewYork-Presbyterian Hospital/Weill Cornell Medicine developed and executed an emergent restructuring of general surgery resident teams and educational infrastructure. The restructuring of surgical services described in this Special Communication details the methodology used to safely deploy the necessary amount of the resident workforce to support pandemic efforts while maintaining staffing for emergency surgical care, limiting unnecessary exposure of residents to infection risk, effectively placing residents in critical care units, and maintaining surgical education and board eligibility for the training program as a whole.

Insurance Status Is Associated with Extent of Treatment for Patients with Papillary Thyroid Carcinoma.

Background: Health insurance has been shown to be a key determinant in cancer care, but it is unknown as to what extent insurance status affects treatments provided to papillary thyroid cancer (PTC) patients. We hypothesized that insured patients with PTC would have lower-risk tumors at diagnosis and be more likely to receive adjuvant therapies at follow-up. Methods: The American College of Surgeons' National Cancer Database was queried to identify all patients diagnosed with PTCs >2 mm in size from 2004 to 2015. Patients were grouped according to insurance status, and frequency of high-risk features and microcarcinoma at diagnosis were assessed. Multivariable analyses were used to identify independent predictors of more extensive treatment: total thyroidectomy (vs. lobectomy), lymphadenectomy, and radioactive iodine (RAI). Results: There were 190,298 patients who met inclusion criteria; the majority of patients had private insurance (139,675 [73.4%]) and were female (144,824 [76.1%]). Uninsured patients, as compared with privately insured patients, had higher rates of extrathyroidal extension of their cancers (25.2% vs. 18.9%, p < 0.001), lymphovascular invasion (16.2% vs. 12.0%, p < 0.001), and positive margins on final pathology (16.0% vs. 12.2%, p < 0.001). Conversely, patients with private insurance were 51% more likely to have microcarcinomas at diagnosis (odds ratio [OR] = 1.51 [confidence interval {CI} 1.35-1.68], p < 0.001) than uninsured patients, controlling for demographic, socioeconomic, and hospital factors. Private insurance was an independent predictor for treatment with total thyroidectomy (OR = 1.18 [CI 1.01-1.37], p < 0.05), formal lymphadenectomy (OR = 1.22 [CI 1.09-1.36], p < 0.001), and adjuvant RAI therapy (OR = 1.35 [CI 1.18-1.54], p < 0.001) as compared with no insurance, adjusted for socioeconomic, demographic, hospital, and oncologic differences. Patients with Medicare or Medicaid were no more likely to receive these treatments than uninsured patients. Conclusions: Privately insured patients have less aggressive PTCs at diagnosis, and they are more likely to be treated with total thyroidectomy, lymphadenectomy, and RAI compared with uninsured patients. Clinicians should take caution to ensure proper referral and follow-up for under- and uninsured patients to reduce disparities in treatment.

UCHL1 loss alters the cell-cycle in metastatic pancreatic neuroendocrine tumors.

Loss of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) expression by CpG promoter hypermethylation is associated with metastasis in gastroenteropancreatic neuroendocrine tumors; however, the mechanism of how UCHL1 loss contributes to metastatic potential remains unclear. In this study, we first confirmed that loss of UCHL1 expression on immunohistochemistry was significantly associated with metastatic tumors in a translational pancreatic neuroendocrine tumor (PNET) cohort, with a sensitivity and specificity of 78% and 89%, respectively. To study the mechanism driving this aggressive phenotype, BON and QGP-1 metastatic PNET cell lines, which do not produce UCHL1, were stably transfected to re-express UCHL1. In vitro assays, RNA-sequencing, and reverse-phase protein array (RPPA) analyses were performed comparing empty-vector negative controls and UCHL1-expressing cell lines. UCHL1 re-expression is associated with lower anchorage-independent colony growth in BON cells, lower colony formation in QGP cells, and a higher percentage of cells in the G0/G1 cell-cycle phase in BON and QGP cells. On RPPA proteomic analysis, there was an upregulation of cell-cycle regulatory proteins CHK2 (1.2 fold change, p=0.004) and P21 (1.2 fold change, p=0.023) in BON cells expressing UCHL1; western blot confirmed upregulation of phosphorylated CHK2 and P21. There were no transcriptomic differences detected on RNA-Sequencing between empty-vector negative controls and UCHL1-expressing cell lines. In conclusion, UCHL1 loss correlates with metastatic potential in PNETs and its re-expression induces a less aggressive phenotype in vitro, in part by inducing cell-cycle arrest through post-translational regulation of phosphorylated CHK2. UCHL1 re-expression should be considered as a functional biomarker in detecting PNETs capable of metastasis.

Current controversies and future directions in the diagnosis and management of differentiated thyroid cancers.

Despite the development of novel diagnostic, surgical, and chemotherapeutic approaches to differentiated thyroid cancers (DTCs), the diagnosis and management of these tumors remains controversial. The most recent American Thyroid Association (ATA) guidelines, released in 2015, reflect a recent shift towards less aggressive management for patients with DTCs. However, many clinicians have expressed concern that more conservative management will put patients at risk for disease recurrence and metastasis. In particular, the management of indeterminate nodules on fine needle aspiration (with special attention to genetic and epigenetic markers of malignancy), the extent of surgery for known differentiated cancers, the role of adjuvant radioactive iodine (RAI) therapy, and novel targeted treatments with tyrosine kinase inhibitors (TKIs) represent current areas of uncertainty and opportunities for future research. In this review, we examine the current state of the art in these areas, and address some of the questions that remain.

Perioperative Outcomes of Laparoscopic and Robotic Revisional Bariatric Surgery in a Complex Patient Population.

BACKGROUND: Utilization of the robotic platform has become more common in bariatric applications. We aim to show that robotic revisional bariatric surgery (RRBS) can be safely performed in a complex patient population with perioperative outcomes equivalent to laparoscopic revisional bariatric surgery (LRBS). METHODS: Retrospective review was conducted of adult patients undergoing laparoscopic revisional bariatric surgery (LRBS) or robotic revisional bariatric surgery (RRBS) at our institution from September 2007 to December 2016. Patients undergoing planned two-stage bariatric procedures were excluded. RESULTS: A total of 84 patients who underwent LRBS (n = 66) or RRBS (n = 18) were included. The index operation was adjustable gastric banding (AGB) in 39/84 (46%), sleeve gastrectomy (VSG) in 23/84 (27%), Roux-en-Y gastric bypass (RYGB) in 13/84 (16%), and vertical banded gastroplasty (VBG) in 9/84 (11%). For patients undergoing conversion from AGB (n = 39), there was no difference in operative time, length of stay, or complications by surgical approach. For patients undergoing conversion from a stapled procedure (n = 45), the robotic approach was associated with a shorter length of stay (5.8 ± 3.3 vs 3.7 ± 1.7 days, p = 0.04) with equivalent operative time and post-operative complications. There were three leaks in the LRBS group and none in the RRBS group (p = 0.36). Major complications occurred in 3/39 (8%) of patients undergoing conversion from AGB and 2/45 (4%) of patients undergoing conversion from a stapled procedure (p = 0.53) with no difference by surgical approach. CONCLUSIONS: RRBS is associated with a shorter length of stay than LRBS in complex procedures and has at least an equivalent safety profile. Long-term follow-up data is needed.