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A subset of thyroid cancers, recurrent differentiated thyroid cancers and anaplastic thyroid cancer (ATC), are difficult to treat by thyroidectomy and systemic therapy. A common mutation in thyroid cancer, BRAFV600E, has targetable treatment options; however, the results have been disappointing in thyroid cancers compared with BRAFV600E melanoma, as thyroid cancers quickly become resistant to BRAFV600E inhibitor (BRAFi). Here, we studied the molecular pathway that is induced in BRAFV600E thyroid cancer cells and patient-derived tumor samples in response to BRAFi, vemurafenib, using RNA-sequencing and molecular analysis. Both inducible response to BRAFi and acquired BRAFi resistance in BRAFV600E thyroid cancer cells showed significant activation of the JAK/STAT pathway. Functional analyses revealed that the combination of BRAFi and inhibitors of JAK/STAT pathway controlled BRAFV600E thyroid cancer cell growth. The Cancer Genome Atlas data analysis demonstrated that potent activation of the JAK/STAT signaling was associated with shorter recurrence rate in patients with differentiated thyroid cancer. Analysis of tumor RNA expression in patients with poorly differentiated thyroid cancer and ATC also support that enhanced activity of JAK/STAT signaling pathway is correlated with worse prognosis. Our study demonstrates that JAK/STAT pathway is activated as BRAFV600E thyroid cancer cells develop resistance to BRAFi and that this pathway is a potential target for anticancer activity and to overcome drug resistance that commonly develops to treatment with BRAFi in thyroid cancer. Implications: Dual inhibition of BRAF and JAK/STAT signaling pathway is a potential therapeutic treatment for anticancer activity and to overcome drug resistance to BRAFi in thyroid cancer.

S1. BRAFV600E mutation identified in thyroid cancer cell lines analyzed by RNA-seq.S2. STR analysis in thyroid cancer cell lines used in this study.S3. Gene expression of thyroid-specific genes in thyroid cancer cell lines analyzed by RNA-seq.S4. Dose-dependent toxicity of vemurafenib in BRAFV600E thyroidcancer cells.S5. Vemurafenib dose-dependent curves of vemurafenib-resistantBRAFV600E thyroid cancer cells.S6. Vemurafenib induces apoptosis in 8505C cells.S7. Predicted activators and inhibitors in Vem-resistant BRAF mutant thyroid cancer cells.

Supplementary Table 1. Gene expression changes in 8505C after vemurafenib treatment.Supplementary Table 2. Gene expression changes in WRO after vemurafenib treatment.Supplementary Table 3. Gene expression changes in 8505C -Vem-Res 1 relative to parental 8505C.Supplementary Table 4. Gene expression changes in WRO -Vem-Res 6 relative to parental WRO.Supplementary Table 5. Clinical features of thyroid tumors used in Fig. 5.

A subset of thyroid cancers, recurrent differentiated thyroid cancers and anaplastic thyroid cancer (ATC), are difficult to treat by thyroidectomy and systemic therapy. A common mutation in thyroid cancer, BRAFV600E, has targetable treatment options; however, the results have been disappointing in thyroid cancers compared with BRAFV600E melanoma, as thyroid cancers quickly become resistant to BRAFV600E inhibitor (BRAFi). Here, we studied the molecular pathway that is induced in BRAFV600E thyroid cancer cells and patient-derived tumor samples in response to BRAFi, vemurafenib, using RNA-sequencing and molecular analysis. Both inducible response to BRAFi and acquired BRAFi resistance in BRAFV600E thyroid cancer cells showed significant activation of the JAK/STAT pathway. Functional analyses revealed that the combination of BRAFi and inhibitors of JAK/STAT pathway controlled BRAFV600E thyroid cancer cell growth. The Cancer Genome Atlas data analysis demonstrated that potent activation of the JAK/STAT signaling was associated with shorter recurrence rate in patients with differentiated thyroid cancer. Analysis of tumor RNA expression in patients with poorly differentiated thyroid cancer and ATC also support that enhanced activity of JAK/STAT signaling pathway is correlated with worse prognosis. Our study demonstrates that JAK/STAT pathway is activated as BRAFV600E thyroid cancer cells develop resistance to BRAFi and that this pathway is a potential target for anticancer activity and to overcome drug resistance that commonly develops to treatment with BRAFi in thyroid cancer.Implications:Dual inhibition of BRAF and JAK/STAT signaling pathway is a potential therapeutic treatment for anticancer activity and to overcome drug resistance to BRAFi in thyroid cancer.

A model for ICAM1-CAR T and anti-PD1 antibody activities in advanced thyroid cancers.

Purpose:Advanced thyroid cancers, including poorly differentiated and anaplastic thyroid cancer (ATC), are lethal malignancies with limited treatment options. The majority of patients with ATC have responded poorly to programmed death 1 (PD1) blockade in early clinical trials. There is a need to explore new treatment options.Experimental Design:We examined the expression of PD-L1 (a ligand of PD1) and intercellular adhesion molecule 1 (ICAM1) in thyroid tumors and ATC cell lines, and investigated the PD1 expression level in peripheral T cells of patients with thyroid cancer. Next, we studied the tumor-targeting efficacy and T-cell dynamics of monotherapy and combination treatments of ICAM1-targeting chimeric antigen receptor (CAR) T cells and anti-PD1 antibody in a xenograft model of ATC.Results:Advanced thyroid cancers were associated with increased expression of both ICAM1 and PD-L1 in tumors, and elevated PD1 expression in CD8+ T cells of circulating blood. The expression of ICAM1 and PD-L1 in ATC lines was regulated by the IFNγ–JAK2 signaling pathway. ICAM1-targeted CAR T cells, produced from either healthy donor or patient T cells, in combination with PD1 blockade demonstrated an improved ability to eradicate ICAM1-expressing target tumor cells compared with CAR T treatment alone. PD1 blockade facilitated clearance of PD-L1 high tumor colonies and curtailed excessive CAR T expansion, resulting in rapid tumor clearance and prolonged survival in a mouse model.Conclusions:Targeting two IFNγ-inducible, tumor-associated antigens—ICAM1 and PD-L1—in a complementary manner might be an effective treatment strategy to control advanced thyroid cancers in vivo.

Figure S1. PTCs with BRAFV600E mutations are associated with ICAM-1 Overexpression; Figure S2. Tumor tissue morphology in ATC patients.; Figure S3. ICAM-1-overexpressing ATC cell lines are more proliferative.; Figure S4. ICAM-1 CAR T cell phenotype characterization; Figure S5. Validation of ICAM-1 CAR T cells used in vivo experiments.; Figure S6. Organ weight changes in ATC xenografted mice after ICAM-1 CAR T treatment.; Figure S7. CAR T cells in ICAM-1 CAR T treated and ATC xenografts.; Figure S8. Establishment of ATC patient-derived xenografts.; Figure S9. CAR T activity is detectable throughout the body.; Figure S10. Correlation between ICAM-1 overexpression in TCGA cancer patient tumor tissues and overall survival.

Expression of ICAM1 and PD-L1 in anaplastic thyroid tumor cell lines.

PD1 inhibition enhances survival benefit of CAR T treatment in KHM-5M xenografts.

Purpose: Poorly differentiated thyroid cancer and anaplastic thyroid cancer (ATC) are rare yet lethal malignancies with limited treatment options. Many malignant tumors, including papillary thyroid cancer (PTC) and ATC, are associated with increased expression of ICAM-1, providing a rationale for utilizing ICAM-1–targeting agents for the treatment of aggressive cancer. We developed a third-generation chimeric antigen receptor (CAR) targeting ICAM-1 to leverage adoptive T-cell therapy as a new treatment modality.Experimental Design: ICAM-1 CAR T cells were applied to multiple malignant and nonmalignant target cells to investigate specific target cell death and “off-tumor” toxicity in vitro. In vivo therapeutic efficacy of ICAM-1 CAR T cells was examined in ATC mouse models established from a cell line and patient-derived tumors that rapidly develop systemic metastases.Results: ICAM-1 CAR T cells demonstrated robust and specific killing of PTC and ATC cell lines in vitro. Interestingly, although certain ATC cell lines showed heterogeneous levels of ICAM-1 expression, addition of cytotoxic CAR T cells induced increased ICAM-1 expression such that all cell lines became targetable. In mice with systemic ATC, a single administration of ICAM-1 CAR T cells mediated profound tumor killing that resulted in long-term remission and significantly improved survival. Patient-derived ATC cells overexpressed ICAM-1 and were largely eliminated by autologous ICAM-1 CAR T cells in vitro and in animal models.Conclusions: Our findings are the first demonstration of CAR T therapy against both a metastatic, thyroid cancer cell line and advanced ATC patient-derived tumors that exhibit dramatic therapeutic efficacy and survival benefit in animal studies. Clin Cancer Res; 23(24); 7569–83. ©2017 AACR.

Background Accurate preoperative risk assessment is necessary for informed decision making for patients and surgeons. Several preoperative risk calculators are available but few have been examined in the general thoracic surgical patient population. The Surgical Risk Preoperative Assessment System (SURPAS), a risk-assessment tool applicable to a wide spectrum of surgical procedures, was developed to predict the risks of common adverse postoperative outcomes using a parsimonious set of preoperative input variables. We sought to externally validate the performance of SURPAS for postoperative complications in patients undergoing pulmonary resection. Methods Between January 2016 and December 2018, 2514 patients underwent pulmonary resection at our center. Using data from our institution's prospectively maintained database, we calculated the predicted risks of 12 categories of postoperative outcomes using the latest version of SURPAS. Performance of SURPAS against observed patient outcomes was assessed by discrimination (concordance index) and calibration (calibration curves). Results The discrimination ability of SURPAS was moderate across all outcomes (concordance indices, 0.640 to 0.788). Calibration curves indicated good calibration for all outcomes except infectious and cardiac complications, discharge to a location other than home, and mortality (all overestimated by SURPAS). Conclusions SURPAS demonstrates outcomes for pulmonary resections with reasonable predictive ability. Discretion should be applied when assessing risk for postoperative infectious and cardiac complications, discharge to a location other than home, and mortality. Although the parsimonious nature of SURPAS is one of its strengths, its performance might be improved by including additional factors known to influence outcomes after pulmonary resection, such as sex and pulmonary function.

Background Accurate preoperative risk assessment is critical for informed decision making. The Surgical Risk Preoperative Assessment System (SURPAS) and the National Surgical Quality Improvement Program (NSQIP) Surgical Risk Calculator (SRC) predict risks of common postoperative complications. This study compares observed and predicted outcomes after pulmonary resection between SURPAS and NSQIP SRC. Methods Between January 2016 and December 2018, 2514 patients underwent pulmonary resection and were included. We entered the requisite patient demographics, preoperative risk factors, and procedural details into the online NSQIP SRC and SURPAS formulas. Performance of the prediction models was assessed by discrimination and calibration. Results No statistically significant differences were found between the 2 models in discrimination performance for 30-day mortality, urinary tract infection, readmission, and discharge to a nursing or rehabilitation facility. The ability to discriminate between a patient who will develop a complication and a patient who will not was statistically indistinguishable between NSQIP and SURPAS, except for renal failure. With a C index closer to 1.0, the NSQIP performed significantly better than the SURPAS SRC in discriminating risk of renal failure (C index, 0.798 vs 0.694; P = .003). The calibration curves of predicted and observed risk for each model demonstrate similar performance with a tendency toward overestimation of risk, apart from renal failure. Conclusions Overall, SURPAS and NSQIP SRC performed similarly in predicting outcomes for pulmonary resections in this large, single-center validation study with moderate to good discrimination of outcomes. Notably, SURPAS uses a smaller set of input variables to generate the preoperative risk assessment. The addition of thoracic-specific input variables may improve performance.

Purpose: Advanced thyroid cancers, including poorly differentiated and anaplastic thyroid cancer (ATC), are lethal malignancies with limited treatment options. The majority of patients with ATC have responded poorly to programmed death 1 (PD1) blockade in early clinical trials. There is a need to explore new treatment options. Experimental Design: We examined the expression of PD-L1 (a ligand of PD1) and intercellular adhesion molecule 1 (ICAM1) in thyroid tumors and ATC cell lines, and investigated the PD1 expression level in peripheral T cells of patients with thyroid cancer. Next, we studied the tumor-targeting efficacy and T-cell dynamics of monotherapy and combination treatments of ICAM1-targeting chimeric antigen receptor (CAR) T cells and anti-PD1 antibody in a xenograft model of ATC. Results: Advanced thyroid cancers were associated with increased expression of both ICAM1 and PD-L1 in tumors, and elevated PD1 expression in CD8+ T cells of circulating blood. The expression of ICAM1 and PD-L1 in ATC lines was regulated by the IFNγ–JAK2 signaling pathway. ICAM1-targeted CAR T cells, produced from either healthy donor or patient T cells, in combination with PD1 blockade demonstrated an improved ability to eradicate ICAM1-expressing target tumor cells compared with CAR T treatment alone. PD1 blockade facilitated clearance of PD-L1 high tumor colonies and curtailed excessive CAR T expansion, resulting in rapid tumor clearance and prolonged survival in a mouse model. Conclusions: Targeting two IFNγ-inducible, tumor-associated antigens—ICAM1 and PD-L1—in a complementary manner might be an effective treatment strategy to control advanced thyroid cancers in vivo.

Cancer therapy utilizing adoptive transfer of chimeric antigen receptor (CAR) T cells has demonstrated remarkable clinical outcomes in hematologic malignancies. However, CAR T cell application to solid tumors has had limited success, partly due to the lack of tumor-specific antigens and an immune-suppressive tumor microenvironment. From the tumor tissues of gastric cancer patients, we found that intercellular adhesion molecule 1 (ICAM-1) expression is significantly associated with advanced stage and shorter survival. In this study, we report a proof-of-concept study using ICAM-1-targeting CAR T cells against gastric cancer. The efficacy of ICAM-1 CAR T cells showed a significant correlation with the level of ICAM-1 expression in target cells in vitro. In animal models of human gastric cancer, ICAM-1-targeting CAR T cells potently eliminated tumors that developed in the lungs, while their efficacy was more limited against the tumors in the peritoneum. To augment CAR T cell activity against intraperitoneal tumors, combinations with paclitaxel or CAR activation-dependent interleukin (IL)-12 release were explored and found to significantly increase anti-tumor activity and survival benefit. Collectively, ICAM-1-targeting CAR T cells alone or in combination with chemotherapy represent a promising strategy to treat patients with ICAM-1+ advanced gastric cancer., Graphical Abstract, In this study, we demonstrated the therapeutic potential of CAR T cells targeting ICAM-1 in preclinical models of systemic and intraperitoneal metastases of gastric cancer. A combination with paclitaxel or armoring CAR T cells with inducible IL-12 was found to significantly enhance the treatment effect of CAR T cells.

Risks of thyroidectomy for multinodular goiter (MNG) in older and frail patients are unclear, particularly regarding hematoma and recurrent laryngeal nerve (RLN) palsy. MNG patients undergoing total thyroidectomy were reviewed in the ACS-NSQIP procedure-targeted database (2016–2017). Outcomes were analyzed between adult (age

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 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.

The incidence of papillary thyroid cancer (PTC) in the United States has tripled in the past 30 y. Polybrominated diphenyl ethers (PBDEs) are flame retardants that were ubiquitously used over that time period, and exposure to PBDEs has been associated with PTC prevalence. They are potential carcinogens via their induction of reactive oxygen species (ROS) formation and resultant deoxyribonucleic acid (DNA) damage. We sought to determine the effects of PBDE and tris(2-chloroethyl) phosphate (TCEP), another flame retardant implicated in PTC incidence, on thyrocytes in vitro and measure PBDE levels in human thyroid tissue to determine their carcinogenic potential.Nthy-Ori, an immortalized benign human thyroid follicular cell line was used as a model of normal human thyroid. MTT assays were used to measure cell viability after exposure to PBDEs and TCEP. ROS levels and double-stranded and single-stranded DNA breaks were measured to determine genotoxicity. DNA damage response protein levels were measured with immunoblotting.Exposure to 20μM PBDE or TCEP for 48 h had minimal effects on thyrocyte viability. There was no significant increase in intracellular ROS up to 6 h following PBDE or TCEP exposure in thyrocytes; however, cells exposed to PBDE 47 showed evidence of DNA single-stranded and double-stranded breaks. There was a dose-dependent increase in γH2AX levels following exposure to PBDEs 47 and 209 in Nthy-Ori cells but not with TCEP treatment.PBDE 47 and 209 demonstrated genotoxicity but not cytotoxicity in follicular thyrocytes in vitro. Therefore, PBDE 47 and 209 may be carcinogenic in human thyroid cells.

Laparoscopic adrenalectomy (LA) is the treatment of choice for aldosteronomas and other adrenal tumors. Despite evidence that surgical cure of aldosteronomas is superior to medical treatment, reluctance remains to refer patients for LA. Here we compared the safety profile of LA to laparoscopic cholecystectomy (LC), a commonly performed laparoscopic procedure.Patients undergoing LA or LC from 2012 to 2015 were selected from the National Surgical Quality Improvement Program. Patients who had an LA for an adrenal adenoma or aldosteronoma were compared to those who had LC for biliary colic or cholelithiasis. Multivariable logistic regressions were used to analyze postoperative outcomes between the two groups, controlling for patient factors.A total of 19,315 patients met inclusion criteria (n = 1458 LA, n = 17,857 LC). Patients undergoing an LA were older (median 53 versus 46 y old, P 0.001), with a higher rate of American Society of Anesthesiologists score ≥3 (65.6% versus 25.0%, P 0.001) and modified frailty index score ≥ 1 (78.5% versus 33.6%, P 0.001). Overall mortality was 0.1% with no difference between the two cohorts (P = 0.426). Incidence of at least one postoperative complication was higher in the LA cohort (3.6% versus 2.2%, P 0.001). However, when adjusting for demographics, comorbidities, and operative time, adrenalectomy was not associated with an increased risk of postoperative complications (OR 0.83 (0.6-1.2), P = 0.268).After comparing postoperative outcomes between patients undergoing LA and LC, operation type was not independently associated with an increased incidence of complications. Therefore, physicians should consider LA as having a similar overall risk profile to LC when deciding whether to refer patients to surgery.

Gastroparesis is an end-organ sequela of diabetes. We evaluated the roles of race and socioeconomic status in hospitalization rates and utilization of surgical treatments in these patients. Data was extracted from the National Inpatient Sample (NIS) between the years 2012 and 2014, and any discharge diagnosis of gastroparesis (536.3) was included. Gastrostomy, jejunostomy, and total parenteral nutrition were considered nutritional support procedures, and procedures aimed at improving motility were considered definitive disease-specific procedures: pyloroplasty, endoscopic pyloric dilation, gastric pacemaker placement, and gastrectomy. There were 747,500 hospitalizations reporting a discharge diagnosis of gastroparesis. On multivariable analysis, black race (OR 1.93, 95% CI 1.89–1.98; p

Background: With antiprogrammed death receptor-1 (anti-PD-L1) therapy, a recent meta-analysis reported higher incidence of cutaneous, endocrine and gastrointestinal complications especially with dual anti-PD-L1 immunotherapy (IMM). Methods: Our primary outcome was assessment of all cardiotoxicity grades in IMM compared with different treatments, thus a systemic review and a meta-analysis on randomized clinical trials (RCTs) were done. Results: We included 11 RCTs with 6574 patients (3234 patients in IMM arm vs 3340 patients in the other arm). Three non-small-cell lung cancer RCTs, seven melanoma RCTs and only one prostatic cancer RCT met the inclusion criteria. There were five RCTs that compared monoimmunotherapy to chemotherapy “(n = 2631 patients)”. No difference exists in all cardiotoxicity grades or high-grade cardiotoxicity (p > 0.05). Lung cancer exhibited a higher response rate and lower mortality in IMM. Conclusion: There was no reported statistically significant cardiotoxicity associated with anti-PD/PD-L1 use. Lung cancer subgroups showed better response and survival rates.

Renal transplant allograft function in patients with tertiary hyperparathyroidism who are treated with cinacalcet versus parathyroidectomy remains unclear.This is a retrospective, single-center review of patients with tertiary hyperparathyroidism between 2000 and 2017. We compared clinical parameters and outcomes, including renal allograft failure in patients who had undergone parathyroidectomy versus treatment with cinacalcet therapy.A total of 133 patients were included (33 who received parathyroidectomy and 100 who received cinacalcet); median renal allograft survival was 5.9 years (interquartile range 4.0-9.0). There were no differences in age, sex, body mass index, comorbidities, duration of pretransplant dialysis, cadaveric donor utilization, or rates of delayed allograft function between cohorts. In the parathyroidectomy cohort, normalization of parathyroid hormone occurred more frequently (67% vs 15%, P.001) and renal allograft failure rates were less (9% vs 33%, P = .007), with similar median posttransplant follow-up (7.0 years [interquartile range 4.5-10.0]). On multivariable analysis, parathyroidectomy was inversely associated with allograft failure (odds ratio 0.20, 95%-confidence interval 0.06-0.71, P = .013); there were no other associated factors. A greater median parathyroid hormone (pg/mL) 1 year posttransplant (348 [interquartile range 204-493] vs 195 [interquartile range 147-297], P = .025) was associated with allograft failure in the cinacalcet cohort.Parathyroidectomy for tertiary hyperparathyroidism is associated with lesser rates of renal allograft failure compared with cinacalcet management. Patients with inadequate parathyroid hormone control on cinacalcet at 1 year posttransplant should be considered for parathyroidectomy to prevent potential allograft failure.

Background The Association of Perioperative Registered Nurses (AORN) released new guidelines for operating room attire in 2015 in an attempt to reduce surgical site infections (SSIs). These guidelines have been adopted by the Centers for Medicare and Medicaid Services. We aimed to assess the relationships among operating room attire, SSIs, and healthcare costs. Study Design In March 2016, our center introduced the AORN attire policy. National Health Safety Network data from our hospital were collected on general surgery, cardiac, neurosurgery, orthopaedic, and gynecology procedures from January 2014 to November 2017. The SSI rates and microbiological culture data for 30,493 procedures before and after policy implementation were compared using propensity score matching. The associated costs of the AORN policy were analyzed. Results After 1:1 propensity score matching, 12,585 matched pairs spanning the policy change were included (25,170 patients total); before policy change (BC group) and after policy change (AC group). The rate of SSIs did not differ between groups (1.0% AC group vs 1.1% BC group; p = 0.7). There was no difference in the incidence of Staphylococcal species cultured from wounds (19.3% AC group vs 16.8% BC group; p = 0.6). Multivariable analyses demonstrated that wound classification and emergent procedures were the strongest independent predictors of SSIs. The cost of attire for 1 person entering the operating room increased from $0.07 to $0.12 before policy change to $1.11 to $1.38 after policy change. Use of the mandated operating room long-sleeved jackets alone in our institution was associated with an added cost of $1,128,078 annually, which translates to an estimated $540 million per year for all US hospitals combined. Conclusions Implementation of the AORN guidelines has not decreased SSIs and has increased healthcare costs.

Readmission after coronary artery bypass grafting (CABG) is associated with adverse outcomes and increased cost. We evaluated the impact of a high-value care discharge protocol on readmission, length of stay (LOS), and discharge destination in patients undergoing isolated CABG.In 2016, a comprehensive, patient-centered discharge protocol was implemented. A nurse practitioner was the fulcrum of this program, which focused on improving health literacy, disease management, and rigorous follow-up. All patients undergoing isolated CABG between 2012 and 2019 were retrospectively analyzed with regard to 30-day readmission, LOS, and discharge disposition. Differences were analyzed by Mann-Whitney, chi-square, and t tests. Analyses were repeated using propensity matching.A total of 910 consecutive patients undergoing isolated CABG were included in the analyses: 353 preprotocol and 557 postprotocol. Preprotocol patients had a readmission rate of 14.4% (n = 51), compared with 6.8% (n = 38) in the postprotocol patients (P.001). Median postoperative LOS before implementation was 6 (interquartile range, 5-8) days compared with 5 (interquartile range, 4-6) days postimplementation (P.001). Postimplementation, a higher proportion of patients were discharged to home compared with a skilled nursing facility (82.7% [n = 461] vs 73.9% [n = 261]; P = .002). After propensity matching, 298 well-balanced patients were included for analysis and these significant reductions in LOS, readmission, and discharge destination persisted.Implementation of a new discharge protocol was significantly associated with reduced readmission and LOS, along with higher rates of discharge to home in isolated CABG patients. Importantly, the results were sustainable and did not require additional resources, delivering high-value care.

Objective We sought to evaluate the performance of two commonly used prediction models for postoperative morbidity in patients undergoing open and minimally invasive esophagectomy. Summary background data Patients undergoing esophagectomy have a high risk of postoperative complications. Accurate risk assessment in this cohort is important for informed decision-making. Methods We identified patients who underwent esophagectomy between January 2016 and June 2018 from our prospectively maintained database. Predicted morbidity was calculated using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) Surgical Risk Calculator (SRC) and a 5-factor NSQIP-derived frailty index. Performance was evaluated using concordance index (C-index) and calibration curves. Results In total, 240 consecutive patients were included for analysis. Most patients (85%) underwent Ivor Lewis esophagectomy. The observed overall complication rate was 39%; the observed serious complication rate was 33%. The SRC did not identify risk of complications in the entire cohort (C-index, 0.553), patients undergoing open esophagectomy (C-index, 0.569), or patients undergoing minimally invasive esophagectomy (C-index, 0.542); calibration curves showed general underestimation. Discrimination of the SRC was lowest for reoperation (C-index, 0.533) and highest for discharge to a facility other than home (C-index, 0.728). Similarly, the frailty index had c-index of 0.513 for discriminating any complication, 0.523 for serious complication, and 0.559 for readmission. Conclusions SRC and frailty index did not adequately predict complications after esophagectomy. Procedure-specific risk-assessment tools are needed to guide shared patient-physician decision-making in this high-risk population.

Objectives Follicular variant papillary thyroid carcinoma (FVPTC) is treated similarly to classical variant papillary thyroid carcinoma (cPTC). However, FVPTC has unique tumour features and behaviours. We investigated whether a low dose of radioiodine was as effective as a high dose for remnant ablation in patients with FVPTC and evaluated the recurrence of low-intermediate risk FVPTC. Methods Data from cPTC and FVPTC patients treated with I-131 from 2004 to 2014 were reviewed. Demographics, tumour behaviour, lymph node metastasis, and local recurrence data were compared between FVPTC and cPTC patients. Then, low-intermediate risk FVPTC patients were divided into low, intermediate, and high I-131 dose groups, and postoperative I-131 activities were analysed to evaluate the effectiveness of I-131 therapy for thyroid remnant ablation. Results In total, 799 cases of FVPTC (n = 168) and cPTC (n = 631) treated with I-131 were identified. Patients with FVPTC had a larger primary nodule size than cPTC, but lymph node metastases and local recurrence were more prevalent in cPTC than in FVPTC. For the low-, intermediate-, and high-dose groups, success rates of ablation did not differ (82.0%, 80%, and 81.3%, respectively). Conclusion FVPTC differs from cPTC in behaviour. Low-dose ablation may be sufficient in FVPTC patients with low-intermediate disease risk.

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.

Objective The American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator (NSQIP SRC) was developed to estimate the risk of postoperative morbidity and mortality within 30 days of an operation. We sought to externally evaluate the performance of the NSQIP SRC for patients undergoing pulmonary resection. Methods Patients undergoing pulmonary resection at our center between January 2016 and December 2018 were included. Using data from our institution's prospectively maintained Society of Thoracic Surgeons General Thoracic Database, we identified 2514 patients. We entered requisite patient demographic information, preoperative risk factors, and procedural details into the online calculator. Predicted performance of the calculator versus observed outcomes was assessed by discrimination (concordance index [C-index]) and calibration. Results The observed and predicted probabilities of any complication were 8.3% and 9.9%, respectively, and of serious complications were 7.4% and 9.2%, respectively. Observed and predicted 30-day mortality were 0.5% and 0.9%, respectively. The C-index for readmission was 0.644; the C-indices corresponding to all other outcomes in the NSQIP SRC ranged from 0.703 to 0.821. Calibration curves indicated excellent calibration for all binary end points, with the exception of renal failure (predicted underestimated observed probabilities), discharge to a nursing or rehabilitation facility (overestimated), and sepsis (overestimated). Correlation between predicted and observed length of stay was moderate (Spearman coefficient, 0.562), and calibration was good. Conclusions Except for readmission, renal failure, discharge to a location other than home, and sepsis, the NSQIP SRC can be used to reasonably predict postoperative complications in patients undergoing pulmonary resection.

Background and objectives Hurthle 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 Hurthle 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 Hurthle cell nodules by evaluating differential gene expression in Hurthle cell disease. Methods Eighteen benign Hurthle 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 Hurthle cell nodules. Conclusions CHL1 expression may represent a novel and useful prognostic biomarker to distinguish HCC from benign Hurthle cell disease.

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.

Laparoscopic reoperative anti-reflux surgery (ARS) has a significantly higher morbidity than laparoscopic primary ARS; however, it is not known whether the same pattern exists within the robotic approach. We aimed to evaluate the safety and efficacy of robotic reoperative ARS in comparison with primary robotic ARS. A retrospective review of patients undergoing primary or reoperative robotic ARS at a tertiary referral center between 2012 and 2017 was performed. Perioperative outcomes and long-term symptom resolution were evaluated. A total of 200 patients were included (38 reoperative and 162 primary ARS). Baseline characteristics were comparable across groups. Seven (18.4%) of the reoperative patients had two or more prior foregut operations. Patients in the reoperative group had a longer operative time (226 vs. 180 min, p

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). 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. 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. 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.

Purpose: Poorly differentiated thyroid cancer and anaplastic thyroid cancer (ATC) are rare yet lethal malignancies with limited treatment options. Many malignant tumors, including papillary thyroid cancer (PTC) and ATC, are associated with increased expression of ICAM-1, providing a rationale for utilizing ICAM-1–targeting agents for the treatment of aggressive cancer. We developed a third-generation chimeric antigen receptor (CAR) targeting ICAM-1 to leverage adoptive T-cell therapy as a new treatment modality. Experimental Design: ICAM-1 CAR T cells were applied to multiple malignant and nonmalignant target cells to investigate specific target cell death and “off-tumor” toxicity in vitro. In vivo therapeutic efficacy of ICAM-1 CAR T cells was examined in ATC mouse models established from a cell line and patient-derived tumors that rapidly develop systemic metastases. Results: ICAM-1 CAR T cells demonstrated robust and specific killing of PTC and ATC cell lines in vitro. Interestingly, although certain ATC cell lines showed heterogeneous levels of ICAM-1 expression, addition of cytotoxic CAR T cells induced increased ICAM-1 expression such that all cell lines became targetable. In mice with systemic ATC, a single administration of ICAM-1 CAR T cells mediated profound tumor killing that resulted in long-term remission and significantly improved survival. Patient-derived ATC cells overexpressed ICAM-1 and were largely eliminated by autologous ICAM-1 CAR T cells in vitro and in animal models. Conclusions: Our findings are the first demonstration of CAR T therapy against both a metastatic, thyroid cancer cell line and advanced ATC patient-derived tumors that exhibit dramatic therapeutic efficacy and survival benefit in animal studies. Clin Cancer Res; 23(24); 7569–83. ©2017 AACR.

To determine whether minimally invasive surgery (MIS) training improves outcomes in laparoscopic appendectomy, a procedure that is commonly performed in general surgery training. 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. 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

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.

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...

SUMMARY The positive impact on patient comprehension and improved procedural outcomes when multimedia is utilized to convey instructions preprocedurally has been previously shown for gastrointestinal procedures such as colonoscopy. However, in gastroesophageal reflux testing (GERD), we continue to utilize verbal and written instructions to establish this diagnosis when we use BRAVO pH testing. This is arguably a more complex procedure involving stopping medications, placement of a device, and maintaining an accurate diary for the duration of the testing. We hypothesize that by utilizing multimedia to relay complex textual information, patients will have improved comprehension of periprocedural instructions thereby improving data entry and satisfaction of expectations during the procedure. Prospective randomized study of 120 patients undergoing endoscopic placement of the BRAVO pH monitoring capsule for evaluation of GERD receive either written preoperative instructions (control) or written plus video instructions (video group). A composite comprehension score was calculated using procedure-specific parameters of data entry over the 48-hour monitoring period. Patient satisfaction was evaluated on the basis of a five-point Likert scale. Extent of patient satisfaction was defined by the fulfillment of patient expectations. Exclusion criteria included patients who did not have access to the video or did not complete follow-up. Seventy-eight patients completed all follow-up evaluations. The video group (n = 44) had a significantly higher mean comprehension score when compared to the control group (n = 34) (9.6 ± 1.4 vs. 7.4 ± 2.0, P = 0.01). Overall satisfaction with instructions was significantly higher in the intervention group (91% vs. 47%, p 0.01). We detected no significant difference in comprehension or satisfaction scores in subgroup analyses of the video group comparing patients

Background: Anti-PD/PD-L1-targeted immunotherapy is associated with remarkably high rates of durable clinical responses in patients across a range of tumor types, although their high incidence of skin, gastrointestinal, and endocrine side effects with their use. The risk of pneumonitis associated with checkpoint inhibition therapy is not well described. Methods: A systematic review of the literature was conducted on randomized clinical trials (RCTs) comparing anti-PD/PD-L1 mono-immunotherapy (IMM) to chemotherapy (CTH) protocols in cancer patients. The primary endpoint was the pneumonitis rate in IMM compared to CTH. Secondary endpoints were (I) high-grade pneumonitis rate in IMM compared to CTH and (II) tumor response rate, progression-free survival (PFS), and overall survival (OS) between IMM and CTH. Random model and leave-one-out-analysis were performed. Results: Thirteen RCTs studying 7,246 patients were included; 3,704 (51.12%) patients in the IMM arm and 3,542 (48.88%) patients in the chemotherapy arm. Seven non-small cell lung cancer (NSCLC) RCTs were included with 4,164 patients; 2,101 in the IMM arm and 2,063 patients in the CTH arm. Three RCTs were on melanoma patients (n=1,390). Nine RCTs compared mono-immunotherapy to CTH [docetaxel in 5 studies (38.5%), platinum-based in 2 studies (15.4%), dacarbazine in 1 study (7.7%) and everolimus in 1 study]. Both high-grade and all-grade pneumonitis were higher among patients in the IMM arm when compared to the CTH arm (OR =4.39, 95% CI: 1.65–11.69, P=0.003 and OR =2.46, 95% CI: 1.29–4.6, P=0.007). Tumor response rate was significantly better in the immunotherapy arm (OR =2.31, 95% CI: 1.62–3.29, P

In an attempt to prevent overly aggressive treatment of low-risk thyroid cancers, the American Thyroid Association changed guideline recommendations in late 2015 to state that either hemithyroidectomy or total thyroidectomy are acceptable operations for these patients. We hypothesized that surgeons would increasingly perform hemithyroidectomy after the release of these guidelines.The database of the National Surgery Quality Improvement Program was queried to identify all patients with thyroid cancer who were undergoing thyroidectomy between 2009 and 2017. Patients treated before the release of the 2015 American Thyroid Association guidelines were compared with those treated afterward. Temporal trends in operative rates were assessed quarterly using interrupted time series analyses.A total of 35,291 patients were included in the study. Of those, 26,882 (76.2%) were female and 25,193 (71.3%) were white. After the release of the American Thyroid Association guidelines, there was an increase in hemithyroidectomy rate for patients with cancer from 17.3% to 22.0% (P.001). Interrupted time series analysis controlling for patient factors demonstrated that quarterly growth in the hemithyroidectomy rate accelerated almost 10-fold (P.001) after publication of the revised guidelines. Of note, there was no corresponding increase in the completion thyroidectomy rate (8.3% versus 7.9%, respectively, P = .213). Patients treated with hemithyroidectomy were more likely to be managed as outpatients (70.8% versus 57.1%, P.001), had fewer surgical site infections (0.3% versus 0.5%, P = .050), and had fewer unplanned reintubations (0.2% versus 0.4%, P = .005).In hospitals participating in the National Surgery Quality Improvement Program, the hemithyroidectomy rate increased significantly after the release of the 2015 American Thyroid Association guidelines. Surgeons at hospitals that participate in the National Surgery Quality Improvement Program may be changing practice patterns in response to these guidelines.

IMPORTANCE: Available data comparing the long-term results of hybrid minimally invasive esophagectomy (HMIE) with that of open esophagectomy are conflicting, with similar or even better results reported for the minimally invasive esophagectomy group. OBJECTIVE: To evaluate the long-term, 5-year outcomes of HMIE vs open esophagectomy, including overall survival (OS), disease-free survival (DFS), and pattern of disease recurrence, and the potential risk factors associated with these outcomes. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial is a post hoc follow-up study that analyzes the results of the open-label Multicentre Randomized Controlled Phase III Trial, which enrolled patients from 13 different centers in France and was conducted from October 26, 2009, to April 4, 2012. Eligible patients were 18 to 75 years of age and were diagnosed with resectable cancer of the middle or lower third of the esophagus. After exclusions, patients were randomized to either the HMIE group or the open esophagectomy group. Data analysis was performed on an intention-to-treat basis from November 19, 2019, to December 4, 2020. INTERVENTIONS: Hybrid minimally invasive esophagectomy (laparoscopic gastric mobilization with open right thoracotomy) was compared with open esophagectomy. MAIN OUTCOMES AND MEASURES: The primary end points of this follow-up study were 5-year OS and DFS. The secondary end points were the site of disease recurrence and potential risk factors associated with DFS and OS. RESULTS: A total of 207 patients were randomized, of whom 175 were men (85%), and the median (range) age was 61 (23-78) years. The median follow-up duration was 58.2 (95% CI, 56.5-63.8) months. The 5-year OS was 59% (95% CI, 48%-68%) in the HMIE group and 47% (95% CI, 37%-57%) in the open esophagectomy group (hazard ratio [HR], 0.71; 95% CI, 0.48-1.06). The 5-year DFS was 52% (95% CI, 42%-61%) in the HMIE group vs 44% (95% CI, 34%-53%) in the open esophagectomy group (HR, 0.81; 95% CI, 0.55-1.17). No statistically significant difference in recurrence rate or location was found between groups. In a multivariable analysis, major intraoperative and postoperative complications (HR, 2.21; 95% CI, 1.41-3.45; P

BRAFV600E is the most common driver mutation in anaplastic thyroid cancer, and BRAF inhibitors are increasingly being used in the treatment of this disease. However, the therapeutic benefit of BRAFV600E inhibitors, such as vemurafenib, has been limited in thyroid cancer due to rapid development of drug resistance in clinical practice. Here, we characterize a targetable mechanism of vemurafenib resistance by studying vemurafenib-resistant clones derived from BRAFV600E mutant anaplastic thyroid cancer cell lines (8505C and FRO), and propose a drug combination to overcome resistance. Vemurafenib resistance in these established clones was verified by persistent activation of ERK1/2 after vemurafenib treatment by western blot analysis. RNA-sequencing and subsequent ingenuity pathway analysis (IPA) was used to identify differences in pathway activation after vemurafenib treatment in parental and vemurafenib-resistant cell lines. Treatment of parental cells with vemurafenib resulted in differential gene expression correlating with upstream activation of the IFNγ-STAT1-IRF1 pathway (All FDR < 0.05). Furthermore, parental cells treated with vemurafenib demonstrated higher HLA-II and HLA-A2 expression than untreated cells when analyzed by flow cytometry, implying the activation of IFNγ signaling pathway. In the IPA of a vemurafenib-resistant clone (8505C Res1), IFNγ, STAT1 and IRF1 expression was upregulated compared to their respective untreated parental cell line (All FDR < 0.05). Increased IRF1 expression in 8505C Res1 compared to parental cells was also demonstrated by qPCR, supporting innate IFNγ activation in the resistant clone. Inhibition of the IFNγ pathway with increasing concentrations of neutralizing anti-IFNγ antibody sensitized resistant thyroid cancer cells to vemurafenib. Pharmacologically blocking the IFNγ downstream pathway in resistant clones with AZD1480 (JAK2 inhibitor) or fludarabine (STAT1 inhibitor), resulted in decreased cell viability in combination treatment groups compared to vemurafenib treatment only (cell viability: 92% vemurafenib vs 19% fludarabine combination, p < 0.05) (cell viability: 73% vemurafenib vs 37% AZD1480 combination, p < 0.05). These results demonstrate that activation of the IFNγ pathway is a potential mechanism for the development of resistance of anaplastic thyroid cancer to BRAFV600E inhibitors. Our study suggests that blockade of the IFNγ pathway may potentiate the therapeutic benefit of vemurafenib treatment in this disease. Citation Format: Jessica Limberg, Katherine D. Gray, Mandeep Singh, Timothy M. Ullmann, Brian Wyrwas, Weibin Wang, Zachary Lowenstein, Steve El Eshaky, Heng Liang, Wei Li, Tuo Zhang, Jenny Xiang, Dessislava Stefanova, Rasa Zarnegar, Thomas J. Fahey, Irene M. Min. The role of the IFNγ pathway in the development of vemurafenib resistance in BRAFV600E mutant thyroid carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1895.

The use of the robotic platform has not been well established in patients with super obesity (SO; body mass index, BMI ≥ 50) and super-super obesity (SSO, BMI ≥ 60). We aimed to determine safety and feasibility of robotic bariatric surgery in this cohort. Review of a prospectively maintained database was performed of consecutive patients undergoing robotic bariatric surgery between 2015 and 2017. Propensity score analysis with 1:2 nearest neighbor matching was performed to control for baseline characteristics and procedure type. A propensity-matched cohort of 47 SO patients (median BMI 55.3, range 50.1–92.5) and 94 morbidly obese (MO; median BMI 41.8, range 35.1–48.8) patients were analyzed. After matching, there were no difference in baseline characteristics including age, American Society of Anesthesiologists (ASA) score, or preoperative comorbidities. Most patients in each group underwent sleeve gastrectomy (81% of SO patients versus 76% of MO patients) or Roux-en-Y gastric bypass (13% vs. 18%, respectively), p = 0.66. There were no differences in operative time, intraoperative complications, postoperative complications, or re-admissions between groups. Length of stay was slightly longer in the MO group (2.2 days, IQR 1.8–3.2 vs. 1.8 days, IQR 1.2–2.7; p = 0.01). A subset of SSO patients (n = 11, median BMI 67, range 60–92) was analyzed; there was no increase in operation time, and zero intraoperative complications, conversions to open, or postoperative complications in this subset. Robotic bariatric surgery can safely be performed on patients with SO or SSO with low perioperative morbidity and no increase in operating time.

Objectives We aimed to determine the effect of adjuvant radioactive iodine dose on recurrence rate in high-risk papillary thyroid cancer. Methods More than 1,500 patients treated for papillary thyroid cancer at high-volume centers in France and the United States from 2004–2014 were reviewed. Patients considered at high risk for recurrence per the 2015 American Thyroid Association guidelines were analyzed and grouped by initial radioactive iodine dose: intermediate (median 100 mCi) or high dose (median 150 mCi). Propensity score matching was performed to control for baseline characteristics. Results In a propensity-matched cohort of 66 patient pairs, there were equivalent rates of gross extrathyroidal extension (71% vs 71%, P = 1.00), positive margins (55% vs 55%, P = 1.00), lymph node metastases ≥ 3 cm (9% vs 9%, P = 1.00), extranodal extension (32% vs 33%, P = .85), and distant metastases (2% vs 5%, P = .31). Over a median follow-up of 4.5 years (interquartile ratio 2.0–7.5 years), the intermediate-dose radioactive iodine group had a significantly higher rate of recurrence than patients in the high-dose radioactive iodine group: 24 out of 66 (36%) vs 13 out of 66 (20%), P = .03. Conclusion High-dose radioactive iodine is associated with lower recurrence rate compared with intermediate-dose radioactive iodine for patients with American Thyroid Association high-risk papillary thyroid cancer.