Association of Bethesda category and molecular mutation in patients undergoing thyroidectomy.

OBJECTIVES: The aim of this study was to ascertain the relationship between Bethesda category and molecular mutation of thyroid nodules in patients undergoing thyroidectomy. DESIGN: A retrospective cohort of patients who underwent thyroidectomy following needle biopsy and molecular profile testing was performed. SETTING: Two tertiary care academic hospitals. PARTICIPANTS: Consecutive patients with a dominant thyroid nodule who underwent both USFNA and molecular profile testing followed by thyroidectomy were included in the study. MAIN OUTCOME AND MEASURES: The main outcome was postoperative diagnosis of thyroid cancer and aggressivity of disease based on histopathological variants, nodal metastasis or extra-thyroidal extension. Associations between Bethesda category, molecular mutation and postoperative pathology was assessed using descriptive analysis and chi-square testing. RESULTS: Four hundred fifty-one patients were included. 95.9% (93/97) of patients with a BRAFV600E mutation had a Bethesda category V or VI (p < .001), and all had confirmed thyroid cancer on postoperative pathology. Those with H, K or N RAS or EIF1AX mutations, gene expression profiling (GEP) or copy number alterations showed an association with Bethesda categories III and IV (p ≤ .01). Those with no identified molecular mutation had a lower incidence of aggressive thyroid cancer compared to those with an identified mutation (12.6% vs. 44.3%, p < .01). CONCLUSION: BRAFV600E mutations were associated with thyroid cancer subtypes known to be more aggressive whereas RAS and EIF1AX mutations, copy number alterations, and GEP were related to Bethesda categories III and IV. These findings may help thyroid specialists better identify aggressive thyroid nodules associated with indeterminate Bethesda categories.

Preoperative Risk Index Among Patients Undergoing Thyroid or Parathyroid Surgery.

Importance: Frailty represents a multidimensional syndrome that is increasingly being used to stratify risk in surgical patients. Current frailty risk models are limited among those undergoing thyroid or parathyroid surgery. Objective: To develop and compare preoperative risk indices to determine factors associated with short-term major postoperative adverse events in patients undergoing thyroid or parathyroid surgery. Design, Setting, and Participants: This cohort study evaluated 154 895 patients in the American College of Surgeons National Surgical Quality Improvement Program who underwent thyroid or parathyroid surgery from January 1, 2007, to December 31, 2016. Exposures: Preoperative frailty-related and surgical factors from a derivation cohort were evaluated using simple and multiple logistic regression. Variables potentially associated with postoperative adverse events were subsequently combined into a personalized preoperative Cervical Endocrine Surgery Risk Index (CESRI) and compared with existing risk models using the validation cohort. Main Outcomes and Measures: Composite variable of any major postoperative adverse event, including death, within 30 days of surgery. Results: Of the 154 895 operations reviewed, 3318 patients (2.1%; 2296 women and 1022 men; mean [SD] age, 56.1 [15.6] years) experienced a major postoperative adverse event, with 163 deaths (0.1%). Older age (age, ≥80 years: odds ratio [OR], 2.35; 95% CI, 1.74-3.13), inpatient status (OR, 3.55; 95% CI, 3.08-4.11), male sex (OR, 1.49; 95% CI, 1.29-1.71), current tobacco smoking (OR, 1.25; 95% CI, 1.05-1.48), dyspnea (OR, 1.58; 95% CI, 1.29-1.91), recent weight loss (OR, 1.88; 95% CI, 1.23-2.78), functional dependence (OR, 2.77; 95% CI, 2.05-3.69), obesity (OR, 1.33; 95% CI, 1.10-1.60), anemia (OR, 2.14; 95% CI, 1.82-2.52), leukocytosis (OR, 1.73; 95% CI, 1.38-2.14), hypoalbuminemia (OR, 1.87; 95% CI, 1.56-2.23), use of anticoagulation (OR, 2.16; 95% CI, 1.64-2.81), and length of surgery (>4 hours: OR, 2.92; 95% CI, 2.37-3.59) were independently associated with major adverse events or death on multiple regression analysis (C statistic, 0.77; 95% CI, 0.76-0.78). The area under the curve of the CESRI to determine major adverse events, including death, using the validation cohort was 0.63 (95% CI, 0.61-0.64), with a sensitivity of 0.66 (95% CI, 0.64-0.68) and specificity of 0.66 (95% CI, 0.65-0.66). The CESRI outperformed other risk models for determining adverse events (CESRI vs 5-Factor Modified Frailty Index: delta C index, 0.11; 95% CI, 0.09-0.13; CESRI vs American Society of Anesthesiologists Physical Status Classification System: delta C index, 0.05; 95% CI, 0.03-0.07; CESRI vs American College of Surgeons Risk Calculator: delta C index, 0.02; 95% CI, 0.01-0.03; and CESRI vs Head and Neck Surgery Risk Index: delta C index, 0.04; 95% CI, 0.03-0.06). Conclusions and Relevance: This study suggests that the CESRI is able to determine major postoperative adverse events in patients undergoing thyroid or parathyroid surgery.

Evaluation of a Preoperative Adverse Event Risk Index for Patients Undergoing Head and Neck Cancer Surgery.

Importance: Patients 65 years or older are the most frequent users of operative resources and are also the most vulnerable to postoperative adverse events (AEs). Frailty indices are increasingly being used for preoperative risk stratification within head and neck cancer surgery, but most models lack a multifactorial basis and cannot be directly applied to clinical practice. A practical risk index is needed for clinicians to gauge risk factors preoperatively. Objective: To develop a preoperative risk index of short-term major postoperative AEs for patients undergoing head and neck cancer surgery. Design: Cohort analysis of patients from multiple medical centers undergoing inpatient ablative or reconstructive head and neck cancer surgery and registered in the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) from 2006 to 2016. Exposures: Inpatient ablative or reconstructive head and neck cancer surgery. Main Outcomes and Measures: Sociodemographic, frailty-related, and surgical factors in the derivation cohort were evaluated using simple and multiple logistic regression. Risk factors were subsequently integrated into a preoperative head and neck surgery risk index (HNSRI) and compared with existing models using the validation cohort. A composite variable of major postoperative AEs was used, including death within 30 days of surgery. Results: A total of 43 968 operations were found using the ACS NSQIP database. Of these, 12 569 cases were excluded as non-head and neck cancer or emergency surgery. Of the included 31 399 operations reviewed, the mean (SD) patient age was 56.9 (15.4) years, and 16 994 of the patients were women (54.1%). A total of 4556 (14.5%) patients had a major postoperative AE, and 209 (0.7%) died. Older age, male sex, smoking, anticoagulation, recent weight loss, functional dependence, free-tissue transfer, tracheotomy, duration of surgery, wound classification, anemia, leukocytosis, and hypoalbuminemia were independently associated with major AEs or death on multiple regression analysis (C statistic, 0.83). The area under the curve of the HNSRI to predict major AEs including death using the validation cohort (n = 15 699) was 0.84 (95% CI, 0.83-0.85) with a sensitivity of 80.1% (95% CI, 79.4%-80.8%) and specificity, 72.3% (95% CI, 70.3%-74.2%). The HNSRI outperformed existing risk models for prediction of AEs: delta C index of the HNSRI to the modified frailty index 11, 0.23 (95% CI, 0.22-0.25); the American Society of Anesthesiologists classification, 0.14 (95% CI, 0.13-0.16); and the ACS risk calculator, 0.02 (95% CI, 0.01-0.03). Conclusions and Relevance: The proposed HNSRI demonstrated a high sensitivity and specificity for major postoperative AEs and death in the studied population. This risk index can be used to counsel patients awaiting head and neck cancer surgery.