Don't chase the adenoma: A probabilistic approach to imaging before parathyroidectomy.

BACKGROUND: Preoperative imaging before parathyroidectomy can localize adenomas and reduce unnecessary bilateral neck explorations. We hypothesized that (1) the utility of preoperative imaging varies substantially depending on the preoperative probability of having adenoma(s) and (2) that a selective imaging approach based on this probability could avoid unnecessary patient costs and radiation. METHODS: We analyzed 3,577 patients who underwent parathyroidectomy for primary hyperparathyroidism from 2001 to 2022. The predicted probability of patients having single or double adenoma versus hyperplasia was estimated using logistic regression. We then estimated the relationship between the predicted probability of single/double adenoma and the likelihood that sestamibi or 4-dimensional computed tomography was helpful for operative planning. Current Medicare costs and published data on radiation dosing were used to calculate costs and radiation exposure from non-helpful imaging. RESULTS: The mean age was 62 ± 13 years; 78% were women. Adenomas were associated with higher mean calcium (11.2 ± 0.74 mg/dL) and parathyroid hormone levels (140.6 ± 94 pg/mL) than hyperplasia (9.8 ± 0.52 mg/dL and 81.4 ± 66 pg/mL). The probability that imaging helped with operative planning increased from 12% to 65%, as the predicted probability of adenoma increased from 30% to 90%. For every 10,000 patients, a selective approach to imaging that considered the preoperative probability of having adenomas could save patients up to $3.4 million and >239,000 millisieverts of radiation. CONCLUSION: Rather than imaging all patients with primary hyperparathyroidism, a selective strategy that considers the probability of having adenomas could reduce costs and avoid excess radiation exposure.

Validated predictive model for treatment and prognosis of adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma has a poor prognosis and multiple clinical, pathological, and treatment variables. Currently, we lack a prognostic and treatment calculator to determine the survival and efficacy of adjuvant chemoradiation. We aimed to validate a calculator to assess prognosis and treatment. METHODS: We searched the National Cancer Database to identify patients with adrenocortical carcinoma surgically treated from 2004 to 2020 and randomly allocated them into a training (80%) or validation set (20%). We analyzed the variables of age; sex; Charlson Comorbidity Index; insurance status; tumor size; pathologic tumor, node, and metastasis categories; surgical margins; and use of chemotherapy and radiation therapy. We used Cox regression prediction models and bootstrap coefficients to generate a mathematical model to predict 5- and 10-year overall survival. After using the area under the curve analysis to assess the model's performance, we compared overall survival in the training and validation sets. RESULTS: Multivariable analysis of the 3,480 patients included in the study revealed that all variables were significant except sex (P < .05) and incorporated into a mathematical model. The area under the curve for 5- and 10-year overall survival was 0.68 and 0.70, respectively, for the training set and 0.70 and 0.72, respectively, for the validation set. For the bootstrap coefficients, the 5- and 10-year overall survival was 6.4% and 4.1%, respectively, above the observed mean. CONCLUSION: Our model predicts the overall survival of patients with adrenocortical carcinoma based on clinical, pathologic, and treatment variables and can assist in individualizing treatment.

Lymph node imaging for thyroid cancer.

Cervical lymph nodes (LNs) in the central (level VI) and lateral (levels II-V) compartments of the neck are the most common sites of locoregional metastases associated with thyroid cancer. Prophylactic nodal dissections are uncommon in modern thyroid surgery and are not routinely performed due to concern for increased morbidity and do not offer improved survival. Therefore, a selective approach for LN dissections is increasingly important. Preoperatively, this is most frequently assessed with cervical ultrasound (US). Contrast-enhanced computed tomography (CT) of the neck can also be used for preoperative assessment. Both US and CT imaging can be used to characterise LNs in levels II-VI and their risk of malignancy based on size, morphology, and growth. US-guided fine-needle aspiration of equivocal LN with thyroglobulin (Tg) washout can also determine if a LN harbours malignancy. For postoperative surveillance after total thyroidectomy, both US and CT continue to play an important role at 6-12 months intervals. These patients may also benefit from additional biochemical data such as Tg levels in addition to LN and thyroid bed imaging. Thyroid uptake scans may also play a role in LN surveillance postoperatively for well-differentiated thyroid carcinoma in certain clinical contexts. Less commonly, positron emitted tomography may play a role, but is typically reserved for patients with aggressive or radioactive iodine refractory disease.

Treatment Differences for Adrenocortical Carcinoma by Race and Insurance Status.

INTRODUCTION: To determine if treatment and clinical outcomes of adrenocortical carcinoma (ACC) vary by race and insurance status. METHODS: ACC patients from the National Cancer Database (2004-2017) were reviewed. Race was defined as White versus minority (Black and Hispanic). Insurance types were private (PI) versus other (Medicaid/uninsured/unknown). Metastatic ACC (M-ACC) was defined as distant metastases at the time of diagnosis; nonmetastatic ACC (NM-ACC) patient had no distant disease. RESULTS: Of 2351 NM-ACC patients, 83.6% were White and 16.4% minority. There were 1216 M-ACC patients, with 80.3% White and 19.8% minority. Both White NM-ACC and M-ACC patients had more PI (each P < 0.001). PI NM-ACC was associated with a shorter duration from diagnosis to first treatment (14 versus 18 d, P = 0.005). Both NM-ACC and M-ACC with PI were more likely to receive surgery (92.6% versus 86.9%, P = 0.001 and 35.4% versus 27%, P = 0.02) and to receive surgery sooner (13 versus 16 d, P = 0.03). M-ACC with PI were more likely to receive chemotherapy (63.6% versus 54.3%, P = 0.01) and to have lymph nodes examined (14.8% versus 8.6%, P = 0.02). Length of stay postoperatively was shorter for White NM-ACC (6 versus 7 d, P = 0.04) and M-ACC (8 versus 17 d, P = 0.02). For NM-ACC and M-ACC, the 30-d readmission, 90-d mortality, and overall survival were similar by race. A multivariable analysis showed minorities (OR 0.69, 95% confidence interval 0.54-0.88, P = 0.003) and patients without PI (OR 0.75, 95% confidence interval 0.58-0.97, P = 0.03) were less likely to have surgery. However, a multivariable analysis showed survival was similar for White versus minority patients and PI versus other. CONCLUSIONS: White NM-ACC or M-ACC and PI were more likely to receive surgery and timely multimodality care. These disparities were not associated with differences in 90-d mortality or overall survival.

Treatment differences at high volume centers and low volume centers in non-metastatic and metastatic adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is rare with poor survival. Do treatment and outcomes vary by volume? METHODS: NCDB (2004-2017) was searched for patients with ACC. High-volume centers (HVCs) were defined by ≥ 15 ACC and low-volume centers by ≤ 7 total cases. Multivariable Cox and logistic regression analysis were performed. RESULTS: ACC patients at HVCs were significantly more likely to have surgery, chemotherapy, and had lower 90-day readmission. HVCs were significantly more likely than LVCs to administer chemotherapy to surgical NonMetastatic (NM)-ACC patients. There was no significant difference in overall survival (OS), 90-day mortality, length of stay, or radiation treatments between the two. Operative Metastatic (M)-ACC at HVC had significantly improved OS, more chemotherapy administered, and lower 90-day mortality. CONCLUSION: NM-ACC and M-ACC treated at HVCs were more likely to have surgery and multimodality therapy. NM-ACC having surgery at HVCs and LVCs had similar OS. M-ACC at HVCs had improved OS and 90-day mortality.

Radioactive iodine does not improve overall survival for patients with aggressive variants of papillary thyroid carcinoma less than 2 cm.

BACKGROUND: Tall cell and diffuse sclerosing variants of papillary thyroid cancer are associated with aggressive features. Radioactive iodine after total thyroidectomy is poorly studied. METHODS: Patients ≥18 years in the National Cancer Data Base from 2004 to 2016 with classic papillary thyroid cancer, tall cell, or diffuse sclerosing 1 mm to 40 mm were identified. Logistic regression identified factors associated with aggressive features. Overall survival was assessed using Kaplan-Meier method and log-rank tests, after propensity score matching for clinicopathological and treatment variables. RESULTS: A total of 155,940 classic papillary thyroid cancer patients, 4,011 tall cell, and 507 diffuse sclerosing were identified. Tall cell patients represented an increasing proportion of the study population during the analysis period, whereas diffuse sclerosing and classic papillary thyroid cancer patients showed a statistically significant decline. Extrathyroidal extension and nodal involvement were more prevalent among tall cell and diffuse sclerosing patients when compared to those diagnosed with classic papillary thyroid cancer (P < .01). Adjuvant radioactive iodine was less frequently used in patients with classic papillary thyroid cancer when compared to tall cell and diffuse sclerosing patients (42.6% vs 62.4%, 59.0%; P < .001, respectively). Aggressive variants receiving total thyroidectomy versus total thyroidectomy + radioactive iodine propensity score matched across clinicopathologic variables were analyzed. There was no difference in overall survival between the 2 treatment groups for tumors <2 cm (01-1.0 cm, 92.2% vs 84.8%; P = .98); (1.0-2.0 cm, 72.7% vs 88.1%; P = .82). However, overall survival was improved for total thyroidectomy + radioactive iodine propensity score matched patients with tumor sizes 21 to 40 mm versus total thyroidectomy (83.4% vs 70.0%, P = .004). CONCLUSION: For aggressive tumor variants ≤2 cm treated with total thyroidectomy, there is no overall survival advantage provided by the addition of adjuvant radioactive iodine.

Overall survival is improved with total thyroidectomy and radiation for male patients and patients older than 55 with T2N0M0 Stage 1 classic papillary thyroid cancer.

BACKGROUND: We examine whether surgery extent and radiation administration affect overall survival for cT2N0M0 classic papillary thyroid cancer according to age and sex. METHODS: Patients with cT2N0M0 classic papillary thyroid cancer tumors in the National Cancer Data Base (2004-2016) were selected. Multivariable Cox regression analysis compared patients (combined male + female cohorts) having lobectomy to those having total thyroidectomy with or without radiation (primarily radioactive iodine) for ages: 18 to 45, 46 to 55, and >55 years. In addition, 1:1 propensity score matching and Kaplan-Meier curves with 10-year overall survival estimates, and log-rank test were stratified by age and sex. RESULTS: Lobectomy had equivalent overall survival to total thyroidectomy without and with radiation for patients (combined male + female cohorts) aged 18 to 45 and 46 to 55 years on multivariable analysis. On propensity score matching there was overall survival advantage for total thyroidectomy with radiation over both lobectomy and total thyroidectomy for men (ages 18-90+ combined) and overall survival advantage in patients (combined male + female cohort) aged >55 years having total thyroidectomy with radiation versus lobectomy. On propensity score matching there were no overall survival differences in women (ages 18-90+ combined) or patients (combined male + female cohort) aged 18 to 45 and 46 to 55 years having either lobectomy, total thyroidectomy, or total thyroidectomy with radiation. CONCLUSION: For cT2N0M0 classic papillary thyroid cancer, total thyroidectomy with radiation improves 10-year overall survival for patients (combined male + female cohort) aged >55 years and men (ages 18-90+ combined).

Racial Disparities of Adrenalectomy.

PURPOSE: Racial disparities of surgical outcomes have been demonstrated for a variety of operations. We sought to determine whether minority status is associated with disparate care for adrenalectomy. METHODS: This study is a retrospective database review of the Collaborative Endocrine Surgery Quality Improvement Program (CESQIP) from January 1, 2014 through April 30, 2018. Primary outcome was complication rate. Secondary outcomes were length of stay and surgeon experience. Minority status was defined as Black or Hispanic and outcomes were compared with White patients. RESULTS: For the study period, 1141 patients who underwent adrenalectomies were included, of whom 69.9% were White and 22.6% minority. The minority patients were significantly younger with higher rates of diabetes mellitus. Minority patients had higher rates of complication and longer length of stay. Minority patients were more likely to have an adrenalectomy by a low-volume surgeon. In multivariate logistic regression, minority status remained associated with complication rate. CONCLUSIONS: Minority patients undergoing adrenalectomy have higher rates of complication and longer lengths of stay when controlling for common comorbidities. Minority patients have decreased access to high-volume surgeons.

Trends in nonoperative management of papillary thyroid microcarcinoma.

BACKGROUND: In 2010, a Japanese trial of nonoperative management for papillary thyroid microcarcinomas (PTmC) was published. This study determines if the prevalence of nonoperative management in the United States has changed and if there are predictors of this approach. METHODS: Patients treated for PTmC between 2004 and 2015 in the National Cancer Data Base were identified. Inclusion criteria were: classic or follicular variant papillary cancer histology, tumor size 1 to 10 mm, cN0 disease and no extrathyroidal extension or metastatic disease. Nonoperative management was assessed over time and compared between 2004-2010 and 2010-2015. Logistic regression identified factors associated with nonoperative management. RESULTS: Of 65 381 PTmC patients, 344 (0.5%) were treated nonoperatively. The annual rate of nonoperative management was similar at 0.6% in 2004 to 0.4% in 2010 (P = .755) but increased to 0.9% in 2015 (P < .001). There was no difference in patient age, race, comorbidities, or reason for nonoperative management between the two periods. Academic centers managed more patients nonoperatively. Multivariable logistic regression suggests older age, facility type, location, Hispanic, Asian, and Native American ethnicity were associated with nonoperative management. CONCLUSION: The vast majority of PTmC in the United States is treated with an operation. A small but significant increase in nonoperative management occurred between 2004-2010 and 2010-2015.

Aggressive variants of papillary thyroid microcarcinoma are associated with high-risk features, but not decreased survival.

BACKGROUND: This study compares pathologic features and overall survival of classic versus aggressive variants of papillary thyroid microcarcinoma (PMTC). METHODS: Patients ≥18 years in the National Cancer Data Base (2004-2015) with the subtypes of classic (cPTMC), tall cell (mTCV), or diffuse sclerosing (mDSV) PTC (≤1 cm) were identified. Overall survival was analyzed by Kaplan-Meier and propensity matched for clinicopathologic and treatment variables. RESULTS: There were 82,056 cPTMC patients, 923 mTCV, and 219 mDSV. Extrathyroidal extension and nodal involvement were more frequent in mTCV and mDSV versus cPTMC (P < .01). mTCV had more distant metastases than cPTMC (P = .02). On multivariable analysis, mTCV (odds ratio 4.19 [3.58-4.92], P < .001) and mDSV (odds ratio 2.76 [1.92-3.97]; P < .01) histologies were predictors of extrathyroidal extension. mTCV was an independent predictor of nodal metastases (odds ratio 1.51 [1.25-1.83], P < .01). Total thyroidectomy and radioactive iodine treatment were more commonly used in mTCV and mDSV patients when compared with cPTMC patients. Despite more aggressive features and more aggressive treatment in mTCV and mDSV patients, there was no difference in overall survival when compared with propensity-matched cPTMC patients. CONCLUSION: Although mTCV and mDSV have more aggressive pathologic features and were treated more aggressively, there were no differences in overall survival compared with propensity-matched cPTMC patients.

Survival with Follicular and Hurthle Cell Microcarcinoma Compared to Papillary Thyroid Microcarcinoma: A Population Study of 84,532 Patients.

BACKGROUND: This study compares survival in patients with the rare subtypes of follicular (FTmC) and Hurthle cell (HCmC) microcarcinoma compared to that of papillary thyroid (PTmC) microcarcinoma. METHODS: Patients with FTmC and HCmC were selected from the National Cancer Database 2004-2015 and compared with PTmC. Patient clinicopathological characteristics and overall survival (OS) were analyzed. Multivariable logistic and Cox regression analysis evaluated binary outcomes and predictors of survival. A propensity score matched analysis using age, gender, race, extrathyroidal extension (ETE), nodal status, distant metastasis, radiation, and operation was performed to evaluate the difference in OS with FTmC, HCmC, and PTmC. RESULTS: We identified 858 FTmC, 476 HCmC, and 82,056 PTmC. FTmC was less likely to have macroscopic ETE compared to PTmC (2.6% vs. 3.1% p = 0.03), but more likely to have distant metastasis (2.3% vs. 0.2%, p < 0.01). FTmC and HCmC were less likely to have nodal metastasis (2.7%, 2.5% vs. 10.9%, p < 0.01). Ten-year OS was decreased in patients with FTmC (91.4%, p = 0.04) and HCmC (89.8%, p < 0.01) compared to PTmC (93.5%). On multivariable analysis, histology was not associated with OS. With HCmC, older age (OR 1.13, p < 0.01) and male gender (OR 2.72, p = 0.03) were associated with decreased OS. In propensity matched analysis, there was no difference in 10-year OS with FTmC and PTmC (91.4% vs. 93.7%, p = 0.54), but HCmC had decreased OS compared to PTmC (89.8% vs. 94.3%, p = 0.04). CONCLUSIONS: Patients with FTmC have comparable OS to those with PTmC, but HCmC has decreased OS especially in older and male patients.