Faculty Bibliography

BACKGROUND:Secondary hyperparathyroidism (SHPT) affects nearly all patients on maintenance dialysis therapy. SHPT treatment options have considerably evolved over the past 2 decades, but vary in degree of improvement in SHPT. Therefore, we hypothesize that the risks of adverse outcomes after kidney transplantation (KT) may differ by SHPT treatment. METHODS:Using the SRTR and Medicare claims data, we identified 5,094 adults (age≥18) treated with cinacalcet or parathyroidectomy for SHPT prior to receiving KT between 2007-2016. We quantified the association between SHPT treatment and delayed graft function and acute rejection using adjusted logistic models and tertiary hyperparathyroidism (THPT), graft failure, and death using adjusted Cox proportional hazards; we tested whether these associations differed by patient characteristics. RESULTS:Of 5094 KT recipients who were treated for SHPT while on dialysis, 228 (4.5%) underwent parathyroidectomy and 4866 (95.5%) received cinacalcet. There was no association between treatment of SHPT and posttransplant delayed graft function, graft failure or death. However, compared to patients treated with cinacalcet, those treated with parathyroidectomy had a lower risk of developing THPT (aHR=0.56, 95%CI: 0.35-0.89) post-KT. Furthermore, this risk differed by dialysis vintage (pinteraction=0.039). Among patients on maintenance dialysis therapy for ≥3 years prior to KT (n=3,477, 68.3%), the risk of developing THPT was lower when treated with parathyroidectomy (aHR=0.43, 95%CI: 0.24-0.79). CONCLUSIONS:Parathyroidectomy should be considered as treatment for SHPT, especially in KT candidates on maintenance dialysis for ≥3 years. Additionally, patients treated with cinacalcet for SHPT should undergo close surveillance for development of tertiary hyperparathyroidism post-KT.

BACKGROUND:Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy, and many prognostic factors that influence survival remain undefined. Individually, the GRAS (Grade, Resection status, Age, and Symptoms of hormone hypersecretion) parameters have demonstrated their prognostic value in ACC. This study aimed to assess the value of a cumulative GRAS score as a prognostic indicator after ACC resection. METHODS:A retrospective cohort study of adult patients who underwent surgical resection for ACC between 1993 and 2014 was performed using the United States Adrenocortical Carcinoma Group (US-ACCG) database. A sum GRAS score was calculated for each patient by adding one point each when the criteria were met for tumor grade (Weiss criteria ≥ 3 or Ki67 ≥ 20%), resection status (micro- or macroscopically positive margin), age (≥ 50 years), and preoperative symptoms of hormone hypersecretion (present). Overall survival (OS) and disease-free survival (DFS) by cumulative GRAS score were analyzed by the Kaplan-Meier method and log-rank test. RESULTS:Of the 265 patients in the US-ACCG database, 243 (92%) had sufficient data available to calculate a cumulative GRAS score and were included in this analysis. The 265 patients comprised 23 patients (10%) with a GRAS of 0, 52 patients (21%) with a GRAS of 1, 92 patients (38%) with a GRAS of 2, 63 patients (26%) with a GRAS of 3, and 13 patients (5%) with a GRAS of 4. An increasing GRAS score was associated with shortened OS (p < 0.01) and DFS (p < 0.01) after index resection. CONCLUSION/CONCLUSIONS:In this retrospective analysis, the cumulative GRAS score effectively stratified OS and DFS after index resection for ACC. Further prospective analysis is required to validate the cumulative GRAS score as a prognostic indicator for clinical use.

BACKGROUND:Prior studies demonstrated that older adults tend to undergo less surgery for thyroid cancer. Our objective was to use a discrete choice experiment to identify factors influencing surgical decision-making for older adults with thyroid cancer. METHODS:Active and candidate members of the American Association of Endocrine Surgeons were invited to participate in a web-based survey. Multinomial logistic regression was utilized to assess patient and surgeon factors associated with treatment choices. RESULTS:Complete survey response rate was 25.7%. Most respondents were high-volume surgeons (88.5%) at academic centers (76.9%). Multinomial logistic regression demonstrated that patient age was the strongest predictor of management. Increasing age and comorbidities were associated with the choice for active surveillance (P = .000), not performing a lymphadenectomy in patients with nodal metastases (relative-risk ratio: 2.5, 95% CI: 1.4-4.2, P = .002 and relative-risk ratio: 1.6, 95% CI: 1.2-2.1, P = .004, respectively), and recommending hemithyroidectomy versus total thyroidectomy for a cancer >4 cm (relative-risk ratio: 4.4, 95% CI: 2.5-7.9, P = .000 and relative-risk ratio: 3.4, 95% CI: 2.3-5.1, P = .000, respectively). Surgeons with ≥10 years of experience (relative-risk ratio: 3.3, 95% CI: 1.1-10.3, P = .039) favored total thyroidectomy for a cancer <4 cm, and nonfellowship trained surgeons (relative-risk ratio: 7.3, 95% CI: 1.3-42.2, P = .027) opted for thyroidectomy without lymphadenectomy for lateral neck nodal metastases. CONCLUSION:This study highlights the variation in surgical management of older adults with thyroid cancer and demonstrates the influence of patient age, comorbidities, surgeon experience, and fellowship training on management of this population.

BACKGROUND:Current data regarding the risk of malignancy in a large thyroid nodule with benign fine-needle aspiration biopsy(FNAB) is conflicting. We investigated the impact of patient age on the risk of malignancy in nodules≥4 cm with benign cytology. METHODS:We performed a single-institution retrospective review of patients who underwent surgery from 07/2008-08/2019 for a cytologically benign thyroid nodule ≥4 cm. The relationship between malignant histopathology and patient and ultrasound features was assessed with multivariable logistic regression. RESULTS:Of 474 nodules identified, 25(5.3%) were malignant on final pathology. In patients <55 years old, 21/273(7.7%) nodules were malignant, compared to 4/201(2.0%) in patients ≥55. Patient age ≥55 was independently associated with significantly lower risk of malignancy(OR:0.2,95%CI:0.1-0.7,p = 0.011). Increasing nodule size >4 cm and high-risk ultrasound features were not associated with risk of malignancy(OR:1.0,95%CI:0.7-1.4,p = 0.980, and OR:9.6,95%CI:0.9-107.8,p = 0.066, respectively). CONCLUSIONS:Patients <55 years old are 3.7-fold more likely to have a falsely benign FNA biopsy in a nodule≥4 cm.

OBJECTIVE:Clinical practice for differentiated thyroid cancer is moving towards lobectomy rather than total thyroidectomy in patients at low risk of recurrence. However, recurrence risk assessment depends on post-operative findings, while the surgical decision is based on preoperative factors. We determined the preoperative predictors of occult higher-risk pathology and rates of completion thyroidectomy among surgical candidates with nonbenign thyroid nodules 10 to 40 mm and no evidence of extrathyroidal extension or metastasis on preoperative evaluation. METHODS:Thyroid surgery cases at a single institution from 2005-2015 were reviewed to identify those meeting American Thyroid Association (ATA) criteria for lobectomy. ATA-based risk stratification from postoperative surgical pathology was compared to preoperative cytopathology, ultrasound, and clinical findings. RESULTS:Of 1,995 thyroid surgeries performed for nonbenign thyroid nodules 10 to 40 mm, 349 met ATA criteria for lobectomy. Occult high-risk features such as tall cell variant, gross extrathyroidal invasion, or vascular invasion were found in 36 cases (10.7%), while intraoperative lymphadenopathy led to surgical upstaging in 13 (3.7%). Intermediate risk features such as moderate lymphadenopathy or minimal extrathyroidal extension were present in an additional 44 cases. Occult risk features were present twice as often in Bethesda class 6 cases (35%) as in lower categories (12 to 17%). In multivariable analysis, Bethesda class and nodule size, but not age, race, sex, or ultrasound features, were significant predictors of occult higher-risk pathology. CONCLUSION/CONCLUSIONS:Most solitary thyroid nodules less than 4 cm and with cytology findings including atypia of undetermined significance through suspicious for papillary thyroid cancer would be sufficiently treated by lobectomy. ABBREVIATIONS/BACKGROUND:ATA = American Thyroid Association; CND = central neck dissection; DTC = differentiated thyroid cancer; ETE = extrathyroidal extension; FNA = fine needle aspiration; FTC/HCC = follicular thyroid carcinoma/Hurthle cell carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; OR = odds ratio; PTC = papillary thyroid cancer; US = ultrasound.

BACKGROUND:Adrenocortical carcinoma is a rare, aggressive cancer. We compared features of patients who underwent synchronous versus metachronous metastasectomy. METHODS:Adult patients who underwent resection for metastatic adrenocortical carcinoma from 1993 to 2014 at 13 institutions of the US adrenocortical carcinoma group were analyzed retrospectively. Patients were categorized as synchronous if they underwent metastasectomy at the index adrenalectomy or metachronous if they underwent resection after recurrence of the disease. Factors associated with overall survival were assessed by univariate analysis. RESULTS:In the study, 84 patients with adrenocortical carcinoma underwent metastasectomy; 26 (31%) were synchronous and 58 (69%) were metachronous. Demographics were similar between groups. The synchronous group had more T4 tumors at the index resection (42 vs 3%, P < .001). The metachronous group had prolonged median survival after the index resection (86.3 vs 17.3 months, P < .001) and metastasectomy (36.9 vs 17.3 months, P = .007). Synchronous patients with R0 resections had improved survival compared to patients with R1/2 resections (P = .008). Margin status at metachronous metastasectomy was not associated with survival (P = .452). CONCLUSION/CONCLUSIONS:Select patients with metastatic adrenocortical carcinoma may benefit from metastasectomy. Patients with metachronous metastasectomy have a more durable survival benefit than those undergoing synchronous metastasectomy. This study highlights need for future studies examining differences in tumor biology that could explain outcome disparities in these distinct patient populations.

Increased hormonal secretion of aldosterone, cortisol, or catecholamines from an adrenal gland can produce a variety of undesirable symptoms, including hypertension, which may be the initial presenting symptom. Consequences of secondary hypertension can result in potential cardiovascular and cerebrovascular complications at higher rates than in those with essential hypertension. Once a biochemical diagnosis is confirmed, targeted pharmacotherapy can be initiated to improve hypertension and may be corrected with surgical intervention. Adrenalectomy can be curative and can reverse the risk of cardiovascular sequelae once blood pressure control is achieved. This article discusses perioperative and operative considerations of adrenal causes of hypertension.

OBJECTIVES:Despite intact recurrent laryngeal nerves, patient-reported voice and swallowing changes are common after thyroidectomy. The association between patient age or frailty status and these changes is unknown. The aim of this study was to evaluate the impact of age and frailty on the incidence of voice and swallowing alterations after thyroidectomy. METHODS:We performed an institutional review board (IRB)-approved retrospective review of consecutive patients who underwent total thyroidectomy with intraoperative recurrent laryngeal nerve (RLN) monitoring at a single institution between January 2014 and September 2016. Patients with RLN injury were excluded. After data extraction, a modified frailty index (mFI) was calculated for each patient. The association among risk factors, including age, mFI, prior history of neck surgery, frequent voice use, presence of malignancy or gastroesophageal reflux disease, and smoking status and reported voice and/or swallowing changes was examined. RESULTS:Of 924 patients undergoing thyroidectomy, 148 (16.0%) reported only changes in voice; 52 (5.6%) reported only difficulty in swallowing; and 26 (2.8%) reported changes with both voice and swallowing. On multivariate analysis, we found a significant increase in voice or swallowing alterations up to the age of 50 years (5% increased odds per year), after which these changes plateaued. We found that mFI was not associated with voice or swallowing changes. CONCLUSION:Age ≥ 50 years is independently associated with the development of voice or swallowing changes after thyroidectomy, despite intact RLN. Additional prospective studies are needed to validate these findings, further define this association, and identify risk factors for developing these changes. LEVEL OF EVIDENCE:2b Laryngoscope, 129:519-524, 2019.

Adrenalectomy is the standard of care for management of many adrenal tumor types and, in the United States alone, approximately 6000 adrenal surgeries are performed annually. Two general approaches to adrenalectomy have been described; (1) the open approach, in which a diseased adrenal is removed through a large (10-20 cm) abdominal wall incision, and (2) the minimally invasive approach, in which laparoscopy is used to excise the gland through incisions generally no longer than 1-2 cm. Given these disparate technique options, clear preoperative characterization of those specific disease features that inform selection of adrenalectomy approach is critically important to the surgeon. Because most of these features are directly assessed via preoperative abdominal imaging, in particular computed tomography (CT) scanning, a clear mutual understanding among surgeons and radiologists of those adrenal tumor features impacting operative approach selection is vital for planning adrenal surgery. In this context, we review the preoperative CT imaging features that specifically inform adrenalectomy approach selection, provide illustrative examples from our institution's imaging and surgical archives, and provide a stepwise guide to both the open and laparoscopic adrenalectomy approaches.