Incidental 68Ga-DOTATATE uptake in thyroid nodules: Is guideline-directed management still appropriate?

BACKGROUND: Fluorodeoxyglucose uptake on positron emission tomography imaging has been shown to be an independent risk factor for malignancy in thyroid nodules. More recently, a new positron emission tomography radiotracer-Gallium-68 DOTATATE-has gained popularity as a sensitive method to detect neuroendocrine tumors. With greater availability of this imaging, incidental Gallium-68 DOTATATE uptake in the thyroid gland has increased. It is unclear whether current guideline-directed management of thyroid nodules remains appropriate in those that are Gallium-68 DOTATATE avid. METHODS: We retrospectively reviewed Gallium-68 DOTATATE positron emission tomography scans performed at our institution from 2012 to 2022. Patients with incidental focal Gallium-68 DOTATATE uptake in the thyroid gland were included. Fine needle aspiration biopsies were characterized via the Bethesda System for Reporting Thyroid Cytopathology. Bethesda III/IV nodules underwent molecular testing (ThyroSeq v3), and malignancy risk ≥50% was considered positive. RESULTS: In total, 1,176 Gallium-68 DOTATATE PET scans were reviewed across 837 unique patients. Fifty-three (6.3%) patients demonstrated focal Gallium-68 DOTATATE thyroid uptake. Nine patients were imaged for known medullary thyroid cancer. Forty-four patients had incidental radiotracer uptake in the thyroid and were included in our study. Patients included in the study were predominantly female sex (75%), with an average age of 62.9 ± 13.9 years and a maximum standardized uptake value in the thyroid of 7.3 ± 5.3. Frequent indications for imaging included neuroendocrine tumors of the small bowel (n = 17), lung (n = 8), and pancreas (n = 7). Thirty-three patients underwent subsequent thyroid ultrasound. Sonographic findings warranted biopsy in 24 patients, of which 3 were lost to follow-up. Cytopathology and molecular testing results are as follows: 12 Bethesda II (57.1%), 6 Bethesda III/ThyroSeq-negative (28.6%), 1 Bethesda III/ThyroSeq-positive (4.8%), 2 Bethesda V/VI (9.5%). Four nodules were resected, revealing 2 papillary thyroid cancers, 1 neoplasm with papillary-like nuclear features, and 1 follicular adenoma. There was no difference in maximum standardized uptake value between benign and malignant nodules (7.0 ± 4.6 vs 13.1 ± 5.7, P = .106). Overall, the malignancy rate among patients with sonography and appropriate follow-up was 6.7% (2/30). Among patients with cyto- or histopathology, the malignancy rate was 9.5% (2/21). There were no incidental cases of medullary thyroid cancer. CONCLUSION: The malignancy rate among thyroid nodules with incidental Gallium-68 DOTATATE uptake is comparable to rates reported among thyroid nodules in the general population. Guideline-directed management of thyroid nodules remains appropriate in those with incidental Gallium-68 DOTATATE uptake.

The impact of patient age on practice patterns and outcomes for primary hyperparathyroidism.

BACKGROUND: Management of asymptomatic primary hyperparathyroidism (PHPT) in older patients (age >50) is controversial. The 4th International Workshop on the Management of Asymptomatic PHPT recommends surveillance for older patients who lack objective signs of disease, whereas The American Association of Endocrine Surgeons (AAES) guidelines recommend consideration of parathyroidectomy for patients of any age with subjective constitutional, neuropsychiatric, or cognitive symptoms. Therefore, the primary objective of this study was to evaluate the association between patient age and both practice patterns and outcomes in the management of patients with sporadic PHPT. METHODS: The Collaborative Endocrine Surgery Quality Improvement Program (CESQIP) database was queried for all adults (age ≥18) who underwent an index parathyroidectomy for sporadic primary hyperparathyroidism between 2014 and 2020. Associations between patient age (≤50 years vs. >50 years) and both practice patterns and outcomes were evaluated separately using adjusted multivariable logistic and multinomial regression models. RESULTS: Of 9,938 patients who underwent parathyroidectomy, 8,080 (81.3%) were >50 years old and 1,858 (18.7%) were ≤50. Of this cohort, 17% of older patients and 26% of younger patients presented with only subjective symptoms. Compared to younger patients, older patients were more likely to have an objective indication for parathyroidectomy (aOR = 1.8, 95%CI: 1.6-2.0, p < 0.001). They were also more likely to undergo ≥2 imaging studies pre-operatively (aOR = 1.2, 95%CI: 1.1-1.3, p = 0.003), to undergo bilateral neck exploration (aOR = 1.4, 95%CI: 1.3-1.6, p < 0.001), and to have multi-gland disease (aOR = 1.6, 95%CI: 1.4-1.8, p < 0.001). There was no difference between age groups and parathyroidectomy-related complications including hypocalcemia, vocal cord dysfunction, hematoma requiring evacuation, or reintubation, however, older patients were less likely to have any peri-operative morbidity (aOR = 0.7, 95%CI: 0.6-0.9, p = 0.011). CONCLUSIONS: Older patients were more likely to meet objective criteria prior to undergoing parathyroidectomy by CESQIP participating high-volume endocrine surgeons, however they were less likely to have peri-operative complications compared to younger patients. Given the growing evidence demonstrating improvement of both objective and subjective symptoms after parathyroidectomy for PHPT, additional studies are still needed to fully understand the benefit of surgical referral in older adults for less objective indications.

Prevalence and risk factors for tertiary hyperparathyroidism in kidney transplant recipients.

BACKGROUND: Tertiary hyperparathyroidism after kidney transplantation has been associated with graft dysfunction, cardiovascular morbidity, and osteopenia; however, its true prevalence is unclear. The objective of our study was to evaluate the prevalence of and risk factors for tertiary hyperparathyroidism. METHODS: A prospective cohort of 849 adult kidney transplantation recipients (December 2008-February 2020) was used to estimate the prevalence of hyperparathyroidism 1-year post-kidney transplant. Tertiary hyperparathyroidism was defined as hypercalcemia (≥10mg/dL) and hyperparathyroidism (parathyroid hormone≥70pg/mL) 1-year post-kidney transplantation. Modified Poisson regression models were used to evaluate risk factors associated with the development of both persistent hyperparathyroidism and tertiary hyperparathyroidism. RESULTS: Among kidney transplantation recipients, 524 (61.7%) had persistent hyperparathyroidism and 182 (21.5%) had tertiary hyperparathyroidism at 1-year post-kidney transplantation. Calcimimetic use before kidney transplantation was associated with 1.30-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.30, 95% CI: 1.12-1.51) and 1.84-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 1.84, 95% CI: 1.25-2.72). Pre-kidney transplantation parathyroid hormone ≥300 pg/mL was associated with 1.49-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.49, 95% CI = 1.19-1.85) and 2.21-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 2.21, 95% CI = 1.25-3.90). Pre-kidney transplantation tertiary hyperparathyroidism was associated with an increased risk of post-kidney transplantation tertiary hyperparathyroidism (adjusted prevalence ratio = 1.71, 95% CI = 1.29-2.27), but not persistent hyperparathyroidism. Furthermore, 73.0% of patients with persistent hyperparathyroidism and 61.5% with tertiary hyperparathyroidism did not receive any treatment at 1-year post-kidney transplantation. CONCLUSION: Persistent hyperparathyroidism affected 61.7% and tertiary hyperparathyroidism affected 21.5% of kidney transplantation recipients; however, the majority of patients were not treated. Pre-kidney transplantation parathyroid hormone levels ≥300pg/mL and the use of calcimimetics are associated with the development of tertiary hyperparathyroidism. These findings encourage the re-evaluation of recommended pre-kidney transplantation parathyroid hormone thresholds and reconsideration of pre-kidney transplantation secondary hyperparathyroidism treatments to avoid the adverse sequelae of tertiary hyperparathyroidism in kidney transplantation recipients.

Association Between Treatment of Secondary Hyperparathyroidism and Posttransplant Outcomes.

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 Scientific Registry of Transplant Recipients and Medicare claims data, we identified 5094 adults (age ≥18 y) treated with cinacalcet or parathyroidectomy for SHPT before receiving KT between 2007 and 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 with patients treated with cinacalcet, those treated with parathyroidectomy had a lower risk of developing THPT (adjusted hazard ratio, 0.56; 95% confidence interval, 0.35-0.89) post-KT. Furthermore, this risk differed by dialysis vintage (Pinteraction = 0.039). Among patients on maintenance dialysis therapy for ≥3 y before KT (n = 3477, 68.3%), the risk of developing THPT was lower when treated with parathyroidectomy (adjusted hazard ratio, 0.43; 95% confidence interval, 0.24-0.79). CONCLUSIONS: Parathyroidectomy should be considered as treatment for SHPT, especially in KT candidates on maintenance dialysis for ≥3 y. Additionally, patients treated with cinacalcet for SHPT should undergo close surveillance for development of tertiary hyperparathyroidism post-KT.

Is patient age associated with risk of malignancy in a ≥4 cm cytologically benign thyroid nodule?

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.

Understanding surgical decision-making in older adults with differentiated thyroid cancer: A discrete choice experiment.

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.

Features of synchronous versus metachronous metastasectomy in adrenal cortical carcinoma: Analysis from the US adrenocortical carcinoma database.

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: 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.

Surgical Approach to Endocrine Hypertension in Patients with Adrenal Disorders.

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.

What the radiologist needs to know: the role of preoperative computed tomography in selection of operative approach for adrenalectomy and review of operative techniques.

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.

Association Between Age and Patient-Reported Changes in Voice and Swallowing After Thyroidectomy.

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.

The association between the ultrasonography TIRADS classification system and surgical pathology among indeterminate thyroid nodules.

BACKGROUND: A high proportion of cytologically indeterminate, Afirma-suspicious thyroid nodules are benign. The Thyroid Imaging Reporting and Data System was proposed by the American College of Radiology in 2015 to determine appropriate management of thyroid nodules in a standardized fashion. Our aim was to determine the diagnostic value of the Thyroid Imaging Reporting and Data System in cytologically indeterminate and Afirma-suspicious nodules. METHODS: We retrospectively queried cytopathology archives for retrospectively for thyroid fine-needle aspiration specimens obtained between February 2012 and September 2016 that were associated with the following: (1) indeterminate diagnosis, (2) ultrasonographic imaging at our institution, (3) an Afirma Gene Expression Classifier-suspicious result, and (4) surgery at our institution. We then calculated the diagnostic value of the Thyroid Imaging Reporting and Data System in predicting surgical pathology. RESULTS: Our cohort consisted of 133 nodules among 131 patients who underwent thyroid surgery for cytologically indeterminate, Afirma-suspicious nodules. A total of 9 nodules (6.8%) were assigned TR2 "not suspicious," 25 (18.8%) TR3 "mildly suspicious," 81 (60.9%) TR4 "moderately suspicious," and 18 (13.5%) TR5 "highly suspicious." Among our cohort, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the Thyroid Imaging Reporting and Data System was 71.4%, 38.1%, 40.2%, 69.6%, and 50.4%, respectively. CONCLUSION: Among cytologically indeterminate and Afirma-suspicious nodules, the Thyroid Imaging and Reporting and Data System was a poor predictor of final surgical pathology. Additional prospective studies are needed to validate these findings.

Anterior cervical incision-sparing thyroidectomy: Comparing retroauricular and transoral approaches.

OBJECTIVES: The robotic retroauricular approach and transoral endoscopic thyroidectomy vestibular approach (TOETVA) have been employed to avoid anterior neck scarring in thyroidectomy with good success. However, outcomes have yet to be compared between techniques. We compare our initial clinical experience with these approaches for thyroid lobectomy at our institution. METHODS: A review of initial consecutive patients who underwent robotic facelift thyroidectomy (RFT) (August 2011-August 2016) at our institution was conducted. This was compared with the same number of initial consecutive patients who underwent TOETVA (September 2016-September 2017) at our institution. Demographics, operative time, pathology, complications, and learning curve were compared between cohorts. Learning curve was defined based on the slope of linear regression models of operative time versus case number. RESULTS: There were 20 patients in each cohort. There was no statistically significant difference in demographic data between cohorts. One hundred percent of RFT cases versus 95% TOETVA cases (P = .999) were completed without conversion to standard open technique with median operative times of 201 (124-293) minutes versus 188 (89-343) minutes with RFT and TOETVA, respectively (P = .36). There was no incidence of permanent recurrent laryngeal nerve injury in either cohort. The slopes of the regression models were 0.29 versus -8.32 (P = .005) for RFT and TOETVA, respectively. CONCLUSION: RFT and TOETVA are safe and feasible options for patients motivated to avoid an anterior neck scar. However, the quicker learning curve without the need for a costly robotic system may make TOETVA the preferred technique for institutions wishing to perform anterior cervical incision-sparing thyroidectomy. LEVEL OF EVIDENCE: 4.

Surgical Management of Normocalcemic Primary Hyperparathyroidism and the Impact of Intraoperative Parathyroid Hormone Testing on Outcome.

Objective To review our surgical experience and the impact of intraoperative parathyroid hormone (IOPTH) testing among patients with normocalcemic primary hyperparathyroidism. Study Design Case series with chart review. Setting Academic referral hospital. Subject and Methods Normocalcemic hyperparathyroidism (NCHPT) patients were identified with normal-range blood ionized calcium and serum elevated parathyroid hormone. Patient demographics, intraoperative findings, IOPTH dynamics, and biochemical outcomes were compared with those of classic primary hyperparathyroidism (PHPT) patients. Results Of the 2120 patients who underwent parathyroidectomy, 616 patients met the inclusion criteria: 119 (19.5%) patients had NCHPT, and 497 (80.5%) had classic PHPT. NCHPT patients had higher rates of multigland hyperplasia as compared with classic PHPT (12% vs 4%, P = .002) and smaller gland size ( P < .001). Of 119 NCHPT patients, 114 (97%) achieved >50% drop in IOPTH intraoperatively, as opposed to 492 (99%) among 497 classic PHPT patients ( P = .014). IOPTH drop >50% had an equivalent positive predictive value for long-term cure in both groups. Conclusions Surgeons treating NCHPT patients should suspect the presence of multigland disease and have a low threshold for converting to bilateral exploration depending on IOPTH decay dynamics.

An unusual etiology of hyperparathyroidism: robotic-assisted resection of a giant functional intrathymic parathyroid cyst.

Parathyroid cysts (PCs) are relatively rare entities, with an even smaller proportion that functionally produce parathyroid hormone (PTH). Given associated hypercalcemia, often symptomatic, as well as potentially related osteoporosis and/or nephrolithiasis, resection of these functional cysts is often indicated. This case report details the management course for a patient who presented with primary hyperparathyroidism and was ultimately found to have a functional intrathymic PC. During initial workup, 4-dimensional computed tomography (4D-CT) of the neck demonstrated enlarged left upper and right lower parathyroid glands; however, the patient's hyperparathyroid state persisted even after bilateral neck exploration and resection of these two glands. Subsequent postoperative imaging of the mediastinum revealed a large (11 cm) thymic cyst. The patient consequently underwent uneventful robotic-assisted thoracoscopic excision of the mediastinal cyst. Intraoperative blood PTH levels dropped from 734 pg/mL preoperatively to 86 pg/nL 10 minutes following resection, consistent with surgical cure by the Miami Criteria. At two months postoperatively, the patient's serum total calcium (STC) was normal at 9.2 mg/dL. Final surgical pathology noted a 15-gram parathyroid gland, with cystic degeneration. As the robot becomes further integrated into the everyday practice of thoracic surgery, we believe this approach offers advantages over conventional video-assisted thoracoscopic surgery (VATS) for mediastinal resections. Advantages include better visualization and finer, more precise dissection, especially important in this case, given the proximity of vital structures and the small, but real, risk of parathyromatosis associated with intraoperative cyst rupture.

A Novel T-Stage Classification System for Adrenocortical Carcinoma: Proposal from the US Adrenocortical Carcinoma Study Group.

BACKGROUND: The 7th AJCC T-stage system for adrenocortical carcinoma (ACC), based on size and extra-adrenal invasion, does not adequately stratify patients by survival. Lymphovascular invasion (LVI) is a known poor prognostic factor. We propose a novel T-stage system that incorporates LVI to better risk-stratify patients undergoing resection for ACC. METHOD: Patients undergoing curative-intent resections for ACC from 1993 to 2014 at 13 institutions comprising the US ACC Group were included. Primary outcome was disease-specific survival (DSS). RESULTS: Of the 265 patients with ACC, 149 were included for analysis. The current T-stage system failed to differentiate patients with T2 versus T3 disease (p = 0.10). Presence of LVI was associated with worse DSS versus no LVI (36 mo vs. 168 mo; p = 0.001). After accounting for the individual components of the current T-stage system (size, extra-adrenal invasion), LVI remained a poor prognostic factor on multivariable analysis (hazard ratio 2.14, 95% confidence interval 1.05-4.38, p = 0.04). LVI positivity further stratified patients with T2 and T3 disease (T2: 37 mo vs. median not reached; T3: 36 mo vs. 96 mo; p = 0.03) but did not influence survival in patients with T1 or T4 disease. By incorporating LVI, a new T-stage classification system was created: [T1: ≤ 5 cm, (-)local invasion, (+/-)LVI; T2: > 5 cm, (-)local invasion, (-)LVI OR any size, (+)local invasion, (-)LVI; T3: > 5 cm, (-)local invasion, (+)LVI OR any size, (+)local invasion, (+)LVI; T4: any size, (+)adjacent organ invasion, (+/-)LVI]. Each progressive new T-stage group was associated with worse median DSS (T1: 167 mo; T2: 96 mo; T3: 37 mo; T4: 15 mo; p < 0.001). CONCLUSIONS: Compared with the current T-stage system, the proposed T-stage system, which incorporates LVI, better differentiates T2 and T3 disease and accurately stratifies patients by disease-specific survival. If externally validated, this T-stage classification should be considered for future AJCC staging systems.

Are preoperative sestamibi scans useful for identifying ectopic parathyroid glands in patients with expected multigland parathyroid disease?

BACKGROUND: The role of preoperative localization studies in patients with hyperparathyroidism and expected multigland disease remains poorly defined. Our study investigates the usefulness of obtaining preoperative sestamibi scans and ultrasonography of the neck in identifying ectopic glands in this group of patients. METHODS: Under Institutional Review Board approval, we performed a retrospective review of patients who underwent operation for secondary hyperparathyroidism, tertiary hyperparathyroidism, lithium-induced hyperparathyroidism, and multiple endocrine neoplasia syndrome at a tertiary institution between 2004 and 2015. We reviewed patient demographics, laboratory, radiology, pathology, and operative reports. RESULTS: Of 2,975 parathyroidectomies performed during this period, 154 operations were performed in 149 patients who met the criteria. Of the 149 patients, 82 (55.0%) had secondary, 31 (20.8%) had tertiary, 23 (15.4%) had lithium-induced HPT, and 13 (10.1%) had multiple endocrine neoplasia syndrome; 86 ectopic glands were identified in 64 patients (43.0%). Sensitivity for identification of ectopic glands was 29% for sestamibi scan and 7% for ultrasonography, while 89% of mediastinal glands were localized by sestamibi scans and thoracotomy, thoracoscopy, or sternotomy occurred in 4.7% of patients. CONCLUSION: We found a greater rate of preoperative localization of ectopic glands than reported previously. Because the sensitivity of sestamibi for identification of ectopic glands is 23.0%, the implication of missing mediastinal glands warrants preoperative imaging.

Blood Transfusion and Survival for Resected Adrenocortical Carcinoma: A Study from the United States Adrenocortical Carcinoma Group.

Perioperative blood transfusion is associated with decreased survival in pancreatic, gastric, and liver cancer. The effect of transfusion in adrenocortical carcinoma (ACC) has not been studied. Patients with available transfusion data undergoing curative-intent resection of ACC from 1993 to 2014 at 13 institutions comprising the United States Adrenocortical Carcinoma Group were included. Factors associated with blood transfusion were determined. Primary and secondary end points were recurrence-free survival (RFS) and overall survival (OS), respectively. Out of 265 patients, 149 were included for analysis. Out of these, 57 patients (38.3%) received perioperative transfusions. Compared to nontransfused patients, transfused patients more commonly had stage 4 disease (46% vs 24%, P = 0.01), larger tumors (15.8 vs 10.2 cm, P < 0.001), inferior vena cava involvement (24.6% vs 5.4%, P = 0.002), additional organ resection (78.9% vs 36.3%, P < 0.001), and major complications (29% vs 2%, P < 0.001). Transfusion was associated with decreased RFS (8.9 vs 24.7 months, P = 0.006) and OS (22.8 vs 91.0 months, P < 0.001). On univariate Cox regression, transfusion, stage IV, hormonal hypersecretion, and adjuvant therapy were associated with decreased RFS. On multivariable analysis, only transfusion [hazard ratio (HR) = 1.7, 95% confidence interval (CI) =1.0-2.9, P = 0.04], stage IV (HR = 3.2, 95% CI = 1.7-5.9, P < 0.001), and hormonal hypersecretion (HR = 2.6, 95% CI = 1.5-4.2, P < 0.001) were associated with worse RFS. When applying this model to OS, similar associations were seen (transfusion HR = 2.0, 95% CI = 1.1-3.8, P = 0.02; stage 4 HR = 6.2, 95% CI = 3.1-12.4, P < 0.001; hormonal hypersecretion HR = 3.5, 95% CI = 1.9-6.4, P < 0.001). There was no difference in outcomes between patients who received 1 to 2 units versus >2 units of packed red blood cells in median RFS (8.9 vs 8.4 months, P = 0.95) or OS (26.5 vs 18.6 months, P = 0.63). Perioperative transfusion is associated with earlier recurrence and decreased survival after curative-intent resection of ACC. Strategies and protocols to minimize blood transfusion should be developed and followed.

Computed Tomography in the Management of Adrenal Tumors: Does Size Still Matter?

OBJECTIVE: We sought to evaluate computed tomography (CT) imaging as a predictor of adrenal tumor pathology. METHODS: A retrospective review was conducted of patients who underwent unilateral adrenalectomy for an adrenal mass between January 2005 and July 2015. Tumors were classified as benign, indeterminate, or malignant based on preoperative CT findings. RESULTS: Of 697 patients who underwent unilateral adrenalectomy, 216 met the inclusion criteria. Pathology was benign in 88.4%, indeterminate in 2.3%, and malignant in 9.3%, with a median tumor diameter of 2.7 cm (interquartile range, 1.7-4.1 cm) and 9.5 cm (interquartile range, 7.1-12 cm) in the benign and malignant groups, respectively (P < 0.001). Of the tumors with benign features on CT, 100% (143/143) had benign final pathology. CONCLUSIONS: Imaging characteristics of adrenal tumors on CT scan predict benign pathology 100% of the time. Regardless of size, when interpreted as benign on CT scan, laparoscopic adrenalectomy, if technically feasible, should be the technique used when surgery is offered, or close surveillance may be a safe alternative.

Curative Surgical Resection of Adrenocortical Carcinoma: Determining Long-term Outcome Based on Conditional Disease-free Probability.

OBJECTIVE: To evaluate conditional disease-free survival (CDFS) for patients who underwent curative intent surgery for adrenocortical carcinoma (ACC). BACKGROUND: ACC is a rare but aggressive tumor. Survival estimates are usually reported as survival from the time of surgery. CDFS estimates may be more clinically relevant by accounting for the changing likelihood of disease-free survival (DFS) according to time elapsed after surgery. METHODS: CDFS was assessed using a multi-institutional cohort of patients. Cox proportional hazards models were used to evaluate factors associated with DFS. Three-year CDFS (CDFS3) estimates at "x" year after surgery were calculated as follows: CDFS3 = DFS(x+3)/DFS(x). RESULTS: One hundred ninety-two patients were included in the study cohort; median patient age was 52 years. On presentation, 36% of patients had a functional tumor and median size was 11.5 cm. Most patients underwent R0 resection (75%) and 9% had N1 disease. Overall 1-, 3-, and 5-year DFS was 59%, 34%, and 22%, respectively. Using CDFS estimates, the probability of remaining disease free for an additional 3 years given that the patient had survived without disease at 1, 3, and 5 years, was 43%, 53%, and 70%, respectively. Patients with less favorable prognosis at baseline demonstrated the greatest increase in CDFS3 over time (eg, capsular invasion: 28%-88%, Δ60% vs no capsular invasion: 51%-87%, Δ36%). CONCLUSIONS: DFS estimates for patients with ACC improved dramatically over time, in particular among patients with initial worse prognoses. CDFS estimates may provide more clinically relevant information about the changing likelihood of DFS over time.