Faculty Bibliography

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 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.

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.

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.

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.

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.

BACKGROUND AND OBJECTIVES: Minimally invasive surgery for adrenocortical carcinoma (ACC) is controversial. We sought to evaluate the perioperative and long-term outcomes following minimally invasive (MIS) and open resection (OA) of ACC in patients treated with curative intent surgery. METHODS: Retrospective data from patients who underwent adrenalectomy for primary ACC at 13 tertiary care cancer centers were analyzed, including demographics, clinicopathological, and operative outcomes. Outcomes following MIS were compared to OA. RESULTS: A total of 201 patients were evaluated including 47 MIS and 154 OA. There was no difference in utilization of MIS approach among institutions (p = 0.24) or 30-day morbidity (29.3 %, MIS, vs. 30.9 %, OA; p = 0.839). The only preoperatively determined predictor for MIS was smaller tumor size (p < 0.001). There was no difference in rates of intraoperative tumor rupture (p = 0.612) or R0 resection (p = 0.953). Only EBL (p = 0.038) and T stage (p = 0.045) were independent prognostic indicators of overall survival after adjusting for significant factors. The surgical approach was not associated with overall or disease-free survival. CONCLUSION: MIS adrenalectomy may be utilized for preoperatively determined ACC