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

Poorman, Caroline E; Ethun, Cecilia G; Postlewait, Lauren M; Tran, Thuy B; Prescott, Jason D; Pawlik, Timothy M; Wang, Tracy S; Glenn, Jason; Hatzaras, Ioannis; Shenoy, Rivfka; Phay, John E; Keplinger, Kara; Fields, Ryan C; Jin, Linda X; Weber, Sharon M; Salem, Ahmed; Sicklick, Jason K; Gad, Shady; Yopp, Adam C; Mansour, John C; Duh, Quan-Yang; Seiser, Natalie; Solorzano, Carmen C; Kiernan, Colleen M; Votanopoulos, Konstantinos I; Levine, Edward A; Staley, Charles A; Poultsides, George A; Maithel, Shishir K
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.
PMCID:6087546
PMID: 29164414
ISSN: 1534-4681
CID: 2792322

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

Azoury, Saïd C; Nagarajan, Neeraja; Young, Allen; Mathur, Aarti; Prescott, Jason D; Fishman, Elliot K; Zeiger, Martha A
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.
PMID: 28107213
ISSN: 1532-3145
CID: 4859312

Characterizing the operative findings and utility of intraoperative parathyroid hormone (IOPTH) monitoring in patients with normal baseline IOPTH and normohormonal primary hyperparathyroidism

Trinh, Gina; Noureldine, Salem I; Russell, Jonathon O; Agrawal, Nishant; Lopez, Michael; Prescott, Jason D; Zeiger, Martha A; Tufano, Ralph P
BACKGROUND:During parathyroidectomy with intraoperative parathyroid hormone monitoring, the successful removal of a hypersecreting gland(s) resulting in normocalcemia is indicated by a >50% decrease in intraoperative parathyroid hormone level, typically into the normal range. Some patients, however, will have baseline parathyroid hormone levels within the normal range. We sought to determine the utility of intraoperative parathyroid hormone testing in these patients. METHODS:We retrospectively studied all patients who underwent parathyroidectomy for primary hyperparathyroidism at our institution over a 10-year period. RESULTS:Overall, 317 (17%) patients had parathyroid hormone within the normal range at the onset of operation (baseline intraoperative parathyroid hormone), and 1,544 (83%) had classic primary hyperparathyroidism. The intraoperative parathyroid hormone degradation was slower in normal baseline intraoperative parathyroid hormone patients than classic primary hyperparathyroidism patients, though this did not reach statistical significance (P < .254). A >50% intraoperative parathyroid hormone decrease predicted cure in 98.7% of normal baseline patients and 98.8% of classic primary hyperparathyroidism patients (P = .810). Normal baseline patients had a lesser cure rate the longer it took to achieve a 50% decrease intraoperatively; however, the cure rate was constant at any time point the 50% decrease occurred in patients with classic primary hyperparathyroidism (P < .05). CONCLUSION:The 50% rule delineating operative cure can be applied with equal confidence to patients with normal range, baseline intraoperative parathyroid hormone. Moreover, the time at which the 50% drop is achieved impacts operative success rates in these patients.
PMID: 27863787
ISSN: 1532-7361
CID: 4859302

A novel t-stage classification system for adrenocortical carcinoma: Proposal from the US Adrenocortical Carcinoma Study Group. [Meeting Abstract]

Poorman, Caroline Elizabeth; Ethun, Cecilia Grace; Postlewait, Lauren McLendon; Thuy Tran; Pawlik, Timothy M.; Wang, Tracy S.; Hatzaras, Ioannis; Phay, John E.; Fields, Ryan C.; Weber, Sharon M.; Sicklick, Jason K.; Yopp, Adam Charles; Prescott, Jason David; Duh, Quan-Yang; Solorzano, Carmen C.; Votanopoulos, Konstantinos Ioannis; Poultsides, George A.; Maithel, Shishir Kumar
ISI:000443281700259
ISSN: 0732-183x
CID: 4859522

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

Poorman, Caroline E; Postlewait, Lauren M; Ethun, Cecilia G; Tran, Thuy B; Prescott, Jason D; Pawlik, Timothy M; Wang, Tracy S; Glenn, Jason; Hatzaras, Ioannis; Shenoy, Rivfka; Phay, John E; Keplinger, Kara; Fields, Ryan C; Jin, Linda X; Weber, Sharon M; Salem, Ahmed; Sicklick, Jason K; Gad, Shady; Yopp, Adam C; Mansour, John C; Duh, Quan-Yang; Seiser, Natalie; Solorzano, Carmen C; Kiernan, Colleen M; Votanopoulos, Konstantinos I; Levine, Edward A; Staley, Charles A; Poultsides, George A; Maithel, Shishir K
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.
PMCID:6054878
PMID: 28738949
ISSN: 1555-9823
CID: 2652172

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

Kim, Yuhree; Margonis, Georgios A; Prescott, Jason D; Tran, Thuy B; Postlewait, Lauren M; Maithel, Shishir K; Wang, Tracy S; Glenn, Jason A; Hatzaras, Ioannis; Shenoy, Rivfka; Phay, John E; Keplinger, Kara; Fields, Ryan C; Jin, Linda X; Weber, Sharon M; Salem, Ahmed; Sicklick, Jason K; Gad, Shady; Yopp, Adam C; Mansour, John C; Duh, Quan-Yang; Seiser, Natalie; Solorzano, Carmen C; Kiernan, Colleen M; Votanopoulos, Konstantinos I; Levine, Edward A; Poultsides, George A; Pawlik, Timothy M
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%, Delta60% vs no capsular invasion: 51%-87%, Delta36%). 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.
PMCID:4974140
PMID: 28009746
ISSN: 1528-1140
CID: 2374602

Minimally Invasive Resection of Adrenocortical Carcinoma: a Multi-Institutional Study of 201 Patients

Lee, Christina W; Md, Ahmed I Salem; Schneider, David F; Leverson, Glen E; Tran, Thuy B; Poultsides, George A; Postlewait, Lauren M; Maithel, Shishir K; Wang, Tracy S; Hatzaras, Ioannis; Shenoy, Rivfka; Phay, John E; Shirley, Lawrence; Fields, Ryan C; Jin, Linda X; Pawlik, Timothy M; Prescott, Jason D; Sicklick, Jason K; Gad, Shady; Yopp, Adam C; Mansour, John C; Duh, Quan-Yang; Seiser, Natalie; Solorzano, Carmen C; Kiernan, Colleen M; Votanopoulos, Konstantinos I; Levine, Edward A; Weber, Sharon M
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
PMCID:5263186
PMID: 27770290
ISSN: 1873-4626
CID: 2280212

CT Appearance of Adrenal Cystic Lymphangioma: Radiologic-Pathologic Correlation

Rowe, Steven P; Bishop, Justin A; Prescott, Jason D; Salvatori, Roberto; Fishman, Elliot K
OBJECTIVE:Cystic lymphangioma is an uncommon lesion in the adrenal gland. Because of the lesion's rarity, few descriptions of it can be found in the radiology literature. We therefore describe a series of these lesions with a focus on CT characteristics with correlation to gross and microscopic pathology features. MATERIALS AND METHODS/METHODS:Retrospective review identified seven patients with definitive pathologic findings of cystic lymphangioma of the adrenal gland and available diagnostic CT examinations. CT examinations were reviewed for key imaging features and correlated to gross and microscopic pathology. Lesions were generally described in corresponding reports as likely representing adenomas or hematomas based on CT findings. RESULTS:All cystic lymphangiomas included in this series were well-circumscribed lesions with low-attenuation internal contents and thin walls, without evidence of solid components or nodularity. No measurable contrast enhancement was seen in these lesions. Six of the seven lesions contained calcifications with one of two patterns: either thick, curvilinear, and dystrophic-appearing or thin and scattered. On gross and microscopic pathology, the lesions were composed of dilated cystic spaces containing serous fluid and lined by bland endothelial cells. CONCLUSION/CONCLUSIONS:Though rare, an adrenal cystic lymphangioma should be suspected on CT when a unilocular or multilocular, low-attenuation, nonenhancing lesion is present in the region of the adrenal gland, particularly if the lesion contains either of the above-noted calcification patterns. Recognition of these findings may allow more conservative treatment of selected patients harboring these lesions.
PMID: 26700338
ISSN: 1546-3141
CID: 4859272

Evaluation of the Effect of Diagnostic Molecular Testing on the Surgical Decision-Making Process for Patients With Thyroid Nodules

Noureldine, Salem I; Najafian, Alireza; Aragon Han, Patricia; Olson, Matthew T; Genther, Dane J; Schneider, Eric B; Prescott, Jason D; Agrawal, Nishant; Mathur, Aarti; Zeiger, Martha A; Tufano, Ralph P
IMPORTANCE:Diagnostic molecular testing is used in the workup of thyroid nodules. While these tests appear to be promising in more definitively assigning a risk of malignancy, their effect on surgical decision making has yet to be demonstrated. OBJECTIVE:To investigate the effect of diagnostic molecular profiling of thyroid nodules on the surgical decision-making process. DESIGN, SETTING, AND PARTICIPANTS:A surgical management algorithm was developed and published after peer review that incorporated individual Bethesda System for Reporting Thyroid Cytopathology classifications with clinical, laboratory, and radiological results. This algorithm was created to formalize the decision-making process selected herein in managing patients with thyroid nodules. Between April 1, 2014, and March 31, 2015, a prospective study of patients who had undergone diagnostic molecular testing of a thyroid nodule before being seen for surgical consultation was performed. The recommended management undertaken by the surgeon was then prospectively compared with the corresponding one in the algorithm. Patients with thyroid nodules who did not undergo molecular testing and were seen for surgical consultation during the same period served as a control group. MAIN OUTCOMES AND MEASURES:All pertinent treatment options were presented to each patient, and any deviation from the algorithm was recorded prospectively. To evaluate the appropriateness of any change (deviation) in management, the surgical histopathology diagnosis was correlated with the surgery performed. RESULTS:The study cohort comprised 140 patients who underwent molecular testing. Their mean (SD) age was 50.3 (14.6) years, and 75.0% (105 of 140) were female. Over a 1-year period, 20.3% (140 of 688) had undergone diagnostic molecular testing before surgical consultation, and 79.7% (548 of 688) had not undergone molecular testing. The surgical management deviated from the treatment algorithm in 12.9% (18 of 140) with molecular testing and in 10.2% (56 of 548) without molecular testing (P = .37). In the group with molecular testing, the surgical management plan of only 7.9% (11 of 140) was altered as a result of the molecular test. All but 1 of those patients were found to be overtreated relative to the surgical histopathology analysis. CONCLUSIONS AND RELEVANCE:Molecular testing did not significantly affect the surgical decision-making process in this study. Among patients whose treatment was altered based on these markers, there was evidence of overtreatment.
PMID: 27196108
ISSN: 2168-619x
CID: 4859282

Computed Tomography Appearance of Surgically Resected Adrenal Hematomas

Rowe, Steven P; Mathur, Aarti; Bishop, Justin A; Epstein, Jonathan I; Prescott, Jason D; Salvatori, Roberto; Siegelman, Stanley S; Fishman, Elliot K
OBJECTIVE:Adrenal hemorrhages arise as a result of a number of conditions and may exhibit a variety of appearances on computed tomography (CT). On occasion, patients will undergo adrenalectomy for treatment of a presumptive adrenal neoplasm that on surgical pathology is identified as an adrenal hemorrhage. We evaluated the CT appearance of surgically resected adrenal masses from our institution over a period of 15 years that ultimately proved to be adrenal hematomas. METHODS:A surgical pathology archive was queried for all cases of adrenal hemorrhage. Only cases with a corresponding diagnostic CT were included. Cases were excluded if an underlying adrenal mass was present. For the remaining cases, the CT appearances were evaluated by 2 radiologists quantitatively and qualitatively. RESULTS:Our search yielded 18 cases of adrenal hemorrhage, of which 5 cases had corresponding CT and no underlying secondary process within the adrenal. All of the adrenal hematomas in this series demonstrated an ovoid morphology and were well defined, with an average maximum diameter of 8.9 cm and highly variable attenuation on noncontrast CT (average attenuation range, 13.1-44.0 Hounsfield units [HU]). Four of the 5 lesions had degrees of peripheral enhancement that was either thin and somewhat uniform or heterogeneous and irregular. None of the lesions demonstrated invasion of the periadrenal fat or adjacent organs. CONCLUSIONS:Adrenal hematomas with a mass-like configuration offer a potential diagnostic dilemma for radiologists and surgeons. Although it is rare that an adrenal hemorrhage is surgically resected, awareness of the potential appearances of these lesions is important to spare patients from unnecessarily aggressive surgery.
PMID: 27560014
ISSN: 1532-3145
CID: 4859292