Thyroglobulin Measurement in Fine-Needle Aspiration Improves the Diagnosis of Cervical Lymph Node Metastases in Papillary Thyroid Carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) is frequently associated with cervical lymph node metastases. Guidelines recommend performing ultrasound-guided fine-needle aspiration cytology (FNAC) for suspicious nodes to guide management. No specific recommendations are available for the use of FNA thyroglobulin assay (FNA-Tg). This study investigated the diagnostic value of performing FNAC and FNA-Tg. METHODS: Patient demographics, preoperative investigations, surgery, and lymph node pathology were collected for patients with PTC who underwent lateral neck lymphadenectomy and central compartment reexploration from January 2000 to July 2015. Sensitivities and accuracies were obtained. Patients with both diagnostic studies performed were compared using McNemar's test of paired proportion. Patient, imaging, and lymph node characteristics were correlated with test accuracy. RESULTS: The 480 patients in this study underwent 706 lateral neck dissections or central compartment reexploration. All the patients underwent preoperative neck ultrasound. Among these patients, FNAC alone was performed before 426 operations (60 %), FNAC with FNA-Tg before 105 operations (15 %), and surgery without biopsy for 175 patients (25 %). The sensitivity, positive predictive value, and accuracy were respectively 96, 95, 100 % for FNAC, 99, 97, and 97 % for FNA-Tg, and 95, 92, and 97 % for FNAC in combination with FNA-Tg. In the subgroup of patients who had both tests performed, the sensitivity of FNA-Tg was superior to that of FNAC (95 vs 87 %; p = 0.04). The addition of FNA-Tg to FNAC increased the detection of metastatic PTC by 13 %. CONCLUSIONS: For diagnosing cervical lymph node metastases in PTC, FNA-Tg is a valuable adjunct to FNAC. Its use should be considered to avoid missing metastatic disease in patients who may benefit from lymphadenectomy.

Surgical Treatment of Malignant Pheochromocytoma and Paraganglioma: Retrospective Case Series.

INTRODUCTION: Pheochromocytoma and paraganglioma (PPGL) are rare neoplasms; about 10% are malignant. Literature regarding possible benefit from resection is extremely limited. METHODS: A 20 year review of all patients undergoing surgery for malignant PPGL at the Mayo Clinic Rochester Campus between 1994 and June 2014 was performed. RESULTS: We identified 34 patients undergoing surgery for malignant PPGL. Median follow up was 6 and 5 years survival was 90% (median 11 years). Complete resection (R0) was achieved in 14 patients (41%). Median disease-free survival was 4.6 years for patients with R0 resection (up to 12 years). Only eight patients (23%) were disease-free on last follow up. Elevated preoperative fractionated metanephrines or catecholamines were documented in 23 patients (68%); these normalized in 13 of 23 patients (56%) postoperatively-with symptom relief in 15 of 18 preoperatively symptomatic patients (79%). Among 23 patients with hormone-producing tumors, significant reduction in number of antihypertensive medications was also noted postoperatively; 11 patients have remained off all antihypertensives, 6 required 1 medication, 1 required 2, while 5 required full blockade with phenoxybenzamine and a beta-adrenergic blocker. CONCLUSION: Surgery plays a significant role in the management of selected malignant PPGL. Resection can be effective in normalizing or significantly reducing levels of catecholamines and metanephrines, and can improve hormone-related symptoms and hypertension. Surgical resection, either complete or incomplete, is associated with durable survival despite a high rate of tumor recurrence.

Pheochromocytoma with Synchronous Ipsilateral Adrenal Cortical Adenoma.

BACKGROUND: Pheochromocytoma with synchronous ipsilateral adrenal cortical adenoma (PSCA) may present with mixed clinical, biochemical, and radiological features characteristic to each neoplasm subtype. METHODS: All patients with a pathological diagnosis of pheochromocytoma were evaluated for an ipsilateral cortical adenoma from 1994 through 2015. Retrospectively extracted data included indications for adrenalectomy, diagnostic workup (biochemical and radiographic), operative characteristics, pathological findings, and postoperative complications. RESULTS: Sixteen of 413 patients (4%) undergoing adrenalectomy for pheochromocytoma had a PSCA. Median patient age was 57.7 years (IQR 50.1, 63.1); 50% were male. On imaging, 75% of the adrenal neoplasms were found incidentally and only 50% were reported to have a synchronous ipsilateral neoplasm based on imaging findings. Clinically important cortical hormone secretion was diagnosed in 38% of these patients; 25% had glucocorticoid secretory autonomy; and 13% had primary aldosteronism. CONCLUSION: Physicians should be aware that adrenal neoplasms with mixed diagnostic findings may represent PSCA. Evaluation should be performed on this co-occurrence to prevent perioperative complications from resection of an unexpected secretory cortical neoplasm.

Robotic single-site adrenalectomy.

INTRODUCTION: Technological advances have brought about robotic single-site (RSS) cholecystectomy and hysterectomy. The application of RSS to additional procedures requires careful assessment of the surgeon learning curve, the technological limitations, patient selection criteria and associated outcomes. METHODS: Patient demographics, BMI, surgical indications, adrenal size, OR times, length of stay, postoperative pain and complications were assessed. RESULTS: Thirty-three patients underwent RSS-A by a single surgeon with 53 % being male, mean age 54 ± 16 years and mean BMI of 32.7. There were 18 left, 10 right, and 5 bilateral procedures for a total of 38 adrenal glands removed (mean tumor size 3.2 cm). There were 5 conversions to a laparoscopic approach, and two to open approach. The necessity for conversion was not associated with age, BMI, tumor size, surgical side or pathology (p > 0.05). The patients who underwent successful unilateral RSS-A had a profile of mean age 55, BMI 31, tumor size 3 cm, and a mean operative time of 118 ± 25.8 min. Pain scores were <4 (10 point scale) in 67 % of patients. 74 % of patients were discharged on POD 1 and 96 % were discharged by POD 2. An assessment of the quartile learning curve for the unilateral RSS-A showed operative times decreased from a mean of 124 to 103 min after 21 cases (p = 0.05). CONCLUSION: Patients with functioning and non-functioning tumors, along with those with obesity can safely be treated with RSS-A. The surgeon learning curve was associated with shortened operative times and not increased complication rates.

A Multimodal Imaging Protocol, (123)I/(99)Tc-Sestamibi, SPECT, and SPECT/CT, in Primary Hyperparathyroidism Adds Limited Benefit for Preoperative Localization.

INTRODUCTION: Focused parathyroidectomy in primary hyperparathyroidism (1°HPT) is possible with accurate preoperative localization and intraoperative PTH monitoring (IOPTH). The added benefit of multimodal imaging techniques for operative success is unknown. METHOD: Patients with 1°HPT, who underwent parathyroidectomy in 2012-2014 at a single institution, were retrospectively reviewed. Only the patients who underwent the standardized multimodal imaging workup consisting of (123)I/(99)Tc-sestamibi subtraction scintigraphy, SPECT, and SPECT/CT were assessed. RESULTS: Of 360 patients who were identified, a curative operation was performed in 96%, using pre-operative imaging and IOPTH. Imaging analysis showed that (123)I/(99)Tc-sestamibi had a sensitivity of 86% (95% CI 82-90%), positive predictive value (PPV) 93%, and accuracy 81%, based on correct lateralization. SPECT had a sensitivity of 77% (95% CI 72-82%), PPV 92% and accuracy 72%. SPECT/CT had a sensitivity of 75% (95% CI 70-80%), PPV of 94%, and accuracy 71%. There were 3 of 45 (7%) patients with negative sestamibi imaging that had an accurate SPECT and SPECT/CT. Of 312 patients (87%) with positive uptake on sestamibi (93% true positive, 7% false positive), concordant findings were present in 86% SPECT and 84% SPECT/CT. In cases where imaging modalities were discordant, but at least one method was true-positive, (123)I/(99)Tc-sestamibi was significantly better than both SPECT and SPECT/CT (p < 0.001). The inclusion of SPECT and SPECT/CT in 1°HPT imaging protocol increases patient cost up to 2.4-fold. CONCLUSION: (123)I/(99)Tc-sestamibi subtraction imaging is highly sensitive for preoperative localization in 1°HPT. SPECT and SPECT/CT are commonly concordant with (123)I/(99)Tc-sestamibi and rarely increase the sensitivity. Routine inclusion of multimodality imaging technique adds minimal clinical benefit but increases cost to patient in high-volume setting.

Selective Parathyroid Hormone Venous Sampling in Patients with Persistent or Recurrent Primary Hyperparathyroidism and Negative, Equivocal or Discordant Noninvasive Imaging.

BACKGROUND: In patients with persistent (P-PHPT) or recurrent (R-PHPT) primary hyperparathyroidism, preoperative localization is important. Selective parathyroid hormone venous sampling (sPVS) is an invasive technique that can be used to regionalize and/or lateralize the source of PHPT when noninvasive imaging studies are nonlocalizing. The aim of the present study was to assess the role of sPVS in the preoperative evaluation of patients with P-PHPT or R-PHPT and negative, equivocal, or discordant noninvasive imaging localization. METHODS: After IRB-approval a retrospective review of all patients with P-PHPT or R-PHPT and nonlocalizing noninvasive imaging that underwent sPVS from 2000 to 2014 was performed. The location of the source of PHPT at sPVS was predicted by a parathyroid hormone (PTH) gradient and compared to the surgical, pathology, and biochemical follow-up data as the gold standard. Sensitivity and positive predictive value (PPV) were calculated. RESULTS: Of 30 patients who underwent sPVS, 12 patients did not undergo surgical exploration due to negative or non-localizing PTH gradient (n = 8) or opted for medical management (n = 4). Of the 18 patients who underwent surgical exploration, 17 (94 %) had a positive PTH gradient and pathologic parathyroid tissue identified at surgery. Sensitivity and PPV of sPVS were 93 and 77 %, respectively, for all surgical cases, 86 and 60.0 % for cervical cases (n = 11), and 100 and 100 % for mediastinal cases (n = 7). Sixteen patients (89 %) were surgically cured. CONCLUSIONS: In patients with P-PHPT or R-PHPT and nonlocalizing imaging studies, sPVS is a sensitive test for localizing the source of PHPT when a positive PTH gradient is present.

Surgical resection of synchronously metastatic adrenocortical cancer.

INTRODUCTION: Metastatic adrenocortical carcinoma (ACC) is rapidly fatal, with few options for treatment. Patients with metachronous recurrence may benefit from surgical resection. The survival benefit in patients with hematogenous metastasis at initial presentation is unknown. METHODS: A review of all patients undergoing surgery (European Network for the Study of Adrenal Tumors) stage IV ACC between January 2000 and December 2012 from two referral centers was performed. Kaplan-Meier estimates were analyzed for disease-free and overall survival (OS). RESULTS: We identified 27 patients undergoing surgery for stage IV ACC. Metastases were present in the lung (19), liver (11), and brain (1). A complete resection (R0) was achieved in 11 patients. The median OS was improved in patients undergoing R0 versus R2 resection (860 vs. 390 days; p = 0.02). The 1- and 2-year OS was also improved in patients undergoing R0 versus R2 resection (69.9 %, 46.9 % vs. 53.0 %, 22.1 %; p = 0.02). Patients undergoing neoadjuvant therapy (eight patients) had a trend towards improved survival at 1, 2, and 5 years versus no neoadjuvant therapy (18 patients) [83.3 %, 62.5 %, 41.7 % vs. 56.8 %, 26.6 %, 8.9 %; p = 0.1]. Adjuvant therapy was associated with improved recurrence-free survival at 6 months and 1 year (67 %, 33 % vs. 40 %, 20 %; p = 0.04) but not improved OS (p = 0.63). Sex (p = 0.13), age (p = 0.95), and location of metastasis (lung, p = 0.51; liver, p = 0.67) did not correlate with OS after operative intervention. Symptoms of hormonal excess improved in 86 % of patients. CONCLUSION: Operative intervention, especially when an R0 resection can be achieved, following systemic therapy may improve outcomes, including OS, in select patients with stage IV ACC. Response to neoadjuvant chemotherapy may be of use in defining which patients may benefit from surgical intervention. Adjuvant therapy was associated with decreased recurrence but did not improve OS.

Reoperative experience with papillary thyroid cancer.

BACKGROUND: Intense postoperative monitoring has resulted in increasing detection of patients with recurrent papillary thyroid cancer (PTC). Our goals included quantifying successful reoperation, and analyzing surgical complications and reasons for relapse. METHODS: From 1999 to 2008, a total of 410 patients underwent reoperation for PTC relapse. We analyzed post-reoperative disease outcomes, reasons for relapse, and complications. RESULTS: Bilateral reoperative thyroidectomy was performed in 13 (3 %) patients; lobectomy, 34 (8 %); central neck (VI) soft tissue local recurrence excision, 47 (11.5 %); bilateral VI node dissection, 107 (26 %); unilateral VI dissection, 112 (27 %); levels II-V dissection, 93 (23 %); levels III-V, 86 (21 %); lateral single- or two-compartment dissection, 51 (12 %); and node picking, 20 (5 %) of level VI and 53 (13 %) lateral neck. Complications occurred in 6 %; including hypoparathyroidism, 3 %; unintentional recurrent laryngeal nerve (RLN) paralysis, 3 %; phrenic nerve injury, 0.5 %; spinal accessory nerve injury, 0.5 %; and chyle leak in 1.6 %. Of 380 (93 %) patients with follow-up (mean 5.2 years); 274 (72 %) patients are alive with no structural evidence of disease, 38 % developed disease relapse (mean 2.1 years), 42 (11 %) died from PTC, and 55 (14 %) are alive with disease. The reason for relapse was a false negative pre-reoperative ultrasound (US) in 18 (5 %), nodal recurrence in the operative field in 37 (10 %), a combination of these two reasons in 10 (3 %), and disease virulence (local or systemic recurrence) in 81 (21 %). CONCLUSIONS: Although 72 % of patients were rendered structurally disease free after reoperation, nearly 40 % suffered additional relapse. Improved surgical technique or preoperative localization might positively affect 15-20 %; at least 20 % reflect the biologic aggressiveness of the disease.

Thyroid cancer detection with dual-isotope parathyroid scintigraphy in primary hyperparathyroidism.

BACKGROUND: Thyroid cancer cells have been shown to take up (99m)Tc-sestamibi. The role for (99m)Tc-sestamibi scintigraphy (Tc-MIBI) in the diagnosis of thyroid cancer in patients with primary hyperparathyroidism (PHPT) is unclear. Our aim was to determine whether dual-isotope parathyroid scintigraphy is useful in identifying thyroid cancer. METHODS: A prospective database of 3,187 patients who underwent neck exploration for PHPT was reviewed to identify patients who had concurrent thyroid resection. Patients with benign and malignant thyroid disease were comparatively analyzed. RESULTS: A total of 470 patients underwent both thyroidectomy and parathyroidectomy (reoperations in 21%). Benign disease (n = 391, 83%) was more common than malignancy [papillary thyroid cancer (n = 75) and medullary thyroid cancer (n = 5); 1 had both]. Dual-isotope scintigraphy obtained in 374 patients (80%) had a sensitivity of 67% and a positive predictive value of 66% for parathyroid adenoma localization in these patients with thyroid disease. False-positive scintigraphy occurred in 22% with benign and 45% with malignant thyroid disease (P = 0.002). On Tc-MIBI imaging, 54 (86%) of 63 patients with malignancy had hot nodules, compared to 248 (81%) of 308 patients with benign disease (P = 0.49). On I-123 imaging, 34 (54%) of 63 patients with malignancy had cold nodules, compared to 42 (14%) of 304 patients with benign disease (P < 0.001). A dual-isotype phenotype of both Tc-MIBI-Hot and I-123-Cold had sensitivity 52%, specificity 88%, positive predictive value 47%, and negative predictive value 90% for detecting a thyroid malignancy. CONCLUSIONS: A Tc-MIBI-Hot/I-123-Cold phenotype is very specific for detecting thyroid malignancy. Patients with this imaging phenotype should strongly be considered for preoperative ultrasound-guided biopsy. Patients found intraoperatively to have false-positive parathyroid scintigraphy should be evaluated for thyroid cancer.

Primary hyperparathyroidism and negative Tc99 sestamibi imaging: to operate or not?

BACKGROUND: The indications for surgery in primary hyperparathyroidism (1HPT) are the same for patients with and without localization on imaging. However, patients with negative imaging may not be referred for surgery or the surgeon may be reluctant to operate. We compare outcomes in patients with negative imaging to those with localization. METHODS: A review of patients who underwent primary operation for 1HPT with a preoperative Tc99 sestamibi I-123 (MIBI) scan was conducted. Imaging, laboratory, operative findings, pathologic findings, and outcomes were used to compare patients with negative scans to those with localization. RESULTS: A total of 2,681 patients had an operation for 1HPT with preoperative MIBI. MIBI imaging was negative in 136 (5.7 %). The negative MIBI group had a lower calcium (10.9 vs. 11.0 mg/ml, P=0.02), phosphorus (2.9 vs. 3.1 mg/dl, P<0.001), and urinary calcium (251 vs. 287 mg/ml, P=0.02) and no difference in parathyroid hormone, 25-OH vitamin D, or bone loss. Multigland resection was higher with a negative scan (32 vs. 13 %, P<0.001). A curative operation was performed in 90.4 % with a negative MIBI compared to 97.5 % with localization (P<0.001). Patients who underwent successful surgery despite a negative MIBI scan had lower calcium (10.8 vs. 11.1 mg/ml, P=0.04) and parathyroid hormone (98 vs. 196 pg/ml, P=0.03) than those not cured. Patients with both a negative ultrasound result and negative MIBI had a cure rate of 89 %. CONCLUSIONS: A curative operation is performed at an acceptably lower rate with negative MIBI imaging. A decision for surgery with a negative MIBI finding should consider lower cure rates and symptom severity.

Adrenalectomy improves outcomes of selected patients with metastatic carcinoma.

BACKGROUND: Indications and survival benefit for adrenalectomy (ADX) in the setting of metastasis are not clearly defined. We aimed to determine which patients with primary malignancies may benefit from ADX performed for metastasis. Mayo Clinic institutional outcomes in patients with metastatic disease to the adrenal(s) treated by adrenalectomy were compared to stage-matched historical controls from the Surveillance Epidemiology and End Results (SEER) database. METHODS: A retrospective review (1992-2010) was conducted to identify patients treated with ADX for metastatic cancer at Mayo Clinic, Rochester. Associations of clinical, surgical, and pathologic features with overall survival (OS) were evaluated using Cox proportional regression models. OS for those treated with ADX was compared with that for SEER database stage-matched patients who underwent primary resection without resection of distant disease using log-rank tests. RESULTS: A total of 166 patients underwent ADX for metastatic primaries involving the kidney 60, lung 24, sarcoma 19, colon 15, pancreas 13, and other-35. Patients with sarcoma and kidney, lung, and pancreatic tumors who underwent ADX had better OS at 1, 2, and 3 years than did the SEER-matched controls. Respectively, the rates were for sarcoma (100, 93, 86% vs. 57, 36, 30%), kidney (86, 80, 72% vs. 55, 37, 27%), lung (91, 69, 52% vs. 52, 34, 25%), and pancreas (79, 56, 45% vs. 33, 20, 12%). Univariate analysis identified primary diagnosis <2 years before ADX, other distant site, pancreatic primary, palliative operation, and persistent disease as risk factors for death. CONCLUSIONS: An aggressive surgical approach results in improved OS in patients with metastatic disease arising from soft tissues, kidney, lung, and pancreas. Other tumors may benefit, but larger study cohorts are needed for a meaningful comparison.

Setting the bar for laparoscopic resection of sporadic insulinoma.

BACKGROUND: Laparoscopic insulinoma resection (LIR) for sporadic disease is increasingly supported as a feasible and safe operation in small series of patients. To determine whether LIR is an acceptable alternative to the open operation, it is necessary to compare LIR to historical controls. The purpose of this study was to identify the skills and technology needed for LIR and establish outcome standards. METHODS: A database of patients with benign sporadic insulinoma who underwent an open procedure at the Mayo Clinic was reviewed for demographics, imaging, operative/pathology reports, and outcomes. Outcomes were compared to a world-wide meta-analysis of patients who had undergone LIR reported in the English literature between 1996 and 2009. RESULTS: Two hundred fifteen patients underwent a primary open operation for benign sporadic insulinoma. Solitary tumors were found in 97%. Meta-analysis identified 232 patients who underwent LIR. The open and LIR groups underwent comparable operations that included enucleations (64 vs. 68%) and distal pancreatectomies (28 vs. 35%) (p = 0.06). The mean estimated blood loss, operating time, and length of stay were comparable between the open and LIR groups (p = NS). Pancreatic fistula occurred more often in the LIR group (24 vs. 11%, p < 0.05). A curative operation was performed in 98% of control patients and in 99% of the LIR group (p = NS). CONCLUSIONS: Multiple insulinomas are rare and a focused resection guided by imaging may be performed. LIR is associated with an increased incidence of pancreatic fistula. Success of LIR will depend on accurate multimodality preoperative imaging, skilled use of lap-US to replace palpation for localization, and safe methods to dissect the tumor adjacent to the pancreatic duct.

Effects of propofol on intraoperative parathyroid hormone monitoring in patients with primary hyperparathyroidism undergoing parathyroidectomy: a randomized control trial.

PURPOSE: Serial measurements of parathyroid hormone (PTH) serum concentrations aid parathyroidectomy surgery. There are concerns that propofol may increase PTH concentrations and/or interfere with PTH assays. The primary purpose of this study is to determine the effects of propofol on PTH concentrations in patients with primary hyperparathyroidism and to determine its effect on PTH assays. METHODS: Thirty patients with primary hyperparathyroidism were assigned randomly to induction and maintenance with either propofol or sevoflurane. Blood samples for PTH assays were obtained pre-induction, immediately after induction, ten minutes after induction, and after excision of parathyroid adenoma. The primary endpoint was the PTH concentration at ten minutes after induction. This endpoint was compared between groups using analysis of covariance adjusting for pre-induction PTH. An in vitro study was performed with four different pools of PTH concentrations that were spiked with increasing concentrations of propofol. Serum PTH was measured in duplicate in each sample and analyzed using repeated measures analysis of variance. RESULTS: At ten minutes after induction, PTH concentrations did not differ significantly between groups (least square mean difference -7.0 pg·mL(-1); 95% confidence interval, -34.2 to +20.2). The PTH level in vitro did not change significantly with increasing propofol concentrations. DISCUSSION: Parathyroid hormone concentrations in patients with primary hyperparathyroidism were not affected by the type of anesthesia (propofol vs sevoflurane). Furthermore, propofol was found not to interfere with PTH assays at clinically relevant concentrations. There is no evidence to support the avoidance of a propofol anesthetic for parathyroid surgery.

Malignant adrenal neoplasm masquerading as worrisome adrenal hemorrhage.

BACKGROUND: Adrenal hemorrhage (AH) associated with adrenal neoplasm is rare. This study assesses the clinical and pathological impact of AH in the setting of malignant adrenal neoplasm to establish management strategies. MATERIALS AND METHODS: Patients admitted over a 25-year period with a diagnosis of AH and malignant adrenal neoplasm were retrospectively reviewed. RESULTS: Malignant adrenal neoplasms were reported in 14 of 217 patients (6.4%) presenting with AH. Of these, 4 were women. Mean age was 56 years. The most common presenting symptom was abdominal pain (n = 6), followed by altered mental status and shock (2) and hypercortisolism (1). Five patients were asymptomatic. In 10 patients the adrenal tumor was metastatic. Four patients had adrenocortical carcinoma (ACC). All primary adrenal tumors were unilateral. Risk factors for AH were identified in 5 patients (anticoagulation, 3; trauma, 1; and recent surgery, 1). Computed tomography (n = 12) demonstrated adrenal masses ranging in size from 6.8 to 11.0 cm (mean, 9 cm). Nine patients were managed by surgical resection (adrenalectomy, 4; radical nephrectomy, 2; adrenalectomy/splenectomy, 1; adrenalectomy/bowel resection, 1; and laparotomy and packing, 1) Actual survival time ranged from 9 days to 7.8 years (median 329 days). CONCLUSION: Most patients with AH in the setting of malignant adrenal neoplasm had metastatic tumors to the adrenal glands. These patients do not typically present in hemorrhagic shock, allowing for adequate preoperative evaluation for function and assessment for primary tumors. Long-term survival of these patients is rare.

Risks and adequacy of an optimized surgical approach to the primary surgical management of papillary thyroid carcinoma treated during 1999-2006.

BACKGROUND: Intense disease surveillance and frequent lymph node metastases (LNMs) in papillary thyroid cancer (PTC) have resulted in increased locoregional recurrences. We examined the safety and efficacy of an optimized surgical approach including preoperative ultrasonography (US), bilateral thyroidectomy, routine compartment VI dissection, and lateral neck dissection for LNM. METHODS: During 1999-2006, a total of 420 patients underwent optimized primary surgery; 291(69%) females, median age 46 years; follow-up 98%, median 4.4 years. Patients were reviewed for tumor characteristics, pattern of LNM, staging, and outcomes. RESULTS: Total or near-total thyroidectomy was performed in 212 (51%) and 208 (49%) patients, respectively. Tumors were multicentric, 40% (average 1.7 cm); were bilateral, 30%; and showed extrathyroidal extension, 17%. Overall, 223 (53%) patients had LNMs: 213 (51%) were central and 85 (20%) were lateral jugular. pTNM staging: I, 258 (61%); II, 35 (8%); III, 88 (21%); IV, 39 (9%). AGES (age, grade, extension, and size-thyroid tumor; and MACIS (metastasis, age, completeness of resection, invasion, and size) prognostic scores were low risk in 362 (86%) and 352 (84%), respectively. Relapse developed in 57 (14%) patients: LNM in 44, soft tissue local recurrence (LR) in 5, distant metastases (DM) in 8. Hypoparathyroidism occurred in 5 (1.2%) patients and 1 had unintentional laryngeal nerve damage. Relapse with LNM occurred in previously operated fields in 19 (5%) patients, 11(3%) from disease virulence (LR or DM), preoperative false-negative (FN) US in 12 (3%), and combination of FN-US and recurrence in the operated field in 5 (1%) patients. CONCLUSIONS: Recurrence was limited to 5% of patients when the extent of disease was accurately defined and potentially curable. This optimized surgical strategy is relatively safe.

Long-term outcome in 215 children and adolescents with papillary thyroid cancer treated during 1940 through 2008.

BACKGROUND: Controversy exists regarding the aggressiveness of initial therapy in childhood papillary thyroid cancer (PTC). Few studies with long-term outcome exist and second primary malignancies have rarely been analyzed. METHODS: We studied 215 PTC patients younger than 21 years old managed during 1940 through 2008. The patients were aged 3-20 year old (median age = 16 years); the median follow-up was 29 years. Recurrence and mortality details were taken from a computerized database. RESULTS: Median primary tumor size was 2.2 cm. Six percent had distant metastases at presentation, 5% had incomplete tumor resection, 86% had nodes removed at initial surgery, and 78% had nodal metastases. After complete surgical resection, PTC recurred in 32% by 40 years. At 20 years, the recurrence rates at local, regional, and distant sites were 7, 21, and 5%, respectively. During 1940-1969, local and regional recurrence rates after unilateral lobectomy (UL) were significantly (P < 0.001) higher than after bilateral lobar resection (BLR). During 1950-2008 radioiodine remnant ablation (RRA) was administered within 18 months to 32%; it did not diminish the 25-year regional recurrence rate of 16% seen after BLR alone (P = 0.86). Only two fatal events from PTC occurred at 28 and 30 years, for a cause-specific mortality at 40 years of only 2%. All-causes mortality rates did not exceed expectation through 20 years, but from 30 through 50 years, the number of deaths was significantly (P < 0.001) higher than predicted. Fifteen of 22 deaths (68%) resulted from nonthyroid malignancy. CONCLUSION: Survival from childhood PTC should be expected, but later death from nonthyroid malignancy is disconcerting. Seventy-three percent of those who died from nonthyroid malignancy had received postoperative therapeutic irradiation.

Laparoscopic resection of an undifferentiated pleomorphic splenic sarcoma.

BACKGROUND: Splenic tumors are rare. Malignant fibrous histiocytoma (MFH) of the spleen is one of the least common primary splenic tumors. Review of the literature shows that a laparoscopic resection has never been tried. METHOD: We discuss the case of a 76-year-old man with a 7-cm MFH in the spleen and present a review of splenic sarcomas. RESULTS: The patient underwent a successful laparoscopic splenectomy; pathology revealed a rare undifferentiated pleomorphic sarcoma of the spleen. A review of the international literature identified 15 additional cases of primary splenic MFH. Survival was rarely longer than 15 months. CONCLUSION: Malignant fibrous histiocytoma of the spleen is an exceedingly rare tumor with a poor prognosis. In experienced hands, laparoscopic splenectomy is a feasible operative choice for primary splenic sarcoma.

Thyroid cancer genetics: multiple endocrine neoplasia type 2, non-medullary familial thyroid cancer, and familial syndromes associated with thyroid cancer.

Familial thyroid cancer accounts for 25% of medullary thyroid cancer (MTC) and 5% of non-medullary thyroid cancer. All patients who have familial MTC have one of three variants of multiple endocrine neoplasia type 2 that are defined by specific mutations in the rearranged during transfection (RET) proto-oncogene. Patients who have familial nonmedullary familial thyroid cancer most likely have a mutation that is autosomal dominant with reduced penetrance. Thyroid cancer also is associated with a number of familial syndromes. This article focuses on the genetics and management of familial thyroid cancers and the syndromes associated with thyroid cancer.

Bilateral laparoscopic adrenalectomy for corticotrophin-dependent Cushing's syndrome: a review of the Mayo Clinic experience.

BACKGROUND: There has been a rapid shift from open to laparoscopic approaches in adrenal surgery, but the safety and efficacy of bilateral laparoscopic adrenalectomy (BLA) in patients with corticotrophin (ACTH)-dependent Cushing's syndrome continues to be defined. OBJECTIVE: Review outcomes in the largest series of patients reported to date undergoing BLA for ACTH-dependent Cushing's syndrome. DESIGN: Retrospective review study. PATIENTS: Between January of 1995 and October of 2006, BLA was attempted in 68 patients with ACTH-dependent Cushing's syndrome (26 ectopic ACTH syndrome; 42 persistent pituitary-dependent Cushing's syndrome following pituitary surgery). MEASUREMENTS: Review of peri-operative morbidity and mortality, biochemical parameters and patient-reported symptom response from chart review and mailed questionnaire. RESULTS: BLA was successfully completed in 59 of 68 patients (87%); nine (13%) required conversion to open adrenalectomy (OA). Intra-operative complications occurred in three patients (4.4%) (two BLA, one OA), and non-operative complications occurred in 11 (16%) patients (eight BLA, three OA). There were no peri-operative deaths. Median hospitalization was 5.5 days (range, 3-28) and 11.9 days (range, 4-29) for the BLA and OA groups, respectively. In patients with follow-up data available, all achieved biochemical resolution and at least partial clinical resolution of signs and symptoms associated with hypercortisolism. Resolution of hypertension, diabetes and obesity was achieved in 64%, 29% and 35% of patients carrying those diagnoses prior to surgery, respectively. CONCLUSIONS: This study further supports the role of BLA as an effective treatment option for patients with ACTH-dependent Cushing's syndrome.

Contralateral suppression of aldosterone at adrenal venous sampling predicts hyperkalemia following adrenalectomy for primary aldosteronism.

BACKGROUND: We aimed to determine whether a greater degree of contralateral suppression of aldosterone secretion at adrenal venous sampling predicted the development of postoperative hyperkalemia after unilateral adrenalectomy for primary aldosteronism. METHODS: A retrospective analysis of patients undergoing unilateral adrenalectomy for primary aldosteronism between 2004-2015 was performed. Clinical and biochemical parameters of patients who developed hyperkalemia (≥5.2 mmol/L) after unilateral adreanlectomy were compared with those who remained normokalemic. The contralateral suppression index was defined as the aldosterone-to-cortisol ratio from the nondominant adrenal vein divided by the aldosterone-to-cortisol ratio from the external iliac vein. RESULTS: Of 192 patients who met criteria for inclusion, 12 (6.3%) developed hyperkalemia (median serum potassium 5.5 mmol/L, range 5.2-6.2 mmol/L), with a median time to onset of 13.5 days (range 7-55 days). Five patients had transiently increased serum potassium concentrations that normalized spontaneously. Four patients received mineralocorticoid replacement therapy with fludrocortisone. On univariate analysis, hyperkalemic patients had slightly greater preoperative serum creatinine levels (1.2 vs 1.0 mg/dL, P = .01), higher postoperative creatinine (1.3 vs 1.0 mg/dL, P = .02), lesser median contralateral suppression index (0.14 vs 0.27, P = .03), and larger adenomas (1.9 vs 1.4 cm, P = .02). On multivariable logistic regression, the contralateral suppression index remained the only significant predictor of postoperative hyperkalemia (P = .04) with an optimal cut-off of <0.47. CONCLUSION: Hyperkalemia after unilateral adrenalectomy for primary aldosteronism is uncommon and usually transient, but may require mineralocorticoid supplementation. Patients with a contralateral suppression index of <0.47 require meticulous follow-up and monitoring of serum potassium concentrations after unilateral adrenalectomy.