Metabolic syndrome is associated with increased postoperative complications and use of hospital resources in patients undergoing laparoscopic adrenalectomy.

BACKGROUND: Rates of obesity and metabolic syndrome continue to rise worldwide; however, the impact of metabolic syndrome on outcomes following adrenalectomy has not been described. In this study, we sought to investigate the effects of metabolic syndrome on postoperative 30-day morbidity, mortality, and utilization of hospital resources in a large cohort of patients undergoing elective laparoscopic adrenalectomy. METHODS: Patients who underwent laparoscopic adrenalectomy from 2005 to 2014 were identified in the American College of Surgeons National Surgical Quality Improvement Program database. Patients with body mass index ≥30 kg/m2 who also had diabetes and hypertension requiring medications were defined as having metabolic syndrome. Univariate and multivariable analyses were performed for the outcomes of 30-day mortality/morbidity, major complications, and utilization of hospital resources (prolonged duration of stay ≥3 days and requirement for perioperative blood transfusion). RESULTS: Of the 3,502 patients included in the study, 395 had metabolic syndrome (11.3%). Patients with metabolic syndrome were older (P < .001) and had a greater percentage of preoperative comorbidities (P < .05) than patients without metabolic syndrome. On unadjusted analysis, metabolic syndrome was associated with an increased risk for mortality/morbidity, major complications, duration of stay, operative time, and risk for blood transfusion (all P < .001). On multivariable analysis, metabolic syndrome was an independent predictor of overall mortality/morbidity (odds ratio, 1.86; P < .001), major complications (odds ratio, 1.99; P < .001), pulmonary complications (odds ratio, 1.83; P = .049), the need for blood transfusion (odds ratio, 1.94; P = .04), and prolonged length of stay (odds ratio odds ratio, 1.34; P = .02). CONCLUSION: The presence of metabolic syndrome increased the risk for postoperative complications after laparoscopic adrenalectomy and was associated with 2-fold risk for blood transfusion and 34% increased odds of a prolonged hospital stay.

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.

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.

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.

Laparoscopic versus robotic adrenalectomy: A comprehensive meta-analysis.

BACKGROUND: The benefit of robotic adrenalectomy (RA) compared to laparoscopic adrenalectomy (LA) is still debatable. The purpose of this paper was to systematically review and synthesize all available evidence comparing RA to LA so as to evaluate which procedure provides superior clinical outcomes. METHODS: A systematic literature search of PubMed and Scopus databases was performed with respect to the PRISMA statement (end-of-search date: January 31, 2016). Data on perioperative variables were extracted by three independent reviewers. Data were pooled using a random-effects model. RESULTS: Twenty-seven studies were included in this review (13 comparative and 14 non-comparative). Overall, 1162 patients underwent adrenalectomy (747 treated with RA and 415 with LA). There was no significant difference between the robotic and the laparoscopic groups for intraoperative complications (OR: 1.20; 95%CI, 0.33-4.38), postoperative complications (OR: 0.69; 95% CI, 0.36-1.31), mortality (OR: 0.42; 95%CI, 0.07-2.72), conversion to laparotomy (OR: 0.51; 95%CI, 0.21-1.23), conversion to laparotomy or laparoscopy (OR: 0.73; 95%CI, 0.32-1.69) and blood loss (WMD: -9.78; 95%, -22.10 to 2.53). For patients treated with RA, there was a significantly shorter hospital stay (WMD: -0.40; 95% CI, -0.64 to -0.17) and a significantly longer operating time (WMD: 15.60; 95%CI, 2.12 to 29.08). CONCLUSIONS: Robotic adrenalectomy is a safe and feasible procedure with similar clinical outcomes as the laparoscopic approach in selected patient populations. High quality RCTs as well as uniform and detailed reporting of outcomes are needed to determine the role and cost-effectiveness of robotic adrenal surgery in the years to come.

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.

Adrenocortical carcinoma with inferior vena cava tumor thrombus.

BACKGROUND: The safety, efficacy, and prognostic implications of resection of adrenocortical carcinoma with inferior vena cava tumor thrombus are poorly described. METHODS: A retrospective review was performed during a 30-year period on patients who underwent resection of locally advanced, nonmetastatic adrenocortical carcinoma. We compared patients with and without inferior vena cava tumor thrombus, examining perioperative characteristics, completeness of resection, mortality, and survival. RESULTS: We identified 65 patients who underwent resection of locally advanced (T4N0 and T4N1) adrenocortical carcinoma (28 patients with inferior vena cava tumor thrombus, 37 noninferior vena cava tumor thrombus). Rate of complete resection, adjuvant chemotherapy, and short-term postoperative morbidity was similar between groups. Overall survival was similar at 12-months. At 24 months overall survival was less in the inferior vena cava tumor thrombus group (59% vs 30%, P = .04). Differential survival through 60-month follow-up favored the noninferior vena cava tumor thrombus group (36% vs 0%, P = .001). Subgroup analysis including only patients with complete resection demonstrates similar survival at 24-months but at 36-months survival favored the noninferior vena cava tumor thrombus patients (65% vs 29%, P = .047) and this continued through 60 months (40% vs 0%, P = .049). CONCLUSION: Attempt at complete resection of adrenocortical carcinoma with inferior vena cava tumor thrombus seems justified particularly as short-term safety and survival are similar to patients without inferior vena cava tumor thrombus. However, survival beyond 36-months is limited in patients with inferior vena cava tumor thrombus. Patients being evaluated for resection in the setting of inferior vena cava tumor thrombus should be selected carefully.

The role of lateral neck ultrasound in detecting single or multiple lymph nodes in papillary thyroid cancer.

BACKGROUND: Lateral neck dissection (LND) for papillary thyroid cancer (PTC) transitioned from isolated lymphadenectomy or "berry picking" based on clinical examination to multicompartment lymphadenectomy. We aimed to assess ultrasound (US) as a predictor of solitary (SLN) or multiple lymph node (MLN) metastases. METHODS: Demographics, US findings, extent of LND, and pathology were collected in patients with PTC who underwent LND. US sensitivity and specificity were calculated, and accuracy was correlated with US findings and patient characteristics. RESULTS: A total of 462 patients underwent 590 LNDs. US showed an SLN in 179 patients (30%) and MLNs in 411 patients (70%). Sensitivity, positive predictive value, and accuracy were 61%, 43%, and 75% for US detected SLN and 78%, 89%, and 75% for US detected MLNs. US accuracy for MLNs increased as node size increased (<10 mm, 63%; 10 to 20 mm, 71%; >20 mm, 89%; P < .0001). CONCLUSIONS: US has limited accuracy in the detection SLN metastasis in the lateral neck. Care should be taken when considering a focused compartment dissection.

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.

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.

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.

Teriparatide Therapy and Reduced Postoperative Hospitalization for Postsurgical Hypoparathyroidism.

IMPORTANCE: Up to 20% of patients undergoing thyroidectomy develop hypocalcemia after surgery. Although usually transient, severe symptomatic hypocalcemia may occur. Teriparatide acetate (recombinant human parathyroid hormone 1-34) therapy can rapidly raise calcium levels. OBJECTIVE: To test the hypothesis that teriparatide therapy in patients with postthyroidectomy hypoparathyroidism would expedite relief of symptomatic hypocalcemia and reduce the duration of hospitalization compared with standard treatment. DESIGN, SETTING, AND PARTICIPANTS: Case series of all hospitalized patients 18 years or older treated with teriparatide for symptomatic postthyroidectomy hypocalcemia occurring immediately after thyroidectomy at Mayo Clinic, Rochester, Minnesota, between January 1, 2008, and June 30, 2014. A secondary analysis was performed with matched control and cohort groups having postthyroidectomy hypocalcemia of similar degree who received standard treatment only. Participants included 8 hospitalized patients who received teriparatide therapy after 24 hours of standard treatment (cases) and eight control patients selected from a cohort of 1193 thyroidectomies were matched for age, sex, body mass index, and nadir calcium levels. INTERVENTION: Teriparatide acetate therapy (20 µg twice daily) subcutaneously for 1 week, with the option of continuing at 20 µg/d for up to 3 weeks. MAIN OUTCOMES AND MEASURES: Safety, symptom resolution, calcium supplementation, and duration of hospitalization. RESULTS: Among the 16 case and control patients the median nadir calcium level was 7.1 mg/dL in both groups. Most patients underwent thyroidectomy for thyroid cancer. Teriparatide therapy was safe, with no adverse events noted, and completely eliminated symptomatic hypocalcemia in all treated patients within 24 hours of initiation. Hospital discharge occurred at a median of 1.0 day (interquartile range, 1.0-1.0 day) after teriparatide therapy initiation among cases vs 2.5 days (interquartile range, 1.8-3.0 days) after the equivalent clinical point was reached in controls (P = .01). This value was 2.0 days in the source cohort (P = .02). On hospital discharge, patients had similar calcium levels. Six months after surgery, all patients treated with teriparatide showed partial or complete parathyroid recovery. Calcium supplementation and calcium levels were comparable between the groups. CONCLUSIONS AND RELEVANCE: In this pilot study, teriparatide therapy in patients with postthyroidectomy hypoparathyroidism was safe, rapidly eliminated hypocalcemic symptoms, and likely reduced the duration of hospitalization. Given the limitations of this small study, a large-scale randomized trial is needed to verify these results and to assess the long-term effect of teriparatide therapy on clinical outcomes.

Single-port robotic-assisted adrenalectomy: feasibility, safety, and cost-effectiveness.

BACKGROUND AND OBJECTIVES: The introduction of robotic surgery offers patients and surgeons new options for adrenalectomy. Whereas multiport adrenalectomies have been safely performed using the robot, we describe our experience with the novel technique of single-port robotic-assisted adrenalectomy. METHODS: We performed a matched-cohort study comparing 16 single-port robotic-assisted adrenalectomies with 16 patients from a pool of 148 laparoscopic adrenalectomies, matched for age, gender, operative side, pathology, and body mass index. All were operated on by 1 surgeon. RESULTS: The pathology included aldosteronoma in 44% of patients, adrenocorticotropic hormone-dependent Cushing syndrome (bilateral adrenalectomy) in 19%, pheochromocytoma in 13%, and other pathology in 24%. The operative time was 183 ± 33 minutes for single-port robotic-assisted adrenalectomy and 173 ± 40 minutes for laparoscopic adrenalectomy (P = .58). The total time in the operating room was 246 ± 33 minutes for single-port robotic-assisted adrenalectomy and 240 ± 39 minutes for laparoscopic adrenalectomy (P = .57). There was 1 conversion to open adrenalectomy (6%) in each group, both because of bleeding on the right side during bilateral adrenalectomy. Two right-sided single-port robotic-assisted adrenalectomy patients required conversion to laparoscopic adrenalectomy, one because of poor visualization. There were no deaths. Complications occurred in 2 patients in each group (intensive care unit admission, prolonged ileus). Both groups had similar pain scores (mean of 3.7 on a scale from 1 to 10) on postoperative day 1, and patients in the single-port robotic-assisted adrenalectomy group used less narcotic pain medication in the first 24 hours after surgery (43 mg vs 84 mg in laparoscopic adrenalectomy group, P < .001). The differences between the single-port robotic-assisted adrenalectomy group and laparoscopic adrenalectomy group in length of stay (2.3 ± 0.5 days vs 3.1 ± 0.9 days, P = .23), percentage of patients discharged on postoperative day 1 (56% vs 31%, P = .10), and hospital cost (16% lower in single-port robotic-assisted adrenalectomy group, P = .17) did not reach statistical significance. CONCLUSION: Single-port robotic adrenalectomy is feasible; patients require less narcotic pain medication whereas costs appear equivalent compared with laparoscopic adrenalectomy.

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.

Metastasectomy of neuroendocrine tumors in patients with multiple endocrine neoplasia type 1.

BACKGROUND: Neuroendocrine (NE) tumors commonly afflict patients with multiple endocrine neoplasia type 1 (MEN1). It is thought that patients with MEN1 have improved survival compared with individuals with analogous lesions. The role of metastasectomy of NE tumors in MEN1 patients is not clearly defined. METHODS: A review of MEN1 patients undergoing surgery for NE tumors from 1994 to 2010 at a single tertiary care center was performed. Tumor function, the extent of metastasis, R0 resection, and survival were analyzed. RESULTS: We identified 30 patients who underwent resection including synchronous and metachronous metastasectomy. Synchronous metastases were identified in 19 patients (63%), whereas 11 (37%) had metachronous disease. R0 resection was achieved in 93% of patients. Estimated 10-year survival is 86.4% (95% confidence interval, 60% to 100%) with no factors predictive of overall survival. The disease-free interval at 1, 5, and 10 years was 89%, 50%, and 19%, respectively, with recurrence occurring at a median of 5.4 years (95% confidence interval, 77.7% to 100%). Synchronous metastasis (P = .0072; hazard ratio [HR], 3.4) and nonfunctioning tumors (P = .014; HR, 3.3) were more likely to recur, whereas age (P = .09; HR, 1.5), gender (P = .49; HR, 1.3), and the site of metastasis (P = .81; HR, 1.1) did not influence recurrence. DISCUSSION: Patients with MEN1 benefit from resection of metastatic NE disease. Despite a high recurrence rate, survival and disease-free interval is favorable vs patients without MEN1.

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.

Operative intervention for recurrent adrenocortical cancer.

INTRODUCTION: Adrenocortical cancer (ACC) recurs despite apparent complete resection. We examined the survival and palliative benefit of resection for recurrent ACC. METHODS: A review of all patients undergoing operation for ACC between 1980 and 2010 at our institution was performed in which we compared resection with nonoperative therapy. RESULTS: Overall, 164 patients underwent operation for ACC, 125 of whom underwent a complete resection (R0). Recurrence occurred in 93 R0 patients (median, 15 months; range, 1.5-150 months). Symptoms at recurrence were present in 71% (66/93), including pain (34%) and hormone excess (43%). There were 67 patients who underwent reoperation for recurrence. Forty-eight of 67 patients underwent R0 resection for recurrence. Operative patients had a greater overall operative versus nonoperative management or no therapy (65 months vs 6 months, P < .01). Median survival for nonoperatively managed patients (226 days) and those undergoing no therapy (179 days) was less than for debulking (1,272 days, P = .002). R0 for recurrence (P = .005) and a disease-free interval >6 months (P < .001) were associated with survival after operation, whereas original tumor size (P = .47), grade (P = .8), and stage (P = .23) were not. Pain and hormonal symptoms improved in 84% of operative patients versus 29% of nonoperatively managed patients (P = .005). Debulking had similar symptomatic improvement to R0 resection (P = .52). CONCLUSION: Patients with recurrent ACC can benefit from operative intervention with improvement in survival and symptoms. Patients with a disease-free interval >6 months and complete resection are likely to benefit from resection of the recurrence, but the near universal improvement in symptoms may expand the criteria for operation in recurrent ACC.

Multiple endocrine neoplasia type 2A due to an exon 8 (G533C) mutation in a large North American kindred.

BACKGROUND: Medullary thyroid cancer, although most commonly sporadic, may be part of the multiple endocrine neoplasia type 2 (MEN2) syndromes, generally due to mutations in the RET proto-oncogene. The majority of these mutations are located in exons 10, 11, and 13-16. More rarely, mutations in other exons have been described. We report for the first time a family from the United States with a rare mutation involving exon 8 of the RET proto-oncogene, corresponding to a p.Gly533Cys substitution (G533C) leading to the development of MEN2A syndrome in several affected family members. This mutation had only been previously described in a large family in Brazil and in 7.75% of patients with apparently sporadic medullary thyroid cancer (MTC) in Greece. METHODS: Given a strong index of suspicion, a genetic analysis to evaluate for uncommon mutations in the RET proto-oncogene identified the presence of the G533C missense mutation, despite initial negative screening for common mutations. We describe a family with a total of 47 individuals from five generations with multiple members affected with this mutation. RESULTS: Our data suggest that in patients with this mutation, pheochromocytoma is more common than previously reported, and that in some cases this mutation may be associated with a more aggressive phenotype than initially described. CONCLUSIONS: MEN2A due to the G533C mutation in exon 8 may be more common and more aggressive than previously recognized. In patients with medullary thyroid cancer with negative screening for common mutations in the RET oncogene but a strong index of suspicion, DNA sequence analysis of less commonly involved exons should be considered.

Changes in bone mineral density after surgical intervention for primary hyperparathyroidism.

BACKGROUND: Patients with primary hyperparathyroidism often lack classic symptoms but can have reductions in bone mineral density and increased fracture risk. We sought to determine bone mineral density improvement after successful surgery and associated factors. METHODS: A review of patients with osteopenia or osteoporosis with curative parathyroidectomy and both pre- and postoperative dual-energy X-ray absorptiometry bone mineral density scans was conducted. We compared patients with declining (<0%), moderate improvement (0.1-5%), and significant improvement (>5%) on dual-energy X-ray absorptiometry bone mineral density scans. RESULTS: We identified 420 patients who underwent a dual-energy X-ray absorptiometry bone mineral density scan preoperatively and within 36 months postoperatively. At the most affected site, 38% had significant improvement, 31% moderate improvement, and 31% declining bone mineral density. Patients who significantly improved were younger (P = .01), had lesser preoperative dual-energy X-ray absorptiometry (P = .001), and had greater preoperative levels of parathyroid hormone (P = .04), serum calcium (P = .03), and preoperative urinary calcium. There was no difference in outcomes between sex and with preoperative bisphosphonate use. Average hip and spine bone mineral density had similar responses to surgery. CONCLUSION: Bone mineral density improves in up to 75% of patients after curative parathyroidectomy for primary hyperparathyroidism. The hip and lumbar spine responded similarly. Younger patients and those with severe primary hyperparathyroidism may derive the most skeletal benefits from parathyroidectomy, but the uniform positive response supports parathyroidectomy in patients with osteoporosis and possibly osteopenia.

Development of a multidisciplinary, multicampus subspecialty practice in endocrine cancers.

PURPOSE: Relative to more abundant neoplasms, endocrine cancers have been historically neglected, yet their incidence is increasing. We therefore sought to build interest in endocrine cancers, improve physician experience, and develop innovative approaches to treating patients with these neoplasms. METHODS: Between 2005 and 2010, we developed a multidisciplinary Endocrine Malignancies Disease Oriented Group involving all three Mayo Clinic campuses (Rochester, MN; Jacksonville, FL; and Scottsdale, AZ). In response to higher demand at the Rochester campus, we sought to develop a Subspecialty Tumor Group and an Endocrine Malignancies Tumor Clinic within the Division of Medical Oncology. RESULTS: The intended groups were successfully formed. We experienced difficulty in integration of the Mayo Scottsdale campus resulting from local uncertainty as to whether patient volumes would be sufficient to sustain the effort at that campus and difficulty in developing enthusiasm among clinicians otherwise engaged in a busy clinical practice. But these obstacles were ultimately overcome. In addition, with respect to the newly formed medical oncology subspecialty endocrine malignancies group, appointment volumes quadrupled within the first year and increased seven times within two years. The number of active therapeutic endocrine malignancies clinical trials also increased from one in 2005 to five in 2009, with all three Mayo campuses participating. CONCLUSION: The development of subspecialty tumor groups for uncommon malignancies represents an effective approach to building experience, increasing patient volumes and referrals, and fostering development of increased therapeutic options and clinical trials for patients afflicted with otherwise historically neglected cancers.