eses review of recently published literature - dgav.de · eses review of recently published...

EUROPEAN SOCIETY OF ENDOCRINE SURGEONS

ESES Review of Recently Published Literature

Collection: T. Clerici1, T. Defechereux, F. Triponez

2

Compilation and design: U. Beutner1

1: Department of Surgery, Cantonal Hospital St. Gallen, St Gallen, Switzerland

2: Department of Thoracic and Endocrine Surgery, University Hospital of Geneva, Geneva, Switzerland

[email protected]

May - Aug 2011 Data retrival from Pubmed: 3. Oct 2011

Contents click on title jumps to the according page (in Vista: CTRL-click)

Publication count: RCT SR/MA Other Page

Thyroid ............................ 2.......... 0..........80 .............................. 2

Parathyroid ..................... 0.......... 2..........42 ............................ 29

Adrenals .......................... 0.......... 2............9 ............................ 46

NET .................................. 0.......... 2..........14 ............................ 50

GI and General ................ 0.......... 0............0 ............................ 56

RCT: randomised controlled trial, SR: systematic review, MA: meta-analysis

Pubmed-ID: PubMed-Identifier (unique number for each Pubmed entry

blue underline: Hyperlink to PubMed entry or web site of publisher. Clicking on hyperlink opens the corresponding web site in browser (in Vista: CTRL-click).

ESES Review of Recently Published Literature 2011-2 of 56

Thyroid

Meta-Analyses - None -

Randomized controlled trials Randomized Clinical Trial on Harmonic Focus Shears Versus Clamp-and-Tie Technique for Total Thyroidectomy. Am J Surg, 202(2):168-74. Mourad M, Rulli F, Robert A, Scholtes JL, De MM, De PL. 2011. BACKGROUND: The Harmonic Focus is the last ultrasonic device designed for thyroid surgery. The aim is to assess its efficacy and safety compared with traditional dissection in a prospective randomized trial of total thyroidectomy procedures. METHODS: Total thyroidectomy was performed in 34 patients using the Harmonic Focus, and in 34 patients using the clamp-and-tie technique. RESULTS: In the Harmonic Focus group, relative reductions of 29% and 46% were observed in surgical time and blood loss, respectively. The number of intraoperative instrument exchanges also decreased by 70%, and use of specific materials required to achieve hemostasis decreased significantly. Safety was found to be similar in both patient groups. CONCLUSIONS: Our study showed beneficial effects of Harmonic Focus use in thyroid surgery. Further studies therefore are needed to evaluate cost in the light of savings made in surgical time, materials needed for hemostasis, and human resources. PubMed-ID: 21810497 http://dx.doi.org/10.1016/j.amjsurg.2010.07.047

Dexamethasone Prophylaxis Before Thyroidectomy to R educe Postoperative Nausea, Pain, and Vocal Dysfunction: a Randomized Clinical Controlled Trial . Head Neck, 33(6):840-6. Feroci F, Rettori M, Borrelli A, Lenzi E, Ottaviano A, Scatizzi M. 2011. BACKGROUND: The objective of this 2-arm, double-blind, randomized, controlled study was to assess the effects of a preoperative single dose steroid on postoperative nausea and vomiting (PONV), pain, and vocal function after thyroidectomy for benign disease. METHODS: We randomized 102 patients into 2 groups from January to December 2009: (1) treatment with 8 mg/2 mL of dexamethasone and (2) treatment with 2 mL NaCl 0.9%, both administered intravenously before anesthesia. RESULTS: The severity of nausea and the need for antiemetic drugs were reduced in patients receiving dexamethasone (p = .0001). Dexamethasone patients reported significantly less pain (p = .008); the need for analgesic drugs was lower in the dexamethasone group (p = .048). No differences were noted with regard to subjective voice analysis (p = .693). CONCLUSION: Dexamethasone (8 mg IV) is a safe and effective method to reduce PONV and pain after thyroid resection and should be used routinely. PubMed-ID: 20737495 http://dx.doi.org/10.1002/hed.21543

Other Articles Recalcitrant Hypocalcemia in a Lactating Woman Afte r Total Thyroidectomy for Papillary Thyroid Carcinoma. Head Neck, 33(6):920-2. Lassig AA, Donatelli PE, Teknos TN. 2011. BACKGROUND: The risk of hypocalcemia after total thyroidectomy is well-described in the literature. Recalcitrant hypocalcemia after thyroidectomy in a lactating woman is uncommon and may require multiple strategies to correct. METHODS: We present a case report of a lactating woman with papillary thyroid carcinoma requiring total thyroidectomy and neck dissections. RESULTS: Postoperatively the patient suffered from recalcitrant hypocalcemia which necessitated multiple medical maneuvers to rectify. The medical treatment required to correct the calcium levels is described herein. CONCLUSION: With the incidence of thyroid cancer on the rise and the increased identification of thyroid lesions during pregnancy, the number of lactating women undergoing thyroidectomy will likely increase. Surgeons performing thyroid surgery in this patient population should be aware of the risk of severe hypocalcemia and the tools necessary to correct it.


PubMed-ID: 20213827 http://dx.doi.org/10.1002/hed.21344

Overall and Cause-Specific Survival for Patients Un dergoing Lobectomy, Near-Total, or Total Thyroidectomy for Differentiated Thyroid Cancer. Head Neck, 33(5):645-9. Barney BM, Hitchcock YJ, Sharma P, Shrieve DC, Tward JD. 2011. BACKGROUND: The extent of surgery for well-differentiated thyroid cancer remains controversial. The purpose of this study was to evaluate the type of resection, age, T classification, nodal status, tumor size, and year of diagnosis for overall survival (OS) and cause-specific survival (CSS) using a large database. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, 23,605 subjects were identified with papillary or follicular thyroid cancer between 1983 and 2002. OS and CSS were estimated, and outcomes for local excision, lobectomy, near-total thyroidectomy, or total thyroidectomy were compared. RESULTS: Ten-year OS and CSS by surgery were: total thyroidectomy, 90.4% and 96.8%, respectively; near-total thyroidectomy, 89.5% and 96.6%, respectively; and lobectomy, 90.8% and 98.6%, respectively. Controlling for risk factors, near-total thyroidectomy was inferior to total thyroidectomy for OS (hazard ratio [HR] 1.21; p = .019) and CSS (HR 1.39; p = .019). Age, T3/T4 disease, positive nodes, and tumor size were associated with poorer outcomes. CONCLUSION: Total thyroidectomy resulted in improved survival. Therapy should be individualized, accounting for potential complications and recurrence patterns. PubMed-ID: 20687168 http://dx.doi.org/10.1002/hed.21504

Classification of Papillary Thyroid Microcarcinoma According to Size and Fine-Needle Aspiration Cytology: Behavior and Therapeutic Implications. Head Neck, 33(5):696-701. Friguglietti CU, Dutenhefner SE, Brandao LG, Kulcsar MA. 2011. BACKGROUND: The purpose of this study was to assess and classify cases of papillary microcarcinoma according to size (up to 0.5 cm and between 0.6 and 1.0 cm) and fine-needle aspiration cytology (FNAC). These results were then correlated with clinical and histopathologic factors of worse prognosis. METHODS: A total of 448 cases of papillary thyroid carcinoma were studied retrospectively. RESULTS: Of the 448 patients, 173 presented with carcinomas of </=0.5 cm and 275 patients presented with carcinomas sized between 0.6 and 1.0 cm (>0.5 cm). Lymph node metastasis was diagnosed in 6% of the carcinoma cases of </=0.5 cm and in 16% of the cases with tumors of >0.5 cm. A total of 281 cases tested positive for papillary carcinoma by FNAC, and in 113 cases, the carcinoma was diagnosed during the histopathologic examination. A positive FNAC for carcinoma was correlated with a higher incidence of lymph node metastasis (16% vs 5%). CONCLUSION: The diagnosis of papillary carcinoma using the preoperative biopsy enables a more precise oncological procedure with greater chance of biological cure. PubMed-ID: 20737499 http://dx.doi.org/10.1002/hed.21517

Aggressive Variants of Papillary Thyroid Carcinoma. Head Neck, 33(7):1052-9. Silver CE, Owen RP, Rodrigo JP, Rinaldo A, Devaney KO, Ferlito A. 2011. A number of histologic variants of well-differentiated papillary carcinoma have been found to be associated with more aggressive tumor behavior. Tall cell, columnar cell, diffuse sclerosing, solid/trabecular, and insular variants of well-differentiated papillary thyroid cancer are all potentially more aggressive than conventional papillary thyroid cancer. When subjected to multivariate analysis, however, evidence that the histologic subtype of tumor is an independent predictor of outcome is weak. Rather, the aggressive variants tend to present with features recognized by other staging systems as associated with a worse prognosis, including higher histologic grade, extracapsular spread, large tumor size, and the presence of distant metastases. Prognosis is directly related to the presence of these features. The state of our knowledge is limited by the relatively small number of cases that have been studied. The presence of an aggressive variant of papillary carcinoma should alert the surgeon that he is dealing with a potentially aggressive tumor. Clinical treatment decisions should be based on the stage of the disease, influenced by the knowledge that the aggressive variants tend to be associated with higher risk factors. The surgeon must be prepared to perform at the first, or second stage, a total thyroidectomy, central compartment neck dissection, additional lymphadenectomy, and/or resection of invaded surrounding structures, and search for distant metastasis. Postoperative radioactive iodine should generally be administered for these variants as they will generally be intermediate to advanced tumors. The tall cell variant is often refractory to such treatment but may be susceptible to treatment targeted against BRAF mutation. External beam irradiation may


be used in cases of incomplete resection. PubMed-ID: 20824810 http://dx.doi.org/10.1002/hed.21494

Multifocality in Well-Differentiated Thyroid Carcin omas Calls for Total Thyroidectomy. Am J Surg, 201(6):770-5. Mazeh H, Samet Y, Hochstein D, Mizrahi I, Ariel I, Eid A, Freund HR. 2011. BACKGROUND: Multifocality is an important factor when recommending surgery for papillary thyroid cancer (PTC). The aim of this study is to assess the incidence and characterize the spread pattern of multifocal PTC (mPTC) in patients undergoing total thyroidectomy. METHODS: All thyroidectomies performed between 2003 and 2008 were reviewed identifying 289 patients. Data were obtained for demographics, clinical data, and histopathological findings. RESULTS: Of the patients with papillary carcinoma, mPTC was identified in 150 patients (57%), of which 71% had lesions in the contralateral lobe. There were no significant differences in multifocality rate for gender, pathology type, and all tumor size subgroups including </=1 cm. Pathology examination of representative sections versus the entire gland examination resulted in a significantly lower incidence of contralateral disease (P = .04). CONCLUSIONS: Multifocal and contralateral lesions are common in PTC and their incidence is not related to tumor size. Pathology entire gland examination is strongly recommended to properly assess the rate of mPTC. PubMed-ID: 20864083 http://dx.doi.org/10.1016/j.amjsurg.2010.03.004

A Comparison of Surgical Outcomes Between Endoscopi c and Robotically Assisted Thyroidectomy: the Authors' Initial Experience. Surg Endosc, 25(5):1617-23. Lang BH, Chow MP. 2011. BACKGROUND: The gasless, transaxillary endoscopic thyroidectomy (GTET) offers a distinct advantage over the conventional open operation by leaving no visible neck scar, and in an attempt to improve its ergonomics and surgical outcomes, the robotically assisted thyroidectomy (RAT) was introduced. The RAT uses the same endoscopic route as the GTET but with the assistance of the da Vinci S robotic system. Excellent results for RAT have been reported, but it remains unclear whether RAT offers any potential benefits over GTET. METHODS: From June to December 2009, 46 patients underwent endoscopic thyroidectomy. Of these patients, 39 had surgery without the robot (GTET) and 7 had surgery with the robot (RAT). Demographics, surgical indications, operative findings, and postoperative outcomes were compared between the two groups. All the patients were followed up for at least 6 months after surgery. RESULTS: Patient demographics, surgical indications, and extent of resection were similar between the two groups. The median total procedure time was significantly longer for RAT (149 min) than for GTET (100 min; p=0.018), but the contralateral recurrent laryngeal nerve was more likely to identified in RAT (100%) than in GTET (42.9%; p=0.070). On the average, GTET needed one more surgical assistant than RAT (1 vs. 0; p<0.001). The median pain score on postoperative day 0 was significantly higher with RAT than with GTET (4 vs. 2; p=0.025) but was similar on day 1. Blood loss, hospital stay, and surgical complications were similar in the two groups. CONCLUSIONS: In our early experience, adding the da Vinci S robot to GTET increased the total procedure time and resulted in a higher pain score on day 0 but eliminated the need for any surgical assistant at the time of the operation. PubMed-ID: 21088857 http://dx.doi.org/10.1007/s00464-010-1450-y

Central Compartment Reoperation for Recurrent/Persi stent Differentiated Thyroid Cancer: Patterns of Recurrence, Morbidity, and Prediction of Postoperat ive Hypocalcemia. Ann Surg Oncol, 18(5):1312-8. Roh JL, Kim JM, Park CI. 2011. BACKGROUND: Incidence rates of hypoparathyroidism and vocal cord paralysis are high following central compartment reoperation, but few prospective studies have assessed morbidities and factors predictive of hypocalcemia after reoperation. We investigated recurrence patterns, morbidity, and factors predictive of postoperative hypocalcemia in patients undergoing central compartment reoperation for recurrent/persistent differentiated thyroid cancer (DTC). METHODS: We prospectively evaluated 45 consecutive patients with recurrent/persistent DTC. Thyroid remnants or recurrent cancers were removed in 16 patients, the unilateral or bilateral central compartment was cleared in all patients, and the lateral compartment on the diseased side was comprehensively removed from 24 patients. Recurrence patterns were assessed histopathologically, morbidities were monitored, and serum concentrations of calcium and intact parathyroid hormone (iPTH) were measured in all patients. RESULTS: Eleven patients (24.4%) had tumor invasion into the recurrent laryngeal nerve and/or the


tracheoesophagus. Central nodal involvement occurred frequently (86.7%), and the ipsilateral jugular nodes of the lateral compartment were frequently involved. Temporary and permanent vocal cord paralysis developed in 10 (22.2%) and 8 (17.8%) patients, respectively, due primarily to intentional nerve resection following tumor invasion. Of 41 patients without preoperative hypoparathyroidism, 21 (46.3%) had temporary and 2 (4.9%) had permanent hypocalcemia. Multivariate analysis showed that bilateral central compartment dissection and low iPTH levels (<12.0 pg/ml) were independent predictors of postoperative hypocalcemia. CONCLUSIONS: Most patients with recurrent/persistent DTC harbor lesions in the central compartment. Central compartment reoperation may lead to high rates of morbidity, including hypoparathyroidism, which can be predicted by surgical extent and low serum iPTH levels. PubMed-ID: 21140230 http://dx.doi.org/10.1245/s10434-010-1470-9

Characteristics of Primary Papillary Thyroid Carcin oma With False-Negative Findings on Initial (18)F-FDG PET/CT. Ann Surg Oncol, 18(5):1306-11. Choi JW, Yoon YH, Yoon YH, Kim SM, Koo BS. 2011. BACKGROUND: We often observe that uptake of tracer is not detected in the primary cancer focus in patients with histologically proven papillary thyroid carcinoma (PTC) on preoperative (18)F-fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG PET/CT). Therefore, we analyzed the clinical and pathologic variables affecting false-negative findings in primary tumors on preoperative (18)F-FDG PET/CT. METHODS: We retrospectively reviewed the medical records of 115 consecutive patients who underwent (18)F-FDG PET/CT for initial evaluation and were diagnosed with PTC by postoperative permanent biopsy. The clinical and pathologic characteristics that influence the (18)F-FDG PET/CT findings in these patients were analyzed with respect to the following variables: age, gender, tumor size, multifocality of the primary tumor, perithyroidal invasion, lymphovascular or capsular invasion, and central lymph node metastasis-based final pathology. RESULTS: Twenty-six (22.6%) patients had false-negative (18)F-FDG PET/CT findings. In patients with negative (18)F-FDG PET/CT findings, tumor size, and perithyroidal and lymphovascular invasion were significantly less than in patients with positive (18)F-FDG PET/CT findings. Tumors >1 cm in size were correlated with (18)F-FDG PET/CT positivity. On multivariate analysis, perithyroidal invasion (P = 0.026, odds ratio = 7.714) and lymphovascular invasion (P = 0.036, odds ratio = 3.500) were independent factors for (18)F-FDG PET/CT positivity. However, there were no significant differences between (18)F-FDG PET/CT positivity and age, gender, capsular invasion, and central lymph node metastasis based on final pathology. CONCLUSIONS: Tumor size and perithyroidal and lymphovascular invasion of papillary carcinoma can influence (18)F-FDG PET/CT findings. Absence of perithyroidal and lymphovascular invasion were independent variables for false-negative findings on initial (18)F-FDG PET/CT in patients with PTC. PubMed-ID: 21140231 http://dx.doi.org/10.1245/s10434-010-1469-2

Effect of Smoking on Orbital Fat and Muscle Volume in Graves' Orbitopathy. Thyroid, 21(2):177-81. Regensburg NI, Wiersinga WM, Berendschot TT, Saeed P, Mourits MP. 2011. BACKGROUND: Smoking adversely affects the course and severity of Graves' orbitopathy (GO). Cigarette smoke enhances adipogenesis in cultured human orbital fibroblasts. The present study tested our hypothesis that smoking is associated with increased orbital fat in GO patients. METHODS: This was an observational case series study. In 95 consecutive patients with untreated GO, the ratios of fat volume/orbital volume (FV/OV) and muscle volume/OV (MV/OV) were calculated with validated software. The most affected orbit of each patient was chosen for analysis. Patients were divided into two groups based on smoking behavior. One group was current smokers (Sm+) and the other were those who never smoked or those who had not smoked for at least 1 year (Sm-). Patients were grouped in tertiles of FV/OV and MV/OV and contrast in OVs between the Sm+ and Sm- group. The main characteristics of GO were analyzed using Jonckheere-Terpstra trend analysis and Mann-Whitney U-test. RESULTS: The proportion of current smokers was not different in GO patients when divided in tertiles according to their FV/OV. In contrast, analysis of MV/OV tertiles showed a trend to a higher prevalence of current smokers in patients with larger MVs. Smoking did not influence FV, but the Sm+ group had significantly larger MVs than the Sm- group. CONCLUSION: Smoking is associated with an increase in extraocular MV in untreated patients with GO and not with an increase in FV. PubMed-ID: 21142817 http://dx.doi.org/10.1089/thy.2010.0218


Elastic Light-Scattering Spectroscopy for Discrimin ation of Benign From Malignant Disease in Thyroid Nodules. Ann Surg Oncol, 18(5):1300-5. Suh H, A'amar O, Rodriguez-Diaz E, Lee S, Bigio I, Rosen JE. 2011. BACKGROUND: Thyroid cancer is the most common endocrine malignancy. The current standard of diagnosis, fine-needle aspiration biopsy, yields approximately 10-25% of indeterminate results leading to twice as many thyroidectomies for further diagnosis. Elastic scattering spectroscopy (ESS) is a new, minimally invasive optical-biopsy technique mediated by fiber-optic probes that is sensitive to cellular and subcellular morphological features. We assessed the diagnostic potential of ESS in the thyroid to differentiate benign from malignant thyroid nodules as determined by histology. METHODS: Under an IRB approved protocol, 36 surgical patients (n = 21 benign thyroid nodules, n = 15 malignant tumors) had collection of ESS data from their fresh ex vivo thyroidectomy specimens. Using surgical pathology as our gold standard, spectral analyses were performed using a training set; these data were used to assess the ESS diagnostic potential using the leave-one-out technique. RESULTS: Our test set was 75% sensitive and 95% specific in differentiating benign from malignant thyroid lesions, with a positive predictive value (PPV) of 0.92 and a negative predictive value (NPV) of 0.83. CONCLUSIONS: The ESS can accurately distinguish benign vs malignant thyroid lesions with high PPV and NPV. With further validation ESS could potentially be used as an in situ real-time diagnostic tool or as an adjunct to conventional cytology. PubMed-ID: 21174158 http://dx.doi.org/10.1245/s10434-010-1452-y

Surveillance and Intervention After Thyroid Lobecto my. Ann Surg Oncol, 18(6):1729-33. Spanheimer PM, Sugg SL, Lal G, Howe JR, Weigel RJ. 2011. BACKGROUND: After thyroid lobectomy, many patients require ongoing care. This study sought to quantify the rates of surveillance and intervention after thyroid lobectomy. METHODS: One hundred one consecutive patients who underwent a thyroid lobectomy for nodular disease were evaluated. Clinical and follow-up data were obtained by a review of patient charts and included an evaluation of resource utilization related to thyroid disease. RESULTS: Nineteen patients required completion thyroidectomy for thyroid cancer, and 11 had hypothyroidism before lobectomy. Of the remaining evaluable patients, 30 (42.2%) of 71 required thyroid hormone replacement after lobectomy, with 24 patients having elevated thyroid-stimulating hormone and 6 suppression of nodules in the contralateral lobe. The likelihood of thyroid hormone replacement demonstrated a trend with a contralateral nodule (9 of 14 vs. 21 of 57, P = 0.06) and a significant association with thyroiditis on surgical pathology (10 of 11 vs. 20 of 60, P < 0.001). Of the 82 patients who did not undergo completion lobectomy, 10 (12%) of 82 underwent postoperative fine-needle aspiration of the contralateral lobe, and 25 (30%) of 82 were followed with ultrasound surveillance. Only 27% of patients treated with lobectomy required no further surveillance or intervention. There were no instances of permanent recurrent laryngeal nerve injury. CONCLUSIONS: After thyroid lobectomy, most patients require continued surveillance and intervention. With a near-zero complication rate, total thyroidectomy may be a more effective and efficient option for management of nodular thyroid disease. PubMed-ID: 21246403 http://dx.doi.org/10.1245/s10434-010-1544-8

Minimal Extrathyroidal Extension in Patients With P apillary Thyroid Microcarcinoma: Is It a Real Prognostic Factor? Ann Surg Oncol, 18(7):1916-23. Moon HJ, Kim EK, Chung WY, Yoon JH, Kwak JY. 2011. BACKGROUND: The clinical impact of minimal extrathyroidal extension (ETE) in patients with conventional papillary thyroid microcarcinoma (PTMC) is still controversial. The clinicopathologic characteristics of patients with or without minimal ETE or recurrence and the clinical impact of minimal ETE were investigated. METHODS: This study included 288 patients with conventional PTMC (mean age, 46.6 years; 262 female and 26 male subjects) and more than 5 years of follow-up. Patients were divided into two groups according to ETE and recurrence, and clinicopathologic characteristics between two groups were investigated. Disease-free survival was calculated to compare the clinical impact of minimal ETE between patients with and without ETE. RESULTS: Mean size (6.9 mm) of PTMCs in patients with minimal ETE (n = 89) was significantly larger than that in those (5.8 mm) without (n = 199) (P < 0.001). Tumor size [odds ratio (OR) = 1.185; 95% confidence interval (CI) 1.052-1.334], central lymph node (LN) metastasis at diagnosis (OR 2.105; 95% CI 1.182-3.750), and not well-defined margin on ultrasound (OR 3.808; 95% CI 1.055-13.736) were significantly associated with minimal ETE. Twelve patients (4.2%) had recurrence. No clinicopathologic factor was associated with recurrence.


Disease-free survival was not significantly different between patients with and without minimal ETE (P = 0.671). CONCLUSIONS: Minimal ETE was statistically significantly associated with tumor size, central LN metastasis, and not well-defined margin on ultrasound. Minimal ETE had no impact on recurrence in patients with conventional PTMC. PubMed-ID: 21267788 http://dx.doi.org/10.1245/s10434-011-1556-z

The Concepts in Poorly Differentiated Carcinoma of the Thyroid: a Review Article. J Surg Oncol, 103(8):818-21. Nambiar A, Pv S, Susheelan V, Kuriakose MA. 2011. Poorly differentiated carcinomas of the thyroid have evolved over the past half century into a specific entity in the classification of thyroid carcinomas. The need for a consensus diagnostic criteria has been stressed in view of the wide discrepancies and confusion among pathologists and clinicians. This review attempts to understand the concept, the evolution, clarity and validity of the concepts in poorly differentiated carcinomas of the thyroid. PubMed-ID: 21283991 http://dx.doi.org/10.1002/jso.21803

Does Previous Head and Neck Irradiation Increase th e Chance of Multigland Disease in Patients With Hyperparathyroidism? Ann Surg Oncol, 18(8):2240-4. Woll M, Sippel RS, Chen H. 2011. BACKGROUND: Exposure to therapeutic radiation, whether used to treat lymphoma, breast cancer, or benign conditions, such as acne, is thought to cause an increased risk for thyroid and/or parathyroid neoplasia. We therefore investigated whether patients with a history of head/neck irradiation and hyperparathyroidism (HPT) had a higher incidence of multigland disease. METHODS: Between November 2000 and May 2010, 1,428 patients with HPT underwent parathyroidectomy at our institution. Of these cases, 39 patients (2.7%) had a history of radiation exposure (RADRX). These 39 cases were compared with the 1,389 cases without prior exposure (NO RAD RX). RESULTS: There were no significant differences in gender or age between the two groups. Whereas most laboratory values were similar, preoperative parathyroid hormone levels were higher in the NO RADRX patients (174 +/- 7 vs. 106 +/- 8 pg/ml; P < 0.001). Interestingly, the resected parathyroid glands were significantly smaller in the RADRX group compared with the NO RADRX group (511 +/- 70 vs. 790 +/- 37 mg; P = 0.001). No differences were noted in the recurrence rate (P = 0.392). Contrary to common belief, RADRX patients did not have a significantly higher incidence of multigland disease (P = 0.774). Of the 39 RADRX patients, 12 (31%) had multigland disease, whereas 398 of the 1,389 (28%) NO RADRX patients had multigland disease. CONCLUSIONS: Surgical outcomes are excellent in patients with a previous history of radiation and HPT who undergo parathyroidectomy. Previous radiation exposure does not appear to increase the likelihood of multigland disease in patients with HPT. PubMed-ID: 21301971 http://dx.doi.org/10.1245/s10434-011-1579-5

High Prevalence of RAS Mutations in RET-Negative Sp oradic Medullary Thyroid Carcinomas. J Clin Endocrinol Metab, 96(5):E863-E868. Moura MM, Cavaco BM, Pinto AE, Leite V. 2011. CONTEXT: Sporadic medullary thyroid carcinomas (MTC) frequently harbor mutations in the RET protooncogene. We have earlier reported a series of 51 sporadic MTC with 64.7% of RET-positive and 35.3% of RET-negative cases. OBJECTIVE: In the present study, we investigated the possible involvement of RAS and BRAF protooncogenes in the development of sporadic RET-negative MTC. PATIENTS AND DESIGN: We performed PCR amplification and sequencing analysis of the three mutational hotspots (codons 12, 13, and 61) of the H-, K-, and N-RAS genes, and of the mutational hotspot (codon 600) and exon 11 of the BRAF gene in 65 sporadic MTC, of which 40 were RET positive and 25 were RET negative. RESULTS: Somatic H-RAS and K-RAS mutations were detected in 14 of 25 (56.0%) and three of 25 (12.0%) of RET-negative sporadic MTC, respectively. On the other hand, only one of 40 (2.5%) RET-positive sporadic MTC had a RAS mutation, namely in H-RAS. One of the H-RAS mutations was novel (c.32_37dupCCGGCG). No mutations of N-RAS or BRAF were detected in all assessed tumor samples. CONCLUSIONS: Overall, our results showed that RAS mutations were present in 68.0% (17 of 25) of the RET-negative MTC and in only 2.5% of the RET-positive MTC (P < 0.0001), suggesting that activation of the protooncogenes RAS and RET represents alternative genetic events in sporadic MTC tumorigenesis. PubMed-ID: 21325462 http://dx.doi.org/10.1210/jc.2010-1921


Inadequate Cytology of Thyroid Nodules. Repeat It o r Live With It. Ann Surg Oncol, 18(5):1222-3. Jaume JC, Chen H. 2011. PubMed-ID: 21327821 http://dx.doi.org/10.1245/s10434-011-1606-6

Does Mediastinal Extension of the Goiter Increase M orbidity of Total Thyroidectomy? A Multicenter Study of 19,662 Patients. Ann Surg Oncol, 18(8):2251-9. Testini M, Gurrado A, Avenia N, Bellantone R, Biondi A, Brazzarola P, Calzolari F, Cavallaro G, De TG, Guida P, Lissidini G, Loizzi M, Lombardi CP, Piccinni G, Portincasa P, Rosato L, Sartori N, Zugni C, Basile F. 2011. PURPOSE: To compare the outcome in patients with cervical goiters and cervicomediastinal goiters (CMGs) undergoing total thyroidectomy using the cervical or extracervical approach. METHODS: This was a retrospective study conducted at six academic departments of general surgery and one endocrine-surgical unit in Italy. The study population consisted of 19,662 patients undergoing total thyroidectomy between 1999 and 2008, of whom 18,607 had cervical goiter (group A) and 1055 had CMG treated using a cervical approach (group B, n = 986) or manubriotomy (group C, n = 69). The main parameters of interest were symptoms, gender, age, operative time, duration of drain, length of hospital stay, malignancy and outcome. RESULTS: A split-sternal approach was required in 6.5% of cases of CMG. Malignancy was significantly more frequent in group B (22.4%) and group C (36.2%) versus group A (10.4%; both P < .001), and in group C versus group B (P = .009). Overall morbidity was significantly higher in groups B + C (35%), B (34.4%) and C (53.5%) versus group A (23.7%; P < .001). Statistically significant increases for group B + C versus group A were observed for transient hypocalcemia, permanent hypocalcemia, transient recurrent laryngeal nerve (RLN) palsies, permanent RLN palsies, phrenic nerve palsy, seroma/hematoma, and complications classified as other. With the exception of transient bilateral RLN palsy, all of these significant differences between group B + C versus group A were also observed for group B versus group A. CONCLUSIONS: Symptoms, malignancy, overall morbidity, hypoparathyroidism, RLN palsy and hematoma are increased in cases of substernal goiter. PubMed-ID: 21336513 http://dx.doi.org/10.1245/s10434-011-1596-4

Clinical Review: Incidentally Discovered Medullary Thyroid Cancer: Diagnostic Strategies and Treatment. J Clin Endocrinol Metab, 96(5):1237-45. Ahmed SR, Ball DW. 2011. CONTEXT: Medullary thyroid carcinoma (MTC) is diagnosed only after thyroidectomy in approximately 10-15% of cases. This delay in diagnosis can have adverse consequences such as missing underlying pheochromocytoma or hyperparathyroidism in unrecognized multiple endocrine neoplasia type 2 and choosing a suboptimal extent of surgery. Barriers to accurate preoperative diagnosis and management strategies after the discovery of occult MTC are reviewed. EVIDENCE ACQUISITION: We reviewed PubMed (1975-September 2010) using the search terms medullary carcinoma, calcitonin, multinodular goiter, Graves' disease, calcium/diagnostic use, and pentagastrin/diagnostic use. EVIDENCE SYNTHESIS: The combined prevalence of occult MTC in thyroidectomy series is approximately 0.3%. Routine calcitonin measurement in goiter patients identifies C-cell hyperplasia as well as MTC. Challenges include interpreting intermediate values and unavailability of pentagastrin stimulation testing in the United States. Early studies have begun to identify appropriate cutoff values for calcium-stimulated calcitonin. For management of incidentally discovered MTC, we highlight the role of early measurement of calcitonin and carcinoembryonic antigen, RET testing, and comprehensive neck ultrasound exam to direct further imaging, completion thyroidectomy, and lymph node dissection. CONCLUSIONS: Occult MTC is an uncommon, but clinically significant entity. If calcium stimulation testing cutoff data become well-validated, calcitonin screening would likely become more widely accepted in the diagnostic work-up for thyroid nodules in the United States. Among patients with incidental MTC, those with persistently elevated serum calcitonin levels, positive RET test, or nodal disease are good candidates for completion thyroidectomy and lymph node dissection in selected cases, whereas patients with undetectable calcitonin, negative RET testing, and no sonographic abnormalities often may be watched conservatively. PubMed-ID: 21346073 http://dx.doi.org/10.1210/jc.2010-2359

Thyroid Nodule Guidelines: Agreement, Disagreement and Need for Future Research. Nat Rev Endocrinol, 7(6):354-61. Paschke R, Hegedus L, Alexander E, Valcavi R, Papini E, Gharib H. 2011.


This article reviews agreement, disagreement and need for future research of the thyroid nodule guidelines published by the British Thyroid Association, National Cancer Institute, American Thyroid Association and the joint, transatlantic effort of three large societies, the American Society of Clinical Endocrinologists, Associazione Medici Endocrinologi and the European Thyroid Association, published in 2010. Consensus exists for most topics in the various guidelines. A few areas of disagreement, such as the use of scintigraphy, are mostly due to differences in disease prevalence in different countries. Most of the discordance, for example, on the use of calcitonin screening or fine-needle aspiration cytology classification, could probably be resolved by further expert discussions, as the basis is the same published evidence. Importantly, owing to a current lack of evidence in many areas, clinically very relevant areas of uncertainty need to be addressed by further research. This situation applies, for instance, to better definition of ultrasound malignancy criteria and the evaluation of emerging new diagnostic and therapeutic techniques, including molecular markers. For clinicians who advise individual patients, these areas of uncertainty can currently only be resolved by sound management on the basis of clinical judgment, experience and patient preference. PubMed-ID: 21364517 http://dx.doi.org/10.1038/nrendo.2011.1

Long-Term Follow-Up of Patients With Papillary and Follicular Thyroid Cancer: a Prospective Study on 715 Patients. J Clin Endocrinol Metab, 96(5):1352-9. Brassard M, Borget I, Edet-Sanson A, Giraudet AL, Mundler O, Toubeau M, Bonichon F, Borson-Chazot F, Leenhardt L, Schvartz C, Dejax C, Brenot-Rossi I, Toubert ME, Torlontano M, Benhamou E, Schlumberger M. 2011. PURPOSE: This prospective study evaluated the recurrence rate in 715 patients with differentiated thyroid cancer who had no evidence of persistent disease after total thyroidectomy and lymph node dissection in 94% of them followed up by radioiodine ablation (30-100 mCi) and assessed the predictive value of the initial thyroglobulin (Tg) levels for detecting recurrence, both during levothyroxine (LT4) treatment and after TSH stimulation. PATIENTS AND METHODS: Patients had Tg determinations performed at 3 months on LT4 treatment (Tg1) and at 9-12 months after stimulation by either thyroid hormone withdrawal or recombinant human TSH (Tg2); the Access kit was used (functional sensitivity of 0.11 ng/ml); they had undetectable anti-Tg antibodies. Patients were followed up annually. Predictive values were calculated by comparing Tg levels (Tg1 and Tg2) and the outcome in terms of recurrence. RESULTS: During the median follow-up of 6.2 yr, 32 patients had a recurrence. Assuming a cutoff level for Tg1 at 0.27 ng/ml, Tg1 sensitivity and specificity reached 72 and 86%, respectively, whereas predictive positive and negative values were 20 and 99%, respectively. With a cutoff level for Tg2 at 1.4 ng/ml, sensitivity and specificity reached 78 and 90%, respectively, whereas positive and negative predictive values were 26 and 99%, respectively. CONCLUSION: This large prospective cohort of patients presented a low rate of recurrence. Initial Tg measurements allow to predict long-term recurrence with an excellent specificity. Stimulated Tg determination presented a slightly higher sensitivity than Tg determination on LT4. TSH stimulation may be avoided when Tg measured 3 months after ablation is less than 0.27 ng/ml during LT4 treatment. PubMed-ID: 21389143 http://dx.doi.org/10.1210/jc.2010-2708

Latencies Shorter Than 3.5 Ms After Vagus Nerve Sti mulation Signify a Nonrecurrent Inferior Laryngeal Nerve Before Dissection. Ann Surg, 253(6):1172-7. Brauckhoff M, Machens A, Sekulla C, Lorenz K, Dralle H. 2011. OBJECTIVE: Quantitative electromyographic signals recorded after vagus nerve stimulation during intraoperative neuromonitoring (IONM) were analyzed for their clinical usefulness to identify and track a nonrecurrent inferior laryngeal nerve (NRLN) before dissection. BACKGROUND: A NRLN is anatomically shorter than a recurrent inferior laryngeal nerve (RLN). This disparity should cause differential latencies after vagus nerve stimulation during IONM, which may aid in distinguishing a NRLN from a RLN. Failure to identify a NRLN early on entails a great risk of nerve injury. METHODS: Included in this IONM case-control study were 18 cases with a NRLN and 36 controls with RLN anatomy matched for gender, age, body size, and underlying thyroid and parathyroid disease. RESULTS: All 18 NRLN were found in the right neck only. Cases with a NRLN had significantly shorter latencies than controls (medians of 2.7 vs. 4.6 ms; P < 0.001) but comparable amplitude and duration after stimulation of the right vagus nerve. With a latency threshold of <3.5 ms, sensitivity, specificity, positive and negative predictive value, and accuracy, respectively, were 100%, 94%, 100%, 97%, and 98% for diagnosis of a NRLN. CONCLUSIONS: A latency threshold of 3.5 ms after ipsilateral vagus nerve stimulation during IONM was able to discriminate well between a NRLN and a RLN in adults, helping avoid injury to the


aberrant nerve. Additional studies should explore latency thresholds in children and adolescents who have shorter inferior laryngeal nerves and conceivably shorter latencies than adults. PubMed-ID: 21394011 http://dx.doi.org/10.1097/SLA.0b013e3182128b9e

German Association of Endocrine Surgeons Practice G uidelines for the Surgical Treatment of Benign Thyroid Disease. Langenbecks Arch Surg, 396(5):639-49. Musholt TJ, Clerici T, Dralle H, Frilling A, Goretzki PE, Hermann MM, Kussmann J, Lorenz K, Nies C, Schabram J, Schabram P, Scheuba C, Simon D, Steinmuller T, Trupka AW, Wahl RA, Zielke A, Bockisch A, Karges W, Luster M, Schmid KW. 2011. INTRODUCTION: Benign thyroid disorders are among the most common diseases in Germany, affecting around 15 million people and leading to more than 100,000 thyroid surgeries per year. Since the first German guidelines for the surgical treatment of benign goiter were published in 1998, abundant new information has become available, significantly shifting surgical strategy towards more radical interventions. Additionally, minimally invasive techniques have been developed and gained wide usage. These circumstances demanded a revision of the guidelines. METHODS: Based on a review of relevant recent guidelines from other groups and additional literature, unpublished data, and clinical experience, the German Association of Endocrine Surgeons formulated new recommendations on the surgical treatment of benign thyroid diseases. These guidelines were developed through a formal expert consensus process and in collaboration with the German societies of Nuclear Medicine, Endocrinology, Pathology, and Phoniatrics & Pedaudiology as well as two patient organizations. Consensus was achieved through several moderated conferences of surgical experts and representatives of the collaborating medical societies and patient organizations. RESULTS: The revised guidelines for the surgical treatment of benign thyroid diseases include recommendations regarding the preoperative assessment necessary to determine when surgery is indicated. Recommendations regarding the extent of resection, surgical techniques, and perioperative management are also given in order to optimize patient outcomes. CONCLUSIONS: Evidence-based recommendations for the surgical treatment of benign thyroid diseases have been created to aid the surgeon and to support optimal patient care, based on current knowledge. These recommendations comply with the Association of the Scientific Medical Societies in Germany requirements for S2k guidelines. PubMed-ID: 21424798 http://dx.doi.org/10.1007/s00423-011-0774-y

Incidental Papillary Microcarcinoma of the Thyroid- Further Evidence of a Very Low Malignant Potential: A Retrospective Clinicopathological Study With Up t o 30 Years of Follow-Up. Ann Surg Oncol, Neuhold N, Schultheis A, Hermann M, Krotla G, Koperek O, Birner P. 2011. BACKGROUND: Despite the frequent occurrence of papillary microcarcinoma (PMC) of the thyroid, no consensus on its malignant potential or its treatment exists. The objective of this study was to analyze the clinicopathological characteristics of a retrospective cohort of consecutive patients with PMC treated in a single institution during a 30-year period and to study the incidence rates of PMC in all patients operated on for thyroid diseases during this period. METHODS: Demographic data, clinical characteristics, histological workup of the resected glands, histopathological features, treatment, and follow-up data were studied. RESULTS: Between 1975 and 1994, 759 PMCs were detected in 28,197 patients who received thyroidal surgery. The detection rate of PMC was significantly determined by the accuracy of the histological examination. Only 5 patients with PMC presented with clinically apparent lymph node metastases and 754 were incidental PMCs. Mean follow-up was 88 +/- 2 (range, 11-639) months. Only three patients experienced recurrence in cervical lymph nodes, all of whom presented with clinically suspect cervical nodes. No patient died of disease. Clinically apparent lymph node metastases and stage pT3 were significantly associated with recurrence. CONCLUSIONS: Incidentally detected PMC, even when multifocal, is a biologically indolent tumor that seldom if ever progresses. In contrast, clinically occult PMC detected due to clinically suspected and histological confirmed lymph node metastases or extrathyroidal growth may show a more aggressive course with disease recurrence and an eventual poorer prognosis. PubMed-ID: 21431405 http://dx.doi.org/10.1245/s10434-011-1663-x

Risk-Adapted Management of Differentiated Thyroid C ancer Assessed by a Sensitive Measurement of Basal Serum Thyroglobulin. J Clin Endocrinol Metab, 96(6):1703-9. Malandrino P, Latina A, Marescalco S, Spadaro A, Regalbuto C, Fulco RA, Scollo C, Vigneri R, Pellegriti G.


2011. CONTEXT: Treatment and follow-up of patients thyroidectomized for differentiated thyroid carcinoma (DTC) mainly depends on the identification of the patient's risk of recurrence. Thyroglobulin (Tg) is the most important marker of persistent/recurrent disease. The recent introduction of a new, more sensitive Tg measurement allows for the early detection of the disease by measuring the basal (under L-T(4) therapy) serum Tg level without TSH stimulation. OBJECTIVE: The goal of this study is to identify the basal serum Tg threshold value that indicates recurrent disease by using a second-generation Tg assay. DESIGN AND PATIENTS: A continuous series of 425 DTC patients, all thyroidectomized and treated with (131)I after surgery and having basal Tg of no more than 1.0 ng/ml, negative anti-Tg antibodies, and a recombinant human TSH-stimulated Tg measurement was retrospectively analyzed. SETTING: The study took place at an academic hospital. RESULTS: The most accurate basal Tg value for predicting the presence of recurrent/residual disease was more than 0.15 ng/ml (sensitivity 87%, specificity 91%, negative predictive value 98.6%, and positive predictive value 47.8%). When the basal Tg level was no more than 0.15 ng/ml, the risk of disease presence was very low, even in patients classified at an intermediate or high risk. In contrast, when the basal Tg level was more than 0.15 ng/ml, the percentage of recurrent disease was relatively high (12.5% or one in eight cases) in low-risk patients. CONCLUSIONS: Basal Tg, measured using a second-generation Tg assay allows for the identification of DTC patients who are likely to remain disease free with great accuracy. This simple measurement, therefore, may be sufficient to assess the risk-adapted management of DTC patients. PubMed-ID: 21450986 http://dx.doi.org/10.1210/jc.2010-2695

Endoscopic Minimally Invasive Thyroidectomy (EMIT): Safety First! World J Surg, 35(8):1936-7. Benhidjeb T, Stark M. 2011. PubMed-ID: 21472370 http://dx.doi.org/10.1007/s00268-011-1077-8

Disease-Related Death in Patients Who Were Consider ed Free of Macroscopic Disease After Initial Treatment of Well-Differentiated Thyroid Carcinoma. Thyroid, 21(5):501-4. Nixon IJ, Ganly I, Palmer FL, Whitcher MM, Patel SG, Tuttle RM, Shaha AR, Shah JP. 2011. Background: Death from well-differentiated thyroid cancer (WDTC) is rare, and over the past century there has been a trend away from local recurrence as the primary cause of death. The objective of our study was to report the cause of death from thyroid cancer in patients with WDTC treated with curative intent with surgery +/- adjuvant radioactive iodine. Methods: An institutional database of 1811 patients with WDTC treated surgically for WDTC between 1986 and 2005 was analyzed and identified 165 (9.4%) who had died. Case records were studied to determine the cause of death in each patient. Results: Of the 165 deaths, 17 (10%) patients were confirmed to have died of thyroid cancer and 6 (4%) died of an unknown cause but had thyroid cancer present at the time of last follow-up. The remaining 142 (86%) died from other causes and were considered free of thyroid cancer at their last follow-up. We therefore identified only 23 cause-specific deaths from the entire cohort (1.3%). Of the 17 patients known to have died of thyroid cancer, all had distant recurrence. Ninety-four percent had pulmonary metastases. Of these, 47% also had bony metastasis at the time of death. Two patients had recurrent disease in the neck at the time of death, but both also had distant disease. Of the six patients (4%) who died of unknown causes but had thyroid cancer at last follow-up, four (67%) had distant disease alone, one (17%) had local and regional recurrence, and one had local and distant recurrence at last follow-up. Conclusion: After successful resection of WDTC, we report a low disease-specific death rate (1.3%). In contrast to earlier reports, death caused by central compartment disease in this recent series is very rare, with metastatic disease accounting for almost all fatalities. PubMed-ID: 21476889 http://dx.doi.org/10.1089/thy.2010.0451

Chylothorax Associated With Substernal Goiter Treat ed With Transcervical Thyroidectomy. Thyroid, 21(5):551-3. Hunt JP, Wilson M, Buchmann LO. 2011. Background: Substernal goiters are frequently associated with compressive symptoms. Compression of the trachea and esophagus are common, whereas thoracic duct compression is a rare occurrence. Methods: We report a rare case of a 72-year-old woman with thoracic duct compression by a large substernal goiter that presented with shortness of breath. After undergoing thoracentesis multiple times, the patient was treated with thyroidectomy. Results: Transcervical thyroidectomy was performed without sternotomy. This led to resolution of


her symptoms. Confirmation of chylothorax resolution was obtained with postoperative computed tomography of the chest. Conclusion: Chylothorax is a rare sequela of substernal goiters. It can be managed with thyroidectomy. Sternotomy was avoided in this case. PubMed-ID: 21476890 http://dx.doi.org/10.1089/thy.2010.0405

Metastatic Dormancy and Progression in Thyroid Canc er: Targeting Cells in the Metastatic Frontier. Thyroid, 21(5):487-92. Ringel MD. 2011. BACKGROUND: Metastatic dormancy, or the ability of cancer cells to survive but not progress in metastatic environments, is now recognized to be a common occurrence in cancer. SUMMARY: From a clinical perspective, this phenomenon is common in metastatic well-differentiated thyroid cancer, whereby patients often present with distant metastases that remain stable for years after removal of the primary tumor and subsequent treatment. Experimental data suggest that metastases can develop throughout the life of a cancer and that progression in the distant environment depends on the biology of the cancer cells that metastasize as well as that of the various microenvironments they encounter. A firm understanding of how thyroid cancer cell progression is regulated in different metastatic environments is necessary to devise effective therapies targeting progressive metastatic thyroid cancer. CONCLUSION: In this review, current models of metastatic progression and factors that regulate late-stage metastatic progression that are particularly relevant for thyroid cancer are discussed. PubMed-ID: 21476892 http://dx.doi.org/10.1089/thy.2011.2121

Medullary Thyroid Cancer: Clinico-Pathological Prof ile and Outcome in a Tertiary Care Center in North India. World J Surg, 35(6):1273-80. Mehrotra PK, Mishra A, Mishra SK, Agarwal G, Agarwal A, Verma AK. 2011. BACKGROUND: Recent advances in genetic screening have ushered in a new era in diagnosis and management of medullary thyroid cancer (MTC). However, the same is not true for a resource-poor country, where clinicians are still struggling to diagnose and adequately manage this relatively uncommon thyroid malignancy. We hereby present our experience of managing MTC at a tertiary care referral center in North India. METHODS: This was a retrospective study conducted between January 1990 and July 2009. Demographics, clinical profiles, details of surgical procedures, and follow-up records were reviewed. RESULTS: A total of 71 patients with MTC were identified. Mean age of this group was 39.9+/-14.1 years, and men outnumbered women 1.7:1. Some 84.5% of patients had seemingly sporadic MTC, and 15.5% had familial MTC (MEN2a=14.1%, MEN 2b=1.4%). All patients had a thyroid nodule at the time of presentation. Mean tumor diameter was 4.9 cm. Cervical lymphadenopathy, mediastinal lymphadenopathy, extrathyroidal invasion, and distant metastases were present in 59%, 7.2%, 10%, and 4.2% of patients, respectively. Staging showed that 4.8% of patients were stage I, 17.5% stage II, 14.3% stage III, and 63.6% stage IV. Treatment was as follows: 92.6% of patients had total thyroidectomy (primary or secondary); 67.6% central compartment lymph node dissection, 62.3% lateral cervical lymph node dissection, and 7.2% trans-sternal mediastinal lymph node dissection performed. Some 66.7% of patients suffered from persistent hypercalcitoninemia, and 11.4% of those underwent reoperation. The 5-year and 10-year overall survival (OS) was 74.6% and 58%, respectively. CONCLUSIONS: The majority of the patients with MTC presented at stage IVa, contributing to the high rate of persistent hypercalcitoninemia. Despite a policy of observation and intervening only in overtly symptomatic patients with persistent hypercalcitoninemia, overall survival (OS) in our study was comparable to other series, reinforcing the belief that persistent hypercalcitoninemia has an indolent course in most patients. PubMed-ID: 21479684 http://dx.doi.org/10.1007/s00268-011-1086-7

Thyroid Cancer and Lymph Node Metastases. J Surg Oncol, 103(6):615-8. Clark OH. 2011. There is considerable controversy about the prognostic implications of lymph node metastases in patients with papillary thyroid cancer and whether patients with papillary thyroid cancer should have a prophylactic or selective central (level VI) neck dissection. Some experts report that a prophylactic ipsilateral neck dissection results in fewer patients having elevated thyroglobulin levels but others do not agree. A comprehensive review of the literature suggests that the presence of macroscopic metastases of papillary thyroid cancer in cervical lymph nodes results in a higher recurrence rate and increased death rate, especially in patients 45 years of age or


older, whereas microscopic nodal metastases do not appear to adversely influence survival. Until more information is available we recommend preoperative ultrasonography and a selective ipsilateral neck dissection for patients with papillary thyroid cancer. PubMed-ID: 21480256 http://dx.doi.org/10.1002/jso.21804

Elevated Risk of Papillary Thyroid Cancer in Korean Patients With Hashimoto's Thyroiditis. Head Neck, 33(5):691-5. Kim KW, Park YJ, Kim EH, Park SY, Park dJ, Ahn SH, Park dJ, Jang HC, Cho BY. 2011. BACKGROUND: Hashimoto's thyroiditis (HT) and higher levels of thyroid-stimulating hormone (TSH) have been proposed as risk factors for papillary thyroid cancer (PTC), but this issue is still being debated. The purpose of this study was whether HT was related to the risk of PTC over TSH. METHODS: We enrolled 1329 patients (1028 with PTC, 52 with follicular thyroid cancer, and 249 with benign disease) of 1490 patients who underwent thyroidectomy. RESULTS: The TSH concentration was not different among patients with PTC or benign disease. Our study showed that men (odds ratio [OR] = 1.54; p = .049) and the presence of HT (OR = 2.96; p <.001) increased the risk of PTC. Moreover, HT was associated with multifocal cancer (p = .005) and smaller tumor size (p = .031), but it did not influence the extrathyroidal invasion or nodal metastasis. CONCLUSION: Clinicians who deal with thyroid nodules should pay particular attention to HT because it is a stronger predictor for PTC than other risk factors. PubMed-ID: 21484918 http://dx.doi.org/10.1002/hed.21518

Gasless Endoscopic Thyroidectomy Via an Anterior Ch est Approach--a Review of 219 Cases With Benign Tumor. World J Surg, 35(6):1281-6. Huang XM, Sun W, Zeng L, Liu X, Lu X, Xu YD, Zhang ZG, Xu G. 2011. BACKGROUND: To get a better cosmetic effect, and to avoid even a small incision and scar in the anterior neck zone, we adapted gasless endoscopic thyroidectomy via anterior chest approach. METHODS: From June 2004 to June 2008, 219 patients with thyroid diseases underwent gasless endoscopic thyroidectomy via anterior chest approach. The clinical and pathologic characteristics of patients, the type of operation, operative time, length of postoperative hospital stay, and postoperative complications were analyzed retrospectively. RESULTS: All 219 operations were successfully performed endoscopically. Only three patients showed temporary paralysis of the recurrent laryngeal nerve (RLN), and all of them recovered within 1-3 months after the surgery. One patient showed permanent paralysis of the RLN, one patient developed a postoperative seroma, and one patient suffered a tracheal injury. There were no injuries to the superior laryngeal nerve or any hypoparathyroidism. No further complications, such as irritating cough, tetany, and emphysema developed after the operation. Because of the anterior chest wall approach, none of the patients had a surgical scar on the neck and all were satisfied with the cosmetic effect. CONCLUSIONS: Gasless endoscopic thyroid surgery through anterior chest approach is a feasible and safe method. This technique had better cosmetic results and could constitute a new treatment modality for patients with benign tumors and can also be an effective alternative treatment for the selected patients with thyroid cancer. PubMed-ID: 21487847 http://dx.doi.org/10.1007/s00268-011-1087-6

Prophylactic Central Lymph Node Dissection for Clin ically Node-Negative Papillary Thyroid Microcarcinoma: Influence on Serum Thyroglobulin Le vel, Recurrence Rate, and Postoperative Complications. Surgery, So YK, Seo MY, Son YI. 2011. BACKGROUND: In papillary thyroid microcarcinoma (PTMC), regional lymph node metastasis (LNM) is associated with a increased locoregional recurrence rate. Yet, prophylactic central lymph node dissection (CLND) targeting subclinical central LNM continues to be a matter of debate in the treatment of PTMC, which generally carries an excellent prognosis. The aim of our study was to investigate the benefits and risks of prophylactic CLND in patients with clinically node-negative PTMC. METHODS: This study included 232 patients who underwent surgery for clinically node-negative PTMC from 1999 to 2006. Of these 232 patients, 113 underwent only total thyroidectomy (TT) and 119 underwent TT in conjunction with prophylactic bilateral CLND (TT with CLND). We then compared serum thyroglobulin (Tg) levels, recurrence rates, and postoperative complications between the 2 groups (TT only and TT with CLND). RESULTS: The postoperative stimulated serum Tg level was significantly less in the TT with CLND group than in the TT only group (1.07 vs 2.24 ng/mL,


respectively; P = .022). The stimulated Tg levels in the 2 groups became similar, however, after low-dose radioactive iodine treatment (0.44 ng/mL vs 0.69 ng/mL, respectively; P = 0.341). There was no significant difference in 3-year locoregional control rates after TT with CLND and TT only (98.3% vs 96.5%, respectively; P = .368). Although the frequency of permanent hypocalcemia was approximately 3 times greater in the TT with CLND group (5.6%) than in the TT only group (1.8%), this finding did not reach statistical significance. CONCLUSION: With prophylactic CLND, the postoperative Tg level can significantly decrease. However, prophylactic CLND is not helpful in decreasing short-term locoregional recurrence in patients with clinically node-negative PTMC. Finally, the risk of permanent hypocalcemia may increase after CLND. PubMed-ID: 21497873 http://dx.doi.org/10.1016/j.surg.2011.02.004

Delayed Initial Radioactive Iodine Therapy Resulted in Poor Survival in Patients With Metastatic Differentiated Thyroid Carcinoma: a Retrospective S tatistical Analysis of 198 Cases. J Nucl Med, 52(5):683-9. Higashi T, Nishii R, Yamada S, Nakamoto Y, Ishizu K, Kawase S, Togashi K, Itasaka S, Hiraoka M, Misaki T, Konishi J. 2011. To elucidate the prognostic role of (131)I radioactive iodine therapy (RIT), we conducted a retrospective cohort study analyzing the clinical factors that affect survival of postoperative patients with differentiated thyroid carcinoma (DTC). METHODS: We included 198 DTC patients with extrathyroidal extension who received total or near-total thyroidectomy and then RIT in our hospital from January 1997 to June 2009: patients with lymph node metastases only (n = 47), lung metastases without bone metastases (n = 105), or bone metastases and other distant metastases (lung, liver, brain, and skin) (n = 46). Hemithyroidectomy or subtotal thyroidectomy had been performed before total or near-total thyroidectomy in 59 patients. Disease-specific survival after initial RIT was statistically evaluated using relevant clinical parameters, including age at initial RIT, pathology, sex, therapeutic history before initial RIT, pre- and posttherapeutic serum thyroglobulin ("prethyroglobulin" and "postthyroglobulin," respectively) at initial RIT, thyroglobulin under thyroid-stimulating hormone stimulation at initial RIT ("peak thyroglobulin"), grade of uptake at scintigraphy, extent of metastasis, and number of total RITs. RESULTS: During follow-up after initial RIT (average, 5.37 y), 24 patients died from DTC (11 male patients and 13 female). The most common reasons for death were respiratory failure due to lung metastases (n = 11) and uncontrollable brain metastases (n = 6). Univariate analysis showed that disease-specific survival was related to the following factors: extent of metastasis, age at initial RIT (<45 y), prethyroglobulin (<125 ng/mL), peak thyroglobulin (<1,000 ng/mL), and interval from total thyroidectomy to initial RIT (<180 d). A past history of hemithyroidectomy or subtotal thyroidectomy was not related to disease-specific survival. Multivariate analysis showed 3 factors to be independent prognostic factors--grade of (131)I uptake at whole-body scintigraphy, extent of metastasis, and interval to RIT (P </= 0.001, 0.010, and 0.005, respectively)--and also showed that risk of death in patients with an interval over 180 d was 4.22 times higher than in those with an interval within 180 d. Kaplan-Meier analysis revealed that a shorter interval (180, 365, or 1,000 d) had prognostic value even in the subgroups 45 y or older, with lung metastases, and with bone metastases or more. CONCLUSION: The present study suggests that delaying initial RIT until more than 180 d after total thyroidectomy may result in poor survival for DTC patients. PubMed-ID: 21498534 http://dx.doi.org/10.2967/jnumed.110.081059

Lateral Cervical Lymph Node Metastases From Papilla ry Thyroid Carcinoma: Predictive Factors of Nodal Metastasis. Surgery, 150(1):116-21. Lim YS, Lee JC, Lee YS, Lee BJ, Wang SG, Son SM, Kim IJ. 2011. BACKGROUND: Papillary thyroid carcinoma (PTC) frequently metastasizes to the regional neck; skip metastasis (metastasis to the lateral compartment in the absence of central disease) is uncommon. This prospective study was to evaluate the incidence of occult lateral neck metastasis (LNM) and elucidated the factors that predict LNM in PTC with central neck metastasis (CNM) by performing prophylactic selective lateral neck dissection (SND). METHODS: Sixty-two patients with PTC without clinical LNM underwent total thyroidectomy with central compartment neck dissection and prophylactic SND consecutively after ipsilateral CNM was confirmed by intraoperative frozen biopsy. RESULTS: The incidence of occult LNM in PTC was 55%. Patients with LNM had a larger primary tumor and more positive ipsilateral and bilateral central lymph nodes than patients without LNM. There were no differences between patients with and without LNM with regard to age and extrathyroidal extension. The incidence of occult LNM increased significantly as the number of metastatic ipsilateral and bilateral lymph nodes increased. Independent risk factors for occult LNM were tumor size and the number of positive bilateral lymph nodes (odds ratio [OR] = 1.449; OR = 1.110, respectively). The most common metastatic


site was level III (68%: 23/34), followed by level IV (59%: 20/34) and level II (21%: 7/34). CONCLUSION: The important risk factors for LNM in PTC are primary tumor size and the number of positive bilateral central lymph nodes. Prophylactic SND may be considered in selected patients with a large number of positive central lymph nodes and large tumors. PubMed-ID: 21507446 http://dx.doi.org/10.1016/j.surg.2011.02.003

The Outcomes of First Reoperation for Locoregionall y Recurrent/Persistent Papillary Thyroid Carcinoma in Patients Who Initially Underwent Total Thyroidec tomy and Remnant Ablation. J Clin Endocrinol Metab, 96(7):2049-56. Yim JH, Kim WB, Kim EY, Kim WG, Kim TY, Ryu JS, Gong G, Hong SJ, Shong YK. 2011. CONTEXT: The primary treatment of locoregionally recurrent/persistent papillary thyroid cancer (PTC) is surgical removal by reoperation. However, there had been only limited number of reports on the outcome of reoperation. OBJECTIVE: This study was to evaluate the efficacy of the first reoperation for locoregionally recurrent/persistent papillary thyroid carcinoma and the usefulness of stimulated thyroglobulin for evaluating efficacy of reoperation. Design and SETTINGS: This was a retrospective observational cohort study in a tertiary referral hospital. PATIENTS: A total of 83 patients, who underwent initial total thyroidectomy and nodal dissection with radioactive iodine remnant ablation, received reoperation for locoregionally recurrent/persistent PTC and were included in this study. Stimulated thyroglobulin levels were assessed before and after reoperation. MAIN OUTCOME MEASURES: We assessed biochemical remission (stimulated thyroglobulin <1 ng/ml) after reoperation and evaluated second clinical recurrence-free survival rate according to stimulated thyroglobulin value. RESULTS: There was a significant positive correlation between the numbers of resected malignant lymph nodes and the reduction in stimulated thyroglobulin level after reoperation. Biochemical remission was achieved in 51% of patients who underwent first reoperation. Patients with stimulated thyroglobulin level greater than 5 ng/ml after first reoperation had a greater chance of a second clinical recurrence (the estimated 5 yr clinical recurrence free survival rate, 94 +/- 3 vs.74 +/- 9%, log rank statistics 15.8, df = 1, P < 0.001). CONCLUSION: Surgery is an effective option for managing locally recurrent/persistent PTC. Stimulated thyroglobulin is a useful marker for evaluating efficacy of reoperation and predicting second recurrence in locoregionally recurrent/persistent PTC. PubMed-ID: 21508143 http://dx.doi.org/10.1210/jc.2010-2298

Robot-Assisted Endoscopic Thyroidectomy: Has the Ti me Come to Abandon Neck Incisions? Ann Surg, 253(6):1067-8. Duh QY. 2011. PubMed-ID: 21522010 http://dx.doi.org/10.1097/SLA.0b013e31821c4e48

Central Compartment Neck Dissection for Thyroid Can cer: a Surgical Technique. World J Surg, 35(7):1553-9. Hartl DM, Travagli JP. 2011. Several professional societies have in the past few years joined forces to standardize and define terminology for central compartment neck dissection, with the objective of improving communication among professionals and encouraging a more uniform surgical approach to neck nodes. Precisely defining and describing a technique has the advantage of providing a basis for communication and for discussion. A basic technique should be reproducible with low morbidity and teachable to surgeons in training. We herein describe a basic technique for bilateral central compartment neck dissection for thyroid cancer. PubMed-ID: 21533648 http://dx.doi.org/10.1007/s00268-011-1105-8

Patterns of Lymph Node Metastases in Papillary Thyr oid Carcinoma: Results From Consecutive Bilateral Cervical Lymph Node Dissection. World J Surg, 35(7):1560-6. Takada H, Kikumori T, Imai T, Sawaki M, Shibata A, Kiuchi T. 2011. BACKGROUND: In patients with papillary thyroid carcinoma (PTC), the appropriate extent of lymph node dissection has not yet been established due to lack of accurate patterns of lymph node metastases (LNM). The aim of this study was to clarify the LNM pattern in PTC patients based on our institution's experience with a consistent technique of bilateral neck dissection, and to consider the rational extent of lymph node dissection. METHODS: Between 1990 and 1999, 152 consecutive patients with PTC who underwent curative total


thyroidectomy and bilateral neck dissection as initial treatment were analyzed. The patterns of LNM according to clinicopathological classification were analyzed using the lymph node ratio (LNR; number of metastatic lymph nodes/number of dissected nodes) and frequency (FLNM; number of patients with LNM/number of dissected patients) in cervical compartments. RESULTS: Regardless of clinicopathological classification, LNR in the central compartment was consistently higher than in other compartments, and FLNM in the ipsilateral lateral compartment was consistently higher than in other compartments except for multifocal tumors. The LNR and FLNM in the contralateral lateral compartment were significantly higher in advanced (>/=T3) cases than in cases with smaller tumors (T1) and were comparable to those in the ipsilateral lateral compartment in advanced (>/=T3) cases. CONCLUSIONS: The pattern of LNR provided a better reflection of the patterns of LNM. In terms of the LNR, central neck dissection is the basic extent of lymph node dissection for all clinically apparent PTC. In advanced patients, it is also advisable to include bilateral lateral neck dissection. PubMed-ID: 21538186 http://dx.doi.org/10.1007/s00268-011-1133-4

Approach to the Patient With Nontoxic Multinodular Goiter. J Clin Endocrinol Metab, 96(5):1202-12. Bahn RS, Castro MR. 2011. Thyroid nodules are very common, and although the majority are benign, approximately 5% may harbor malignancy. The evaluation of the patient with solitary thyroid nodule is generally straightforward and will typically include measurement of serum TSH to assess thyroid function and fine-needle aspiration biopsy of the nodule, with or without ultrasound (US) guidance. The approach to the patient with nontoxic multinodular goiter represents a more difficult problem for the clinician. All patients should have serum TSH measured to assess functional thyroid status and US examination to evaluate the number, size, and sonographic features of the nodules and assist in the selection of nodules that may need fine-needle aspiration biopsy. Patients with nodules yielding malignant cytology should be referred for surgery. Given the lack of reliable markers to predict biological behavior of nodules with suspicious (indeterminate) cytology, patients with such nodules are generally advised to have surgery, unless autonomous function of these nodules can be confirmed by scintigraphy. Most of these patients, however, will ultimately prove to have benign follicular tumors. Many patients with benign but large goiters may experience clinical symptoms of pressure, such as dysphagia, choking sensation, or airway obstruction. Such patients will often require surgery for alleviation of symptoms. In the absence of malignancy, asymptomatic patients may be observed. Radioactive iodine, commonly used in many parts of Europe, is safe and effective and may be a reasonable option for many patients. Periodic follow-up with neck palpation and US exam is recommended for all patients. PubMed-ID: 21543434 http://dx.doi.org/10.1210/jc.2010-2583

Outpatient Thyroidectomy: Is It a Safe and Reasonab le Option? Am J Surg, 201(5):565-8. Hessman C, Fields J, Schuman E. 2011. BACKGROUND: Outpatient surgery is cost effective and convenient. The aim of this study was to determine the safety and feasibility of outpatient thyroidectomy. METHODS: Retrospective review was performed of all thyroidectomy patients from a tertiary care center between January 2004 and March 2010. RESULTS: One hundred forty-eight patients met the inclusion criteria. Subtotal and hemithyroidectomies (n = 79) were compared against completion and total thyroidectomies (n = 72). Nine total thyroidectomy patients (12.5%) required unplanned overnight admission, compared with 4 hemithyroidectomy patients (5.1%) (P = .15). The majority were admitted for pain and nausea control. Overnight admissions were highest among men (32% vs 5%, P = .002) and patients with Graves' disease (36% vs 6%, P = .003). Postoperative complications occurred in 6 total thyroidectomy patients (8.3%) and 3 hemithyroidectomy patients (3.8%) (P = .31). Only 4 patients (2.6%) required readmission for complications. There were no deaths. CONCLUSIONS: Outpatient thyroidectomy performed by an experienced surgeon is safe and feasible. Men and patients with Graves' disease have a higher probability of requiring postoperative admission. PubMed-ID: 21545900 http://dx.doi.org/10.1016/j.amjsurg.2011.01.023

Utilization of Thyroidectomy for Benign Disease in the United States: a 15-Year Population-Based Study . Am J Surg, 201(5):570-4. Ho TW, Shaheen AA, Dixon E, Harvey A. 2011. BACKGROUND: Recent recommendations suggest that total thyroidectomy (TT) is the preferred treatment for benign thyroid disease. This approach remains controversial because of the increased risk of morbidity


compared with a partial thyroidectomy (PT). The aim of this study was to determine the use of thyroidectomy for benign disease over a 15-year period. METHODS: One hundred nineteen thousand eight hundred eighty-five patients from the Nationwide Inpatient Sample database (1993-2007) underwent surgery for benign thyroid disease. Logistic regression was used to assess the relation between extent of thyroidectomy and the year of admission, hospital volume, and surgical outcomes. RESULTS: The use of TT increased from 17.6% (1993-1997) to 39.6% (2003-2007) compared with 82.4% and 60.4% for PT over the same periods (P < .0001). A greater proportion of TTs was performed in high-volume centers in which the rates of postoperative complications were lower than low-volume centers. CONCLUSIONS: The use of TT for benign thyroid disease has increased over the last 15 years in the United States. This pattern of practice is in keeping with the trends reported in recent literature. PubMed-ID: 21545901 http://dx.doi.org/10.1016/j.amjsurg.2010.12.006

Immunophenotyping of Thyroid Tumors Identifies Mole cular Markers Altered During Transformation of Differentiated into Anaplastic Carcinoma. Am J Surg, 201(5):580-6. Wiseman SM, Griffith OL, Gown A, Walker B, Jones SJ. 2011. BACKGROUND: The objective of this study was to evaluate the change in the tumor expression profile that occurs during the transformation of differentiated thyroid cancer (DTC) into anaplastic thyroid cancer (ATC) and to evaluate an 8-marker transformation panel previously identified through evaluation of ATCs and their adjacent associated DTCs. METHODS: Tissue microarrays were constructed from 19 ATCs and 96 DTCs (90 papillary carcinomas and 6 follicular carcinomas), and immunohistochemistry was used to evaluate the expression of 54 molecular markers. Significant associations between marker staining and cancer pathology (DTC vs ATC) were determined using contingency table and marginal homogeneity tests. A Random Forests classifier algorithm was also used to identify useful or important molecular classifiers. RESULTS: Overall, there were 25 significantly differentially expressed markers when comparing ATCs with DTCs. These included 5 of the 8 markers that were previously identified as being altered during anaplastic transformation and 3 additional markers were also found to be highly significantly differentially expressed by ATCs and DTCs. Clustering and classification analysis based on the previously identified 8-marker transformation panel, or the 5 of these markers that were found to be most important in the current study, readily separated DTC and ATC with a high degree of accuracy. CONCLUSIONS: The markers observed to change during thyroid cancer progression validate prior observations and represent promising molecular diagnostic or prognostic tools and identify targets for therapy of ATC. PubMed-ID: 21545903 http://dx.doi.org/10.1016/j.amjsurg.2011.01.010

Determinants of Postoperative Hypocalcemia in Vitam in D-Deficient Graves' Patients After Total Thyroidectomy. Am J Surg, 201(5):685-91. Erbil Y, Ozbey NC, Sari S, Unalp HR, Agcaoglu O, Ersoz F, Issever H, Ozarmagan S. 2011. BACKGROUND: The etiology of postoperative hypocalcemia after total thyroidectomy appears to be multifactorial, that is, postoperative transient hypoparathyroidism, low 25-hydroxy vitamin D (25-OHD) concentrations, aging, and hyperthyroidism with increased bone turnover. Our aim was to evaluate the factors responsible for postoperative hypocalcemia in euthyroid vitamin D-deficient/insufficient Graves patients who underwent total thyroidectomy at our institution. METHODS: Thirty-five consecutive patients with Graves disease treated by total thyroidectomy were included in the present study. All patients were vitamin D deficient/insufficient (ie, 25-OHD concentrations of <20/<30 ng/mL, respectively). Patients were divided into 2 groups according to postoperative serum albumin corrected calcium concentrations: group 1 (n = 13) patients had postoperative serum calcium concentrations of 8 mg/dL or less; group 2 (n = 22) patients had serum calcium concentrations greater than 8 mg/dL. Bone turnover markers (deoxypiridinoline, bone-specific alkaline phosphatase) and 25-OHD were determined the day before surgery. RESULTS: In group 1 patients, disease duration was significantly longer, 25-OHD and postoperative parathyroid hormone concentrations were significantly lower, and bone turnover markers were significantly higher. Logistic regression analysis revealed that a postoperative parathyroid hormone concentration less than 10 pg/mL was the most powerful parameter to predict postoperative hypocalcemia (odds ratio, 23; 95% confidence interval, 3.3-156). CONCLUSIONS: In Graves patients with vitamin D deficiency/insufficiency, postoperative (transient) hypoparathyroidism is the most significant parameter to determine the development of postoperative hypocalcemia. PubMed-ID: 21545922 http://dx.doi.org/10.1016/j.amjsurg.2010.04.030


First Reported Case of Unilateral Graves' Disease i n the Left Lobe of a Bilobar Thyroid Gland. Thyroid, 21(6):683-6. Chen LC, Green JB. 2011. BACKGROUND: Unilateral Graves' disease is a rare disease variant that can occur in a bilobar thyroid gland. We report the first documented case of unilateral Graves' disease in the left lobe of a bilobar thyroid gland and review the pertinent literature. PATIENT FINDINGS: A 48-year-old man presented in June 2010 with thyrotoxicosis. I-131 radioisotope uptake was elevated at 33.4%, and scintigraphy revealed that uptake of the radioisotope was uniformly increased in the left lobe of the thyroid gland. Ultrasonography of the thyroid gland revealed a non-nodular, enlarged, and heterogeneous left lobe; Doppler investigation of the lobe showed hypervascularity classically seen in Graves' disease. The right lobe of the thyroid, on the other hand, appeared homogeneous and hypovascular on ultrasonography. Thyroid-stimulating immunoglobulin was significantly elevated at 191% (reference range <140%). Unilateral Graves' disease was the most likely diagnosis. SUMMARY: As has occasionally been described in the literature, unilateral involvement of the thyroid gland is a rare presentation of Graves' disease. Pre-existing functional or structural differences (either congenital or acquired) between the two lobes may contribute to this rare presentation. To our knowledge, this is the first reported case of unilateral Graves' disease presenting in the left lobe of a bilobar thyroid gland. CONCLUSION: Although the pathophysiology of unilateral Graves's disease has not been clearly elucidated, clinicians should be aware that Graves' disease can present unilaterally in either lobe of the thyroid gland. PubMed-ID: 21563918 http://dx.doi.org/10.1089/thy.2010.0343

Five-Year Survival Is Similar in Thyroid Cancer Pat ients With Distant Metastases Prepared for Radioactive Iodine Therapy With Either Thyroid Horm one Withdrawal or Recombinant Human TSH. J Clin Endocrinol Metab, 96(7):2105-11. Tala H, Robbins R, Fagin JA, Larson SM, Tuttle RM. 2011. CONTEXT: Elevated levels of TSH markedly enhance the effectiveness of radioiodine (RAI) therapy in metastatic thyroid cancer. OBJECTIVE: The objective of the study was to compare short-term overall survival in thyroid cancer patients with RAI-avid distant metastases prepared for RAI therapy with either traditional thyroid hormone withdrawal (THW) or recombinant human TSH (rhTSH) stimulation. DESIGN: This was a retrospective chart review. SETTING: The study was conducted at a tertiary care comprehensive cancer center. PATIENTS: Patients included 175 patients with RAI avid metastatic disease to lung and/or bone. INTERVENTIONS: In 58 patients, all RAI treatments (remnant ablation and therapy of metastatic disease) were done with rhTSH stimulation. In 35 patients, all RAI treatments were done after THW. In 82 patients, THW was used for initial RAI treatment(s) with subsequent administered activities given after rhTSH stimulation. MAIN OUTCOME MEASURE: Overall survival was measured. RESULTS: After a median follow-up of 5.5 yr, there were no significant differences in overall survival between patients prepared for RAI therapy with rhTSH alone, THW alone, or THW followed by rhTSH (Kaplan-Meier analysis, P = 0.80). In a multivariate analysis that included clinicopathological features and method of preparation (rhTSH or TWH), only age at diagnosis was an independent predictor of overall survival. CONCLUSIONS: Preparation for RAI therapy using either THW or rhTSH stimulation was associated with similar 5-yr overall survival rates in patients with RAI avid thyroid cancer metastases to lung or bone. PubMed-ID: 21565788 http://dx.doi.org/10.1210/jc.2011-0305

Excellence in Robotic Thyroid Surgery: a Comparativ e Study of Robot-Assisted Versus Conventional Endoscopic Thyroidectomy in Papillary Thyroid Micro carcinoma Patients. Ann Surg, 253(6):1060-6. Lee S, Ryu HR, Park JH, Kim KH, Kang SW, Jeong JJ, Nam KH, Chung WY, Park CS. 2011. OBJECTIVE: To confirm the merits of robotic thyroid surgery by comparing the surgical outcomes of robotic-assisted and conventional endoscopic thyroidectomy in papillary thyroid microcarcinoma (PTMC) patients. BACKGROUND: Robot-assisted surgical techniques are widely utilized, and substantially, overcome the limitations of conventional endoscopic surgery. Furthermore, recently, robotic procedures were introduced to the thyroidectomy field. METHODS: From November 2001 to July 2009, 1150 patients with PTMC underwent endoscopic thyroidectomy using a gasless, trans-axillary approach. Of these patients, 580 underwent a robotic procedure (the robotic group; RG) and 570 a conventional endoscopic procedure (the conventional endoscopic group; EG). These 2 groups were retrospectively compared in terms of their clinicopathologic characteristics, early surgical outcomes, and surgical completeness. RESULTS: Total thyroidectomy was performed more frequently in the RG. Although mean operation times were not statistically different, the mean number of central nodes retrieved was greater in the RG than in the EG. Mean tumor size were not significantly different in the 2


groups, but the RG showed more frequent central node metastasis and capsular invasion. Tumor and nodal statuses in the RG were more advanced than in the EG. Regarding postoperative complications, transient hypocalcemia was more frequent in the RG, but other complication frequencies were not significantly different in the 2 groups. Postoperative serum thyroglobulin levels were similar in 2 groups, and short-term follow-up (1 year) revealed no recurrence by sonography and no abnormal uptake during radioactive iodine therapy in either group. CONCLUSIONS: The application of robotic technology to endoscopic thyroidectomy could overcome the limitations of conventional endoscopic surgery during the surgical management of PTMC. PubMed-ID: 21587112 http://dx.doi.org/10.1097/SLA.0b013e3182138b54

Current State and Future Perspective of Molecular D iagnosis of Fine-Needle Aspiration Biopsy of Thyroid Nodules. J Clin Endocrinol Metab, 96(7):2016-26. Ferraz C, Eszlinger M, Paschke R. 2011. CONTEXT: Fine-needle aspiration biopsy (FNAB) is the most sensitive and specific tool for the differential diagnosis of thyroid malignancy. Some limitations of FNAB can be overcome by the molecular analysis of FNAB. This review analyzes the current state and problems of the molecular analysis of FNAB as well as possible goals for increasing the diagnostic rate, especially in the indeterminate/follicular lesion cytological group. EVIDENCE ACQUISITION: Twenty publications were evaluated for the diagnostic material and assay systems used, the type, and the number of mutations screened. Sensitivity, specificity, and false-negative and false-positive rates were calculated for all publications. EVIDENCE SYNTHESIS: Testing for a panel of somatic mutations is most promising to reduce the number of indeterminate FNAB. A mean sensitivity of 63.7% was achieved for indeterminate lesions. However, there is a broad sensitivity range for the investigation of mutations in the indeterminate lesions. Therefore, additional molecular markers should be defined by mRNA and microRNA expression studies and evaluated in FNAB samples of thyroid carcinomas without known somatic mutations, and especially for the many benign nodules in the indeterminate/follicular lesion fine-needle aspiration cytology category. This approach should improve the differential diagnosis of indeterminate/follicular lesion FNAB samples. CONCLUSION: Testing for a panel of somatic mutations has led to an improvement of sensitivity/specificity for indeterminate/follicular proliferation FNAB samples. Further methodological improvements, standardizations, and further molecular markers should soon lead to a broader application of molecular FNAB cytology for the differential diagnosis of thyroid nodules and to a substantial reduction of diagnostic surgeries. PubMed-ID: 21593119 http://dx.doi.org/10.1210/jc.2010-2567

Minimally Invasive Thyroidectomy: a Comprehensive A ppraisal of Existing Techniques. Surgery, 150(1):17-24. Linos D. 2011. PubMed-ID: 21596415 http://dx.doi.org/10.1016/j.surg.2011.02.018

Outcome of Radical Resection and Postoperative Radi otherapy for Thyroid Carcinoma Showing Thymus-Like Differentiation. World J Surg, 35(8):1840-6. Sun T, Wang Z, Wang J, Wu Y, Li D, Ying H. 2011. BACKGROUND: Carcinoma showing thymus-like differentiation (CASTLE) is a rare disease that is difficult to diagnose. The aim of this study was to assess the effects of combined-modality treatment in CASTLE patients. METHODS: We retrospectively studied patients identified between January 1, 2000 and December 31, 2009 as having CASTLE and who subsequently underwent surgery and radiotherapy or chemotherapy. Preoperative laboratory findings, ultrasonographic (US) and computed tomographic (CT) features, and fine-needle aspiration biopsy (FNAB) specimens were evaluated. RESULTS: Seven patients with CASTLE were identified (four men, three women). The median age at initial diagnosis was 48 years (range 25-56 years). The five newly diagnosed patients were treated with curative surgery and postoperative radiotherapy, whereas two patients with recurrent disease were treated with salvage surgery plus radiotherapy or chemotherapy. All patients were disease-free at a median follow-up period of 34 months (range 12-61 months). The pattern of immunohistochemical staining was similar to that of thymic carcinoma. Specimens from all seven patients stained positively for CD5, CD117, and cytokeratin but were uniformly negative for thyroglobulin, thyroid transcription factor 1 (TTF-1), and calcitonin. CONCLUSIONS: Patients with CASTLE have excellent outcomes after curative resection and postoperative radiotherapy compared with patients with anaplastic thyroid carcinoma. Even patients with local recurrent


disease benefited from salvage surgery with subsequent operation and/or radiotherapy. CD5 immunohistochemical staining on FNAB samples may help identify the possible entities that are part of the differential diagnosis. PubMed-ID: 21597887 http://dx.doi.org/10.1007/s00268-011-1151-2

Fine Needle Aspiration of the Thyroid: Correlation With Final Histopathology in a Surgical Series of 7 97 Patients. J Am Coll Surg, 213(1):188-94. Lew JI, Snyder RA, Sanchez YM, Solorzano CC. 2011. BACKGROUND: Fine needle aspiration (FNA) is accepted as the diagnostic procedure of choice in the management of patients with thyroid nodules. Follicular/Hurthle cell neoplasms have traditionally been grouped under the category of indeterminate FNA results. This study examined the experience with FNA in a large cohort of patients undergoing thyroidectomy before adoption of the Bethesda system for reporting thyroid cytopathology (BSTC) at a single academic medical center. STUDY DESIGN: A retrospective review of prospectively collected data of 797 consecutive patients with dominant nodules >1 cm who underwent FNA and thyroidectomy from 2003 to 2009 was performed. Patients were categorized into groups based on FNA results: malignant, benign, indeterminate, and nondiagnostic. The indeterminate group had FNA results that included follicular neoplasm, Hurthle cell neoplasm, and suspicion of papillary thyroid cancer. FNA results were compared with final histopathology after thyroidectomy. RESULTS: FNA results included 147 (18%) positive for malignancy, 255 (32%) benign, 358 (45%) indeterminate, and 37 (5%) nondiagnostic. The overall malignancy rate on final histopathology was 369 of 797 (46%). Overall, there was a false positive rate of 2% and false negative rate of 8.6%. Among the 358 indeterminate FNA results, carcinoma was found in 81 (36%) of 223 follicular neoplasms, 18 (36%) of 50 Hurthle cell neoplasms, and 78 (92%) of 85 that were suspicious for papillary thyroid cancer. When FNA was nondiagnostic, cancer was present in 9 of 37 (24%). Among 39 patients with benign FNA who had cancer on final histopathology, 22 of 255 (8.6%) had cancer in the index thyroid nodule, and 81% of cancers were >1 cm. CONCLUSIONS: Patients with FNA and dominant nodules >1 cm, who underwent thyroidectomy, had an overall rate of thyroid malignancy of 46%. There was a cancer prevalence of 8.6% in patients with benign FNA results referred for surgical resection. Despite not yet implementing the BSTC at this medical center, the majority of thyroidectomies were adequately performed for indeterminate FNAs with underlying malignancy. PubMed-ID: 21601489 http://dx.doi.org/10.1016/j.jamcollsurg.2011.04.029

Thyroid-Associated Paragangliomas. Thyroid, 21(7):725-33. Phitayakorn R, Faquin W, Wei N, Barbesino G, Stephen AE. 2011. BACKGROUND: Paragangliomas in the region of the thyroid gland are rare tumors that can present a diagnostic challenge by mimicking follicular and c-cell derived thyroid tumors. SUMMARY: Thyroid-associated paragangliomas are likely a subset of laryngeal paragangliomas and, although quite rare, should be considered in the differential diagnosis of a hypervascular thyroid nodule. The preoperative diagnosis of thyroid-associated paragangliomas can be challenging since the cytologic and histologic features overlap with more common primary thyroid neoplasms, in particular medullary carcinoma. Differential expression of a panel of immunohistochemical markers, including neuro-specific enolase, chromogranin A, synaptophysin, keratin, and S100, can be used to distinguish thyroid-associated paragangliomas from primary thyroid tumors. Intraoperatively, thyroid-associated paragangliomas may be associated with significant intraoperative bleeding and are often densely adherent to surrounding tissues, including the recurrent laryngeal nerve. Interestingly, the aggressive local behavior of these tumors does not correspond to potential for malignancy, as there are no patients with malignant thyroid-associated paragangliomas reported in the medical literature. Therefore, these tumors may be treated with limited resection. Postoperatively, patients with paragangliomas should receive hormonal evaluation for functional disease, imaging evaluation for multicentric and metastatic disease, and genetic counseling. CONCLUSION: Thyroid-associated paragangliomas are an important part of the differential diagnosis of a hypervascular thyroid nodule, especially in a patient with a fine-needle aspiration biopsy suggestive of medullary thyroid carcinoma, but with unremarkable serum calcitonin levels. Consideration of a thyroid-associated paraganglioma also has important operative and postoperative implications for determining the extent of thyroid resection as well as follow-up testing. PubMed-ID: 21615305 http://dx.doi.org/10.1089/thy.2010.0362


Effects of Physical Activity on Body Composition an d Fatigue Perception in Patients on Thyrotropin-Suppressive Therapy for Differentiated Thyroid Carc inoma. Thyroid, 21(7):695-700. Vigario PS, Chachamovitz DS, Cordeiro MF, Teixeira PF, de Castro CL, de Oliveira FP, Vaisman M. 2011. BACKGROUND: Subclinical thyrotoxicosis (scTox) may be associated with alterations in body composition and fatigue that can be possibly reversed with physical activity. The aim of the present study was to evaluate whether the systematic practice of physical activity improves lower extremity muscle mass and fatigue perception in patients with scTox. MATERIALS AND METHODS: We studied 36 patients (2 men) with median age of 48.0 (43.0-51.0) years, body mass index of 27.4 (22.1-30.2) kg/m(2), thyrotropin <0.4 mU/L, and free thyroxine between 0.8 and 1.9 ng/dL and 48 control subjects (C group; 7 men). Patients were randomly divided in two groups according to the adherence to the exercise training: scTox-Tr (n = 19)-patients who adhered to the exercise intervention and scTox-Sed (n = 17)--patients who did not adhere to it. The C group did not participate in the randomization. The exercise training was supervised by a physical education instructor, and it was composed of 60 minutes of aerobic activity and stretching exercises, twice a week, during 12 weeks. In both groups, body composition was assessed (anthropometric method), and the Chalder Fatigue Scale was determined at baseline and after 3 months of intervention (scTox-Tr group) or observation (scTox-Sed group). RESULTS: At baseline, patients with scTox had lower muscle mass and mid-thigh girth and more fatigue on the Chalder Fatigue Scale than euthyroid control subjects. The scTox-Tr group had an increase in muscle mass, reduction in the variables reflecting whole body fat, and lesser perception of fatigue during the exercise training period (p </= 0.05 for these parameters at the start and end of the exercise training period). CONCLUSIONS: scTox is associated with lower muscle mass and mid-thigh girth and more fatigue. Physical activity training can partially ameliorate these characteristics. More studies are needed to determine what training program would be optimum, both in terms of beneficial effects and for avoiding potential adverse responses. PubMed-ID: 21615309 http://dx.doi.org/10.1089/thy.2010.0052

Prognosis and Prognostic Factors for Distant Metast ases and Tumor Mortality in Follicular Thyroid Carcinoma. Thyroid, 21(7):751-7. Sugino K, Ito K, Nagahama M, Kitagawa W, Shibuya H, Ohkuwa K, Yano Y, Uruno T, Akaishi J, Kameyama K, Ito K. 2011. BACKGROUND: Distant metastases are more common in patients with follicular thyroid carcinoma (FTC) than in patients with papillary thyroid carcinoma, and the outcome is often poorer in patients with distant metastases. In this study, we attempted to identify the risk factors for distant metastases in FTC. METHODS: Between 1989 and 1997, 134 patients with FTC underwent initial surgery, and their median follow-up period was 12.5 years. Seventeen patients had widely invasive FTC, and 117 had minimally invasive FTC. Distant metastases were observed in 36 patients (26.9%). Thirteen of these patients had distant metastases at the time of initial surgery (M1), and in the other 23 patients distant metastases were diagnosed with during their follow-up periods. Risk factors for distant metastases and cause-specific survival were analyzed. The factors analyzed were age at the time of initial surgery, sex, primary tumor size, histological findings (invasiveness, extent of vascular, and capsular invasion), and distant metastases at the time of initial surgery. RESULTS: Univariate analysis showed that age and primary tumor size were significant factors related to postoperative distant metastases in the group of 121 patients who did not have distant metastases at the time of initial surgery. When the patients with M1 were included, the cumulative distant metastases-free-survival rate was significantly lower in the group with widely invasive FTC. The cumulative survival rate was significantly higher in the groups of patients with the minimally invasive type, who were under 45 years old, whose primary tumor size was under 4 cm and who did not have distant metastases at the time of the initial surgery. Multivariate analyses showed that tumor size and age were significant risk factors for postoperative distant metastases and that age and the presence of distant metastases at the time of the initial surgery were significant risk factors for poorer cause-specific survival. CONCLUSION: Age and primary tumor size were significant risk factors for postoperative distant metastases. Based on the findings in this study, we conclude that conservative management is sufficient for younger patients with minimally invasive FTC whose primary tumor is small. PubMed-ID: 21615311 http://dx.doi.org/10.1089/thy.2010.0353

The Need for Standardized Technique in Intraoperati ve Monitoring of the External Branch of the Superio r Laryngeal Nerve During Thyroidectomy. Surgery, 149(6):854-5. Mangano A, Dionigi G. 2011.


PubMed-ID: 21621687 http://dx.doi.org/10.1016/j.surg.2011.03.004

Iodine Status of UK Schoolgirls: a Cross-Sectional Survey. Lancet, 377(9782):2007-12. Vanderpump MP, Lazarus JH, Smyth PP, Laurberg P, Holder RL, Boelaert K, Franklyn JA. 2011. BACKGROUND: Iodine deficiency is the most common cause of preventable mental impairment worldwide. It is defined by WHO as mild if the population median urinary iodine excretion is 50-99 mug/L, moderate if 20-49 mug/L, and severe if less than 20 mug/L. No contemporary data are available for the UK, which has no programme of food or salt iodination. We aimed to assess the current iodine status of the UK population. METHODS: In this cross-sectional survey, we systematically assessed iodine status in schoolgirls aged 14-15 years attending secondary school in nine UK centres. Urinary iodine concentrations and tap water iodine concentrations were measured in June-July, 2009, and November-December, 2009. Ethnic origin, postcode, and a validated diet questionnaire assessing sources of iodine were recorded. FINDINGS: 810 participants provided 737 urine samples. Data for dietary habits and iodine status were available for 664 participants. Median urinary iodine excretion was 80.1 mug/L (IQR 56.9-109.0). Urinary iodine measurements indicative of mild iodine deficiency were present in 51% (n=379) of participants, moderate deficiency in 16% (n=120), and severe deficiency in 1% (n=8). Prevalence of iodine deficiency was highest in Belfast (85%, n=135). Tap water iodine concentrations were low or undetectable and were not positively associated with urinary iodine concentrations. Multivariable general linear model analysis confirmed independent associations between low urinary iodine excretion and sampling in summer (p<0.0001), UK geographical location (p<0.0001), low intake of milk (p=0.03), and high intake of eggs (p=0.02). INTERPRETATION: Our findings suggest that the UK is iodine deficient. Since developing fetuses are the most susceptible to adverse effects of iodine deficiency and even mild perturbations of maternal and fetal thyroid function have an effect on neurodevelopment, these findings are of potential major public health importance. This study has drawn attention to an urgent need for a comprehensive investigation of UK iodine status and implementation of evidence-based recommendations for iodine supplementation. FUNDING: Clinical Endocrinology Trust. PubMed-ID: 21640375 http://dx.doi.org/10.1016/S0140-6736(11)60693-4

Prognostic Impact of Serum Thyroglobulin Doubling-T ime Under Thyrotropin Suppression in Patients With Papillary Thyroid Carcinoma Who Underwent Tota l Thyroidectomy. Thyroid, 21(7):707-16. Miyauchi A, Kudo T, Miya A, Kobayashi K, Ito Y, Takamura Y, Higashiyama T, Fukushima M, Kihara M, Inoue H, Tomoda C, Yabuta T, Masuoka H. 2011. BACKGROUND: Detectable serum thyroglobulin (Tg) in patients with papillary thyroid carcinoma (PTC) after total thyroidectomy implies unsuccessful surgery, indicating a high risk of recurrence. Serum Tg kinetics in such patients have not been extensively studied. We studied serum Tg kinetics in patients with suppressed serum thyrotropin levels and undetectable anti-Tg antibody to minimize the effects of these factors on Tg values, and evaluated the relationship of prognosis to the serum Tg doubling-time. METHODS: Between January 1998 and December 2004, 1515 patients with PTC underwent total thyroidectomy in Kuma Hospital. After excluding patients with other thyroid cancers and those positive tests for anti-Tg antibody, there were 426 patients with 4 or more serum Tg measurements at a time that serum thyrotropin concentrations were <0.1 mIU/L. These patients were selected for the present retrospective study. Tg doubling-time was computed using Tg values measured during routine follow-up. Patients were followed for a mean of 88.1 months and a median of 86.7 months. RESULTS: Of the 426 patients, 137 patients had 4 or more measurements that revealed detectable Tg in serum Tg. The Tg doubling-time (DT), calculated using all available data, varied widely, and were grouped into those that were <1 year (17 patients), those that were 1-3 years (21 patients), and those that were >/= 3 years (30 patients), as well as those with a negative value due to decrease in serum Tg (69 patients). There were also 88 patients who had three or fewer serum Tg measurements that showed detectable Tg levels, as well as 201 patients in whom serum Tg measurements were below the lower limit of detection. In the group of patients with a Tg-DT of <1 year the cause specific survival at 10 years was 50%, and in the group with a Tg-DT of 1-3 years it was 95%. In all other groups it was 100%. Many classical prognostic factors (TNM stage, age, and gender) as well as the Tg-DT were significant indicators of survival by univariate analysis, but Tg-DT remained the only independent predictor by multivariate analysis. Tg-DT was also the only independent predictor of distant metastases and loco-regional recurrence on multivariate analysis. Tg-DT calculated using only the first four data [Tg-DT (first four data)] was also the only independent predictor of survival, distant metastases, and loco-regional recurrence on multivariate analysis. CONCLUSIONS: Tg-DT (all data or first four data) is a very strong prognostic predictor superior to the classical prognostic factors in patients with PTC.


PubMed-ID: 21649472 http://dx.doi.org/10.1089/thy.2010.0355

Initial Experience With a Gasless Unilateral Axillo -Breast or Axillary Approach Endoscopic Thyroidectomy for Papillary Thyroid Microcarcinoma: Comparison With Conventional Open Thyroidectomy. Surg Laparosc Endosc Percutan Tech, 21(3):162-9. Tae K, Ji YB, Cho SH, Kim KR, Kim DW, Kim DS. 2011. The efficacy of various endoscopic thyroidectomy has not been determined for papillary thyroid microcarcinoma (PTMC). We compared 31 consecutive patients with PTMC who underwent endoscopic thyroidectomy by a gasless unilateral axillo-breast or axillary approach, and the 36 PTMC patients who underwent conventional open thyroid lobectomy from August 2005 to December 2008. There were more female patients (P=0.004) in the endoscopic group, and the mean age of endoscopic group was younger than that of the open thyroidectomy group (P=0.006). The entire endoscopic thyroidectomy was successfully completed in all the patients. The operative time was longer for those undergoing endoscopic thyroidectomy (P<0.001). The complication rate did not differ between the 2 groups. The cosmetic satisfaction, as evaluated by questionnaire, was greater in the endoscopic group (P<0.001). Endoscopic thyroidectomy by a gasless unilateral axillo-breast or axillary approach for selected cases of PTMC is a feasible, safe, and cosmetically superior procedure. PubMed-ID: 21654299 http://dx.doi.org/10.1097/SLE.0b013e318218d1a4

New American Thyroid Association and American Assoc iation of Clinical Endocrinologists Guidelines for Thyrotoxicosis and Other Forms of Hyperthyroidi sm: Significant Progress for the Clinician and a Guide to Future Research. Thyroid, 21(6):573-6. Pearce EN, Hennessey JV, McDermott MT. 2011. PubMed-ID: 21663417 http://dx.doi.org/10.1089/thy.2011.0104

The American Thyroid Association and American Assoc iation of Clinical Endocrinologists Hyperthyroidism and Other Causes of Thyrotoxicosis Guidelines: Viewpoints From Japan and Korea. Thyroid, 21(6):577-80. Yamashita S, Amino N, Shong YK. 2011. PubMed-ID: 21663418 http://dx.doi.org/10.1089/thy.2011.2106.ed1

Highlights of the Guidelines on the Management of H yperthyroidism and Other Causes of Thyrotoxicosis. Thyroid , 21(6):581-4. Medeiros-Neto G, Romaldini JH, Abalovich M. 2011. PubMed-ID: 21663419 http://dx.doi.org/10.1089/thy.2011.2106.ed2

The American Thyroid Association/American Associati on of Clinical Endocrinologists Guidelines for Hyperthyroidism and Other Causes of Thyrotoxicosis: a European Perspective. Thyroid, 21(6):585-91. Kahaly GJ, Bartalena L, Hegedus L. 2011. PubMed-ID: 21663420 http://dx.doi.org/10.1089/thy.2011.2106.ed3

Impact of Continuous Intraoperative Neuromonitoring on Autonomic Nervous System During Thyroid Surgery. Head Neck, 33(7):976-84. Ulmer C, Friedrich C, Kohler A, Rieber F, Basar T, Deuschle M, Thon KP, Lamade W. 2011. BACKGROUND: Continuous intraoperative neuromonitoring (CIONM) via vagal nerve stimulation (VNS) is a new option for recurrent laryngeal nerve (RLN) protection during thyroid surgery. The aim of this study was to evaluate the safety of VNS for CIONM and to assess its effects on the autonomic nervous system (ANS) through analyzing heart rate variability (HRV). METHODS: In a prospective, nonrandomized controlled study 5 patients received VNS for CIONM and 5 were operated on with conventional intermittent intraoperative neuromonitoring


(IONM). HRV was analyzed in accord with patient-specific reference values. RESULTS: VNS resulted in significantly altered ANS balance. Relative parasympathetic activity increased during VNS. Yet, no relevant cardiac arrhythmias or hemodynamic alterations were observed during VNS. CONCLUSION: HRV analysis revealed a distinct impact of VNS for CIONM on ANS balance. VNS caused parasympathetic predominance that was not countered by increased sympathetic activity. PubMed-ID: 21674672 http://dx.doi.org/10.1002/hed.21564

Preoperative Multidisciplinary Management of Airway Obstruction by Huge Goiter With Papillary Thyroid Cancer. Am Surg, 77(5):E91-E93. Yamaguchi S, Fujii T, Yajima R, Uchida N, Ide M, Tsutsumi S, Yamauchi H, Kigure W, Morita H, Suto T, Asao T, Kuwano H. 2011. PubMed-ID: 21679579

A Supraclavicular Approach to Thyroidectomy. Am Surg, 77(5):656-8. Yang YL, Lin BR, Pan YF, Zhang XH. 2011. PubMed-ID: 21679608

Clinical Relevance of Thyroglobulin Doubling Time i n the Management of Patients With Differentiated Thyroid Cancer. Thyroid, 21(7):691-2. Pacini F, Sabra MM, Tuttle RM. 2011. PubMed-ID: 21707434 http://dx.doi.org/10.1089/thy.2011.2107.ed1

Management of Recurrent/Persistent Papillary Thyroi d Carcinoma: Efficacy of the Surgical Option. J Clin Endocrinol Metab, 96(7):2038-9. Schuff KG. 2011. PubMed-ID: 21734006 http://dx.doi.org/10.1210/jc.2011-1663

Performing Contralateral Central Lymph Node Dissect ion in Papillary Thyroid Carcinoma: a Decision Approach. Thyroid, 21(8):873-7. Chae BJ, Jung CK, Lim DJ, Song BJ, Kim JS, Jung SS, Bae JS. 2011. BACKGROUND: Substantial controversy exists over the role of prophylactic neck dissection for patients with papillary thyroid carcinoma (PTC). We hypothesized that a therapeutic strategy of performing a routine intraoperative frozen section of the ipsilateral central lymph node (CLN) after elective ipsilateral CLN dissection (CLND) for all unilateral PTC and then performing a contralateral CLND if the frozen section is positive for malignancy would reduce morbidity compared to a therapeutic strategy of routine bilateral CLND. METHODS: In a group of 419 patients with PTC undergoing thyroidectomy during study the period, the 203 patients who had unilateral PTC and no evidence of adenopathy on ultrasonography were prospectively enrolled in our nonrandomized study that was performed between March 2009 and February 2010. Patients underwent a total thyroidectomy if tumor size was over 1 cm or extrathyroidal was detected on ultrasonography. Patients underwent a subtotal or near-total thyroidectomy if tumor size was <1 cm and additional benign tumor existed on contralateral lobe. There were 25 patients who had a unilateral CLND with a subtotal or near-total thyroidectomy, and 178 patients who underwent a unilateral or bilateral CLND with a total thyroidectomy. RESULTS: There was no difference in the rate of major complications between unilateral CLND group and bilateral CLND group. The rate of transient hypocalcemia was 31.8% in the unilateral CLND group and 45.7% in the bilateral CLND group (p = 0.084). The rate of voice change was 7.6% in the unilateral CLND group 4.3% in the bilateral CLND group (p = 0.438). The ratio of malignant to all nodes retrieved was 0.5/7.88 in the unilateral CLND group and 5.13/17.20 in the bilateral CLND group. There was 78.3% sensitivity and 100% specificity for frozen biopsy of ipsilateral CLN to predict contralateral CLN metastasis. A positive ipsilateral CLN frozen biopsy was significantly associated with contralateral CLN metastasis (p < 0.001), as was younger age (p = 0.002) and existence of extrathyroidal extension (p = 0.031), each on univariate analysis. CONCLUSIONS: In patients with unilateral PTC, routine ipsilateral CLND with intraoperative reading of the frozen section can be employed to assess the risk of contralateral CLN metastasis. This information should be of value in deciding whether to perform


contralateral CLND or not. PubMed-ID: 21745104 http://dx.doi.org/10.1089/thy.2010.0214

The Basis of Preoperative Vocal Fold Paralysis in a Series of Patients Undergoing Thyroid Surgery: the Preponderance of Benign Thyroid Disease. Thyroid, 21(8):867-72. Wang CC, Wang CP, Tsai TL, Liu SA, Wu SH, Jiang RS, Shiao JY, Su MC. 2011. BACKGROUND: Preoperative vocal fold paralysis (VFP) is thought to be rare in patients with benign thyroid disease (BTD). In contrast with cases of malignancy, in which the recurrent laryngeal nerve (RLN) should be severed, in patients with BTD and VFP the RLN can be preserved without threatening patients' lives. This study investigates the clinical features that enable identification of patients who have VFP associated with BTD. METHODS: Medical records of 187 consecutive patients who underwent thyroid surgery were retrospectively reviewed. The association between preoperative VFP and pathology (benign or malignant), clinical features, and treatment results of patients with BTD and VFP were analyzed. RESULTS: Of the 187 patients, 145 patients had BTD and 8 of these cases (5.52%) had preoperative unilateral VFP. The prevalence of BTD with VFP was 4.3% (8/187). The other 42 patients had malignant thyroid disease and 4 of these cases (9.52%) had preoperative unilateral VFP. None of the aforementioned VFP was caused by previous thyroidectomy or surgery to the neck. Although the relative risk of VFP in patients with thyroid malignancy was 1.726 (9.52%/5.52%), there was no significant association between VFP and malignancy. Of the eight patients with BTD, benign fine-needle aspiration cytology or frozen sections, goiter with a diameter larger than 5 cm, cystic changes, and significant radiologic tracheo-esophageal groove compression were the common findings. During thyroidectomy, the RLN was injured but repaired in three patients. Two events occurred in patients who had severe RLN adhesion to the tumor caused by thyroidectomy performed decades ago. Two of the five patients without nerve injury recovered vocal fold function. The overall VFP recovery rate for patients with BTD and VFP was 25% (2/8). CONCLUSIONS: Preoperative unilateral VFP is not uncommon in thyroid surgery. Obtaining information on laryngeal function is of extreme importance when planning surgery, especially contralateral surgery. Goiter with preoperative VFP is not necessarily an indicator of malignancy. Benign perioperative cytopathologic findings with typical radiographic compression strongly suggest that VFP is caused by BTD. If, during thyroidectomy, the RLN is carefully preserved, recovery of vocal fold function may still be possible. PubMed-ID: 21745108 http://dx.doi.org/10.1089/thy.2010.0280

Delayed Risk Stratification, to Include the Respons e to Initial Treatment (Surgery and Radioiodine Ablation), Has Better Outcome Predictivity in Diffe rentiated Thyroid Cancer Patients. Eur J Endocrinol, 165(3):441-6. Castagna MG, Maino F, Cipri C, Belardini V, Theodoropoulou A, Cevenini G, Pacini F. 2011. INTRODUCTION: After initial treatment, differentiated thyroid cancer (DTC) patients are stratified as low and high risk based on clinical/pathological features. Recently, a risk stratification based on additional clinical data accumulated during follow-up has been proposed. OBJECTIVE: To evaluate the predictive value of delayed risk stratification (DRS) obtained at the time of the first diagnostic control (8-12 months after initial treatment). METHODS: We reviewed 512 patients with DTC whose risk assessment was initially defined according to the American (ATA) and European Thyroid Association (ETA) guidelines. At the time of the first control, 8-12 months after initial treatment, patients were re-stratified according to their clinical status: DRS. RESULTS: Using DRS, about 50% of ATA/ETA intermediate/high-risk patients moved to DRS low-risk category, while about 10% of ATA/ETA low-risk patients moved to DRS high-risk category. The ability of the DRS to predict the final outcome was superior to that of ATA and ETA. Positive and negative predictive values for both ATA (39.2 and 90.6% respectively) and ETA (38.4 and 91.3% respectively) were significantly lower than that observed with the DRS (72.8 and 96.3% respectively, P<0.05). The observed variance in predicting final outcome was 25.4% for ATA, 19.1% for ETA, and 62.1% for DRS. CONCLUSIONS: Delaying the risk stratification of DTC patients at a time when the response to surgery and radioiodine ablation is evident allows to better define individual risk and to better modulate the subsequent follow-up. PubMed-ID: 21750043 http://dx.doi.org/10.1530/EJE-11-0466


Preoperative Serum Thyroglobulin Concentration Is a n Independent Predictive Factor of Malignancy in Follicular Neoplasms of the Thyroid Gland. J Surg Oncol, Petric R, Perhavec A, Gazic B, Besic N. 2011. BACKGROUND: A distinction between a benign follicular neoplasm (FN) and a malignant FN based entirely on cytologic examination of fine-needle aspiration biopsy is not possible. The aim of this retrospective study was to find predictive factors of carcinoma in patients with FN. METHODS: A chart review of 388 patients (314 females, 74 males; mean age 50 years, range 9-81 years) with FN, who were surgically treated between 1988 and 2009, was performed. Predictive factors for malignancy were identified by the chi-squared test and multivariate logistic regression. RESULTS: The histopathological diagnoses were carcinoma, adenoma, and benign goiter in 127 (33%), 126 (32%), and 135 (35%) patients, respectively. The independent predictors of malignancy as shown by multivariate logistic regression were age of patients (OR 1.88, P = 0.008), solitary tumor (OR 1.72, P = 0.037), and Tg concentration (OR 2.36, P = 0.001). Carcinoma was more common in patients younger than 45 years, with solitary tumor and with preoperative serum Tg concentration more than 400 ng/ml. CONCLUSIONS: The independent predictors of malignancy in FN were age of patients, solitary tumor, and preoperative Tg concentration. The determination of Tg concentration may be useful in the patients with FN in order to decrease the number of completion thyroidectomies. J. Surg. Oncol (c) 2011 Wiley-Liss, Inc. PubMed-ID: 21751218 http://dx.doi.org/10.1002/jso.22030

Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and Postpartum. Thyroid, 21(10):1081-125. Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, Nixon A, Pearce EN, Soldin OP, Sullivan S, Wiersinga W. 2011. PubMed-ID: 21787128 http://dx.doi.org/10.1089/thy.2011.0087

Ultrasonographically Detected Small Thyroid Bed Nod ules Identified After Total Thyroidectomy for Differentiated Thyroid Cancer Seldom Show Clinicall y Significant Structural Progression. Thyroid, 21(8):845-53. Rondeau G, Fish S, Hann LE, Fagin JA, Tuttle RM. 2011. BACKGROUND: High-resolution ultrasound (US) is the primary tool used to identify locoregional recurrences in differentiated thyroid cancer. Although small thyroid bed (TB) nodules are a commonly reported sonographic finding, their natural history, regardless of whether they are benign or malignant, has not been well characterized. This study was designed to determine the likelihood, magnitude, and rate of growth of small TB nodules identified on routine surveillance neck US after thyroidectomy for differentiated thyroid cancer as well as to identify ultrasonographic and clinical predictors of growth. METHODS: This retrospective review identified 191 patients with at least one TB nodule (</= 11 mm) on the first postoperative US performed at a comprehensive cancer center. Change in size of each TB nodule was determined using serial US studies over time. Clinicopathologic and sonographic characteristics were analyzed as possible predictors for growth of the TB nodules. RESULTS: Over a median clinical follow-up of 5 years, 9% (17/191) of patients had increase in size of at least one TB nodule. Median size of the TB nodules was 5 mm (range: 2-11 mm). Suspicious US features were seen in 63% (121/191) of patients with TB nodules identified on initial US and in 31% (21/67) of those with TB nodules detected on subsequent follow-up US. The rate of growth was 1.3 mm/year in those nodules showing an increase in size and thus demonstrated a significant increase in size only after several years of follow-up. The negative predictive values associated with the absence of any suspicious US features (0.97), the absence of abnormal cervical lymph nodes (0.94), and the lack of a rising serum thyroglobulin (0.93) provided clinically useful information regarding the likelihood that nodules would not increase in size. CONCLUSION: Most TB nodules do not show clinically significant growth over several years of follow-up. Thus, TB nodules can be followed up with cautious observation and serial ultrasonography using an approach similar to that recommended by the American Thyroid Association thyroid cancer guidelines for the management of small abnormal cervical lymph nodes. PubMed-ID: 21809914 http://dx.doi.org/10.1089/thy.2011.0011

Update on External Beam Radiation Therapy in Thyroi d Cancer. J Clin Endocrinol Metab, 96(8):2289-95. Brierley JD. 2011.


Surgery is the mainstay of treatment for thyroid cancer. The role for external beam radiotherapy (EBRT) as an adjuvant to surgery or as the primary therapy is established in anaplastic thyroid cancer but is controversial in differentiated thyroid cancer and uncertain in medullary thyroid cancer. This update reviews the recent reported success of combining EBRT with taxanes in anaplastic thyroid cancer. Also discussed are the recent reports from large single institutions that support the recommendations of the American and British Thyroid Associations on the use of EBRT in high-risk differentiated thyroid cancer. Further evidence on the role of EBRT in MTC is discussed. The important advances in the delivery of EBRT using intensity-modulated radiation and image-guided radiation that result in more accurate and potentially more effective radiation therapy with less toxicity are also discussed. PubMed-ID: 21816795 http://dx.doi.org/10.1210/jc.2011-1109

Approach to the Thyroid Cancer Patient With Bone Me tastases. J Clin Endocrinol Metab, 96(8):2296-307. Wexler JA. 2011. PubMed-ID: 21816796 http://dx.doi.org/10.1210/jc.2010-1996

Multiple Endocrine Abnormalities. Lancet, 378(9790):540. van Durme CM, Kisters JM, van PP, van Etten RW, Tervaert JW. 2011. PubMed-ID: 21821186 http://dx.doi.org/10.1016/S0140-6736(11)60831-3

Assessment of Time and Cost of Anesthesia With Vers us Without Recurrent Laryngeal Nerve Monitoring in Patients Undergoing Total Thyroidectomy. Am Surg, 77(8):158-9. Bailey CW, Crosby LD, Johnson B, Lokey JS. 2011. PubMed-ID: 21944499

Complete Rupture of the Inferior Thyroid Artery. Am Surg, 77(8):1107-9. Mittermair R, Strohmenger U, Rieger M, Pratschke J. 2011. PubMed-ID: 21944539

Transoral Thyroid and Parathyroid Surgery--Developm ent of a New Transoral Technique. Surgery, 150(1):108-15. Karakas E, Steinfeldt T, Gockel A, Schlosshauer T, Dietz C, Jager J, Westermann R, Sommer F, Richard HR, Exner C, Sesterhenn AM, Bartsch DK. 2011. BACKGROUND: Transluminal interventions via so-called natural orifices are gaining interest because they allow operative treatment without any skin incision. We previously described a transoral access for (para-)thyroid resection in pigs. To proceed with the first clinical trials, we evaluated the safety of the new technique. METHODS: Transoral hemithyroidectomies were performed on 10 living pigs using a special cervicoscope and conventional laparoscopic instruments. Follow-up examinations were carried out for 14 days and followed by autopsy, which included macroscopic evaluation, microbiologic investigations, and blood testing. In addition, refinement of the new technique was achieved by developing the techniques in 10 human cadavers. Finally, transoral parathyroidectomies were performed in 2 patients with primary hyperparathyroidism and a preoperatively localized parathyroid adenoma. RESULTS: All animal transoral hemithyroidectomies were performed without complications. Postoperatively, oral intake, weight gain, and white blood cell count remained normal. At autopsy, the access route, and operative field showed no signs of infection, and microbiologic swabs remained sterile. Based on these results, a transoral parathyroidectomy was performed successfully in 2 female patients with primary hyperparathyroidism; 1 patient experienced a transient palsy of the right hypoglossal nerve. CONCLUSION: Transoral parathyroid and thyroid operation is feasible; however, additional controlled clinical studies are required to evaluate the safety and success rates of this new technique. PubMed-ID: 21458014 http://dx.doi.org/10.1016/j.surg.2010.12.016


Thyroidectomy and Parathyroidectomy in Patients Wit h High Body Mass Index Are Safe Overall: Analysis of 26,864 Patients. Surgery, Buerba R, Roman SA, Sosa JA. 2011. BACKGROUND: Obesity is a national epidemic. Prior studies of the impact of body mass index (BMI) on surgical outcomes from cervical endocrine procedures have come from high-volume, single institutions. Our study characterizes the 30-day clinical and economic outcomes in patients with high BMI from a multi-institutional database. METHODS: Patients undergoing thyroidectomy or parathyroidectomy in the American College of Surgeons National Surgery Quality Improvement Program, 2005-2008 were categorized into 4 groups BMI based on: normal, overweight, obese, and morbidly obese. Overweight, obese, and morbidly obese patients were compared with patients with normal BMI using a chi(2) test and an analysis of variance. Multivariable linear/logistic regression models were used to adjust for preoperative risk factors. RESULTS: In all, 18,825 patients underwent thyroidectomy. Overweight, obese, and morbidly obese patients were more likely to have total thyroidectomy, substernal thyroids, general anesthesia, operations of greater duration, and an overall or wound complication (all P < .01). On a multivariable analysis, morbidly obese patients had an increased risk for urinary complications (P < .05); obese and morbidly obese patients had an increased risk for overall or wound complications (P < .01); overweight, obese, and morbidly obese patients had operations of greater duration (P < .05). In all, 8,039 patients underwent parathyroidectomy. Overweight, obese, and morbidly obese patients were more likely to have general anesthesia and operations of greater duration (all P < .01). On multivariable analysis, morbidly obese patients had operations of greater duration (P < .05) and more wound complications (P = .05). CONCLUSION: Patients with high BMI seem to require operations of greater duration and sustain more morbidity after cervical endocrine procedures than patients with normal BMI, but these differences may not be clinically significant. Thyroidectomy and parathyroidectomy can be performed safely, with appropriate surgical decision making. PubMed-ID: 21621238 http://dx.doi.org/10.1016/j.surg.2011.02.017


Parathyroid

Meta-Analyses A Meta-Analysis of Preoperative Localization Techni ques for Patients With Primary Hyperparathyroidism. Ann Surg Oncol, Cheung K, Wang TS, Farrokhyar F, Roman SA, Sosa JA. 2011. BACKGROUND: Reported accuracy of preoperative localization imaging for primary hyperparathyroidism (pHPT) varies. The purpose of this study is to determine the accuracy of ultrasound, sestamibi-single photon emission computed tomography (SPECT), and four-dimensional computed tomography (4D-CT) as preoperative localization strategies. METHODS: A meta-analysis was performed of studies investigating the accuracy of ultrasound, sestamibi-SPECT, and 4D-CT for preoperative localization in pHPT. Electronic databases were systematically searched, and two independent reviewers reviewed results using specific criteria. Study quality was assessed using a validated measure for diagnostic imaging studies. Study heterogeneity and pooled results were calculated. RESULTS: 43 studies met criteria for inclusion, and data were available for extraction in 19 ultrasound, 9 sestamibi-SPECT, and 4 4D-CT studies. Ultrasound had pooled sensitivity and positive predictive value (PPV) of 76.1% (95% CI 70.4-81.4%) and 93.2% (90.7-95.3%), respectively. Sestamibi-SPECT had pooled sensitivity and PPV of 78.9% (64-90.6%) and 90.7% (83.5-96.0%), respectively. Only two 4D-CT studies investigated patients undergoing initial parathyroidectomy. Results suggested sensitivity and PPV of 89.4% and 93.5%, respectively. CONCLUSIONS: Ultrasound and sestamibi-SPECT are similar in ability to preoperatively localize abnormal parathyroid glands in pHPT. Accuracy may be improved with 4D-CT; however, further investigation is required. Choice of preoperative imaging strategy depends on numerous patient, institutional, and economic factors of which the surgeon must be aware. PubMed-ID: 21710322 http://dx.doi.org/10.1245/s10434-011-1870-5

The Optimal Surgical Treatment for Primary Hyperpar athyroidism in MEN1 Patients: a Systematic Review. World J Surg, 35(9):1993-2005. Schreinemakers JM, Pieterman CR, Scholten A, Vriens MR, Valk GD, Rinkes IH. 2011. BACKGROUND: The optimal surgical approach for patients with primary hyperparathyroidism (pHPT) and multiple endocrine neoplasia 1 (MEN1) is controversial. We sought to determine the optimal type of surgery for pHPT in MEN1. METHODS: We collected data on clinical presentation, surgery, and follow-up for MEN1 patients with pHPT at the University Medical Center Utrecht and affiliated hospitals between 1967 and 2008. Furthermore, we performed a systematic review of the literature and meta-analysis. Surgical procedures were classified into less than subtotal (<SPTX) versus subtotal (SPTX) and total parathyroidectomy (TPTX). RESULTS: Fifty-two patients underwent primary surgery for pHPT, of which 29 had <SPTX, 17 SPTX, and 6 TPTX. Recurrent pHPT was most frequent after SPTX (65%) followed by <SPTX (59%). Persistent disease was most frequent after <SPTX (31%). Time to recurrence was 61 months longer after SPTX than after <SPTX. Although recurrent pHPT was not seen after TPTX, permanent hypoparathyroidism developed in 67% of these patients. The meta-analysis showed that after SPTX and TPTX, patients had the lowest risk of persistent and recurrent pHPT. TPTX had the highest risk of permanent hypoparathyroidism. Large noncomparative studies showed a low recurrence rate after SPTX and TPTX. CONCLUSION: We believe that SPTX is the best surgical therapy for pHPT in MEN1. MEN1 patients with pHPT should not be treated with <SPTX because of the unacceptable high rate of recurrent and persistent pHPT. Additionally, a thymectomy should routinely be performed in these patients. PubMed-ID: 21713580 http://dx.doi.org/10.1007/s00268-011-1068-9

Randomized controlled trials - None -


Other Articles Importance of Intraoperative Parathyroid Hormone Me asurement in the Diagnosis of Parathyroid Lipoadenoma. Head Neck, 33(6):917-9. Lee AY, Wang BY, Heller KS. 2011. BACKGROUND: Parathyroid lipoadenoma is an uncommon tumor that may be difficult to diagnose on intraoperative frozen section. Intraoperative parathyroid hormone (PTH) measurement is useful in assessing the adequacy of parathyroidectomy. This case demonstrates the value of intraoperative PTH measurement in recognizing a parathyroid lipoadenoma. METHODS AND RESULTS: A case of a 62-year-old woman with primary hyperparathyroidism in which intraoperative PTH measurement helped confirm the diagnosis of parathyroid lipoadenoma is presented. CONCLUSIONS: In patients with primary hyperparathyroidism, a significant decrease in intraoperative PTH confirms that an enlarged parathyroid with normal to low cellularity containing abundant fat is a lipoadenoma and that further exploration is not necessary. PubMed-ID: 20091680 http://dx.doi.org/10.1002/hed.21339

Results of Surgery for Sporadic Primary Hyperparath yroidism in Patients With Preoperatively Negative Sestamibi Scintigraphy and Ultrasound. Langenbecks Arch Surg, 396(1):83-90. Bergenfelz AO, Wallin G, Jansson S, Eriksson H, Martensson H, Christiansen P, Reihner E. 2011. PURPOSE: The purpose of this study is to investigate the results of first-time surgery for sporadic primary hyperparathyroidism (pHPT) in patients with preoperatively negative sestamibi scintigraphy and ultrasound. METHODS: Data were gathered prospectively in a multicenter database for quality control in parathyroid surgery. Between 2004 and 2008, 3,158 patients underwent first-time surgery for sporadic pHPT. A total of 984 patients were subjected to preoperative localization with ultrasound and sestamibi scintigraphy, and in 173 patients, both investigations were negative. Intraoperative findings and early outcome are reported. RESULTS: One hundred and fifty-five of 173 patients underwent bilateral neck exploration. The median weight of excised parathyroid tissue was 350 mg. In 23 patients (13.3%), the exploration was negative. A total of 112 patients (64.7%) had a histological diagnosis of parathyroid adenoma and 38 patients (22%) had multiglandular disease. Six weeks after operation, 164 patients were available for analysis, and 30 patients (18%) had persistent pHPT. The risk for persistent pHPT increased for patients with few intraoperatively identified (p = 0.001) and excised (p = 0.024) parathyroid glands. Patients operated with intraoperative parathyroid hormone (iOPTH) had lower risk for persistent pHPT 7/79 (9%) compared with 23/85 patients (27%) operated without iOPTH (p = 0.003). CONCLUSIONS: Negative localization with sestamibi and ultrasound in pHPT infers a highly selected patient population with small parathyroid adenomas, an alarmingly high rate of negative exploration, and an increased risk for persistent disease. The use of iOPTH influences cure rate favorably. PubMed-ID: 21061130 http://dx.doi.org/10.1007/s00423-010-0724-0

To Supplement or Not to Supplement: a Cost-Utility Analysis of Calcium and Vitamin D Repletion in Patients After Thyroidectomy. Ann Surg Oncol, 18(5):1293-9. Wang TS, Cheung K, Roman SA, Sosa JA. 2011. BACKGROUND: Postoperative hypocalcemia is the most common complication after thyroidectomy; prevention and treatment remain areas of ongoing debate. The purpose of this study was to determine the incremental cost utility of routine versus selective calcium and vitamin D supplementation after total or completion thyroidectomy. METHODS: A cost-utility analysis using a Markov decision model was performed for a hypothetical cohort of adult patients after thyroidectomy. Routine or selective supplementation of oral calcium carbonate, vitamin D (calcitriol), and intravenous calcium gluconate, when required, was used. Selective supplementation was determined by serum intact parathyroid hormone levels. The incremental cost utility, measured in U.S. dollars per quality-adjusted life-year (QALY), was calculated. RESULTS: In the base-case analysis, the cost of routine supplementation was $102 versus $164 for selective supplementation. Patients in the routine arm gained 0.002 QALYs compared to patients in the selective arm (0.95936 QALYs vs. 0.95725 QALYs). At the population level, this translates into a savings of $29,365/QALY (95% confidence interval, -$66,650 to -$1,772) for routine supplementation. Sensitivity analyses demonstrated that the model was most sensitive to the utility of the hypocalcemic state, postoperative rates of hypocalcemia, and cost of serum parathyroid hormone testing. CONCLUSIONS: Routine oral calcium and calcitriol supplementation in patients after thyroidectomy seems to be less expensive and results in higher patient utility than selective supplementation. Surgeons who have very low


rates of hypocalcemia in their patients may benefit less from routine supplementation. PubMed-ID: 21088914 http://dx.doi.org/10.1245/s10434-010-1437-x

Common Locations of Parathyroid Adenomas. Ann Surg Oncol, 18(4):1047-51. Moreno MA, Callender GG, Woodburn K, Edeiken-Monroe BS, Grubbs EG, Evans DB, Lee JE, Perrier ND. 2011. BACKGROUND: We have developed a nomenclature system that succinctly specifies the locations of parathyroid adenomas in the neck. We report our experience using the system in a large, contemporary cohort of patients. METHODS: A prospective, endocrine surgery database at a single, tertiary care center was retrospectively analyzed. We reviewed the records of 271 patients operated on for sporadic primary hyperparathyroidism between January 2006 and May 2008 and analyzed the effect of adenoma location at operative intervention and outcome. RESULTS: Adenomatous gland locations were classified intraoperatively as: A (adherent to posterior thyroid capsule) in 12.5% of cases; B (tracheoesophageal groove) in 17.3%; C TE groove but (close to clavicle) in 13.7%; D (directly over the recurrent laryngeal nerve) in 12.2%; E (easy to identify, inferior thyroid pole) in 25.8%; F (fallen into thymus) in 7.4%; and G gauge (within thyroid gland) in 0.4%. More than one enlarged gland was present in 10.7% of patients and usually involved coexistence of enlarged types A and E glands. Type F glands were associated with a longer mean operative time (p = 0.0487) and type E glands with a higher rate of outpatient surgery (p = 0.0195). At 6 months from the surgery, 94.5% of the patients were normocalcemic. CONCLUSIONS: Our nomenclature system provides a simple way to describe the locations of parathyroid adenomas. Type E adenomas were associated with a higher rate of outpatient surgery and type F adenomas with a longer operative time. Biochemical cure rates were comparable for all locations of single adenomas. PubMed-ID: 21104031 http://dx.doi.org/10.1245/s10434-010-1429-x

Durability of Focused Minimally Invasive Parathyroi dectomy in Young Patients With Sporadic Primary Hyperparathyroidism. Ann Surg Oncol, 18(5):1290-2. Oucharek JJ, O'Neill CJ, Suliburk JW, Sywak MS, Delbridge LW, Sidhu SB. 2011. BACKGROUND: Historically, multigland hyperplasia was believed to be the predominant cause of primary hyperparathyroidism (PHPT) in young patients, and hence a relative contraindication for minimally invasive parathyroidectomy. Recent studies, however, demonstrate that the most common aetiology across all age groups is a solitary functioning adenoma. The aim of this study was to compare long-term outcomes in young patients (</= 45 years), especially those under 30 years of age, with their older counterparts (> 45 years) following focused minimally invasive parathyroidectomy (FMIP). MATERIALS AND METHODS: Patients </= 45 years who underwent FMIP between January 1999 and December 2007 were identified from an endocrine surgery database and compared with a matched control group of patients > 45 years old also undergoing FMIP within that time period. The patients' most recent calcium levels (>/= 6 months postoperatively) were examined to establish recurrence rates. Recurrence was defined as an elevation of serum calcium more than 6 months after surgery following initial postsurgical normocalcemia. RESULTS: A total of 117 patients </= 45 years and 160 patients > 45 years who underwent FMIP were examined. Follow-up calcium levels were available for 72% of patients. The median length of follow-up was 46 months. No recurrences were identified in both the younger and older cohort of patients; therefore, no statistically significant difference in rates of recurrence could be determined between age groups. CONCLUSION: Recurrence of PHPT following FMIP is rare with no evidence of a higher incidence in younger patients. FMIP can be safely offered to young patients as a long-term durable treatment option. PubMed-ID: 21108046 http://dx.doi.org/10.1245/s10434-010-1417-1

4D Parathyroid CT As the Initial Localization Study for Patients With De Novo Primary Hyperparathyroidism. Ann Surg Oncol, 18(6):1723-8. Starker LF, Mahajan A, Bjorklund P, Sze G, Udelsman R, Carling T. 2011. BACKGROUND: Preoperative localization of parathyroid tumors of primary hyperparathyroidism (pHPT) is required for minimally invasive parathyroidectomy (MIP). Parathyroid four-dimensional computed tomography (4DCT) has mainly been used as an adjunct to other imaging modalities in the remedial setting. 4DCT was evaluated as the initial localization study in de novo patients with pHPT. MATERIALS AND METHODS: A total of


87 consecutive patients underwent parathyroidectomy for pHPT from August 2008 to November 2009. 4DCT was introduced as the preferred imaging modality instead of sestamibi with SPECT (SeS) in April 2009. Results of the imaging studies [4DCT, SeS, and ultrasonography (US)], operative and, pathologic findings, and biochemical measurements were evaluated. RESULTS: In this study, 84% of patients (73 of 87) underwent an US, 59.8% (52 of 87) a SeS, and 38.0% (33 of 87) had a 4DCT. 4DCT had improved sensitivity (85.7%) over SeS (40.4%) and US (48.0%) to localize parathyroid tumors to the correct quadrant of the neck (P < 0.005) as well as to localize (lateralize) the parathyroid lesions to one side of the neck (93.9% for 4DCT vs. 71.2% for US and 61.5% for SeS; P < 0.005). 4DCT correctly predicted multiglandular disease (MGD) in 85.7% (6 of 7) patients, whereas US and SeS were unable to detect MGD in any case. All patients achieved cure based on intraoperative parathyroid hormone (PTH) measurements and normalization of intact PTH and S-Ca during follow-up. CONCLUSIONS: 4DCT provides significantly greater sensitivity than SeS and US for precise localization of parathyroid tumors of pHPT. Additionally, it correctly predicted MGD in a majority of patients. PubMed-ID: 21184187 http://dx.doi.org/10.1245/s10434-010-1507-0

Large Parathyroid Tumors Have an Increased Risk of Atypia and Carcinoma. Am J Surg, 202(2):146-50. O'Neal P, Mowschenson P, Connolly J, Hasselgren PO. 2011. BACKGROUND: Risk for atypia and carcinoma in large parathyroid tumors is not known. Atypia and carcinoma were determined in small (<2 g) and large (>/=2 g) tumors in patients undergoing parathyroidectomy for primary hyperparathyroidism. METHODS: The study was a retrospective analysis of a 5-year prospective database. Tumor weight, histopathology, age, gender, calcium, and parathyroid hormone levels were registered. Patients with 4-gland disease were not included. RESULTS: Among 353 parathyroid tumors, 313 weighed <2 g and 40 weighed >/=2 g. There was no difference in age between groups. Patients with large tumors were more frequently men and had higher calcium and parathyroid hormone levels. Atypia was found in 4 of 313 (1.3%) and 7 of 40 (17.5%) small and large tumors, respectively (P < .05). Corresponding figures for carcinoma were 1 of 313 (.3%) and 2 of 40 (5.0%) (P < .05). CONCLUSIONS: Large parathyroid tumors have increased risk for atypia and carcinoma. Even so, most large parathyroid tumors are benign. PubMed-ID: 21256474 http://dx.doi.org/10.1016/j.amjsurg.2010.06.003

Vitamin D and Hyperparathyroidism in Obesity. J Clin Endocrinol Metab, 96(5):1320-6. Grethen E, McClintock R, Gupta CE, Jones R, Cacucci BM, Diaz D, Fulford AD, Perkins SM, Considine RV, Peacock M. 2011. BACKGROUND: Low vitamin D status and hyperparathyroidism occur in obesity and may be involved in pathogenesis of obesity-associated comorbid conditions. AIMS: Our aims were to determine in obesity whether there was vitamin D insufficiency, assessed by serum 25-hydroxyvitamin D (s25D) and serum PTH (sPTH) and whether it related to comorbid conditions. METHODS: We conducted a case-control study of 48 women having bariatric surgery and 50 healthy women frequency matched for race, age, year, and season of study. Height, weight, s25D, sPTH, serum 1,25-dihydroxyvitamin D (s1,25D), serum bone alkaline phosphatase, serum cross-linked N-telopeptides of type 1 collagen, and serum calcium, phosphate, creatinine, glucose, and insulin were measured, and comorbid conditions were documented from patient files. RESULTS: Weight (140 vs. 76 kg, P < 0.001), sPTH (44.4 vs. 25.6 pg/ml, P < 0.001), s1,25D (39 vs. 24 pg/ml, P < 0.001), serum bone alkaline phosphatase (19 vs. 12 ng/ml, P < 0.001), serum cross-linked N-telopeptides of type 1 collagen (9.6 vs. 7.9 nm bone collagen equivalents, P = 0.007), serum phosphate (3.45 vs. 3.24 mg/dl, P = 0.043), and serum creatinine (1.05 vs. 0.87 mg/dl, P < 0.001) were higher, and s25D (16 vs. 23 ng/ml, P <.001) was lower in bariatric-surgery women than control women. s25D was lower in bariatric-surgery women than controls in summer (17 vs. 26 ng/ml, P < 0.0001) but not winter (15 vs. 18 ng/ml, P > 0.2). Multiple regression analysis demonstrated that weight predicted s25D (P < 0.001) and sPTH (P = 0.001), but s25D did not predict sPTH or the presence of comorbid conditions except for osteoarthritis. CONCLUSION: Women having bariatric surgery had lower s25D and higher sPTH. The major determinant of s25D and sPTH was weight. Hyperparathyroidism in obesity did not indicate vitamin D insufficiency. Low s25D was not associated with comorbid conditions, apart from osteoarthritis. PubMed-ID: 21325456 http://dx.doi.org/10.1210/jc.2010-2202


Prevalence of Primary Hyperparathyroidism and Impac t on Bone Mineral Density in Elderly Men: MrOs Sweden. World J Surg, 35(6):1266-72. Siilin H, Lundgren E, Mallmin H, Mellstrom D, Ohlsson C, Karlsson M, Orwoll E, Ljunggren O. 2011. BACKGROUND: Age and sex are of importance in the development of primary hyperparathyroidism (PHPT), and the disease is most common in postmenopausal women. Skeletal complications are well known at an advanced stage of PHPT, although the impact on bone mineral density (BMD) is evident in patients with mild disease. This study examines the prevalence of PHPT in elderly men and its impact on BMD. METHODS: Calcium homeostasis and BMD, measured by dual X-ray absorptiometry, were evaluated in 3014 men ages 69 to 81 years in the MrOS-Sweden cohort. Individuals with a low glomerular filtration rate (<21 ml/min/1.73 m2) and vitamin D deficiency (<50 nmol/l) were excluded. Among the remaining subjects, PHPT was assumed in subjects with above-normal albumin-adjusted serum (s)-calcium and plasma intact parathyroid hormone (p-iPTH) levels (PHPT group). BMD was compared between the PHPT group and men without PHPT. Subjects with inappropriately elevated iPTH (IEP group), based on both s-calcium (2.34 mmol/l) and iPTH (4.24 pmol/l) levels being above the median level, were compared to the rest of the cohort. RESULTS: The prevalence of PHPT was estimated to be 0.73%. The mean BMD in the total hip and femoral neck was lower in the PHPT group than in the PHPT controls. Significantly lower BMD (p<0.05) was seen in the IEP group (total hip and lumbar spine). CONCLUSIONS: Elderly men appear to have a lower prevalence of PHPT than women at the same age. The impact of disturbed calcium homeostasis on BMD was also evident in this population group. PubMed-ID: 21445668 http://dx.doi.org/10.1007/s00268-011-1062-2

Cinacalcet Treatment of Primary Hyperparathyroidism . Int J Endocrinol, 2011:415719. Rothe HM, Liangos O, Biggar P, Petermann A, Ketteler M. 2011. Although parathyroidectomy remains the only curative approach to most primary hyperparathyroidism cases, medical treatment with cinacalcet HCl has been proven to be a reasonable alternative for several patient subgroups. Cinacalcet almost always controls hypercalcemia and hypophosphatemia sufficiently. PTH levels are lowered, and cognitive parameters improve. While an increase in bone mineral density DEXA scan scores was not demonstrated in cinacalcet trials, the same applies to more than half of patients after parathyroidectomy. Medical therapy should be first choice in patients with hyperplasia in all glands rather than an isolated adenoma (10-15%), patients with persisting HPT following unsuccessful surgery or inoperable cases due to comorbidities, and patients detected in lab screens for hypercalcemia before developing symptoms who should be treated early but are usually reluctant to undergo surgery. Nephrolithiasis was not found to occur more frequently in cinacalcet trial groups, but urine calcium excretion as one major risk factor of this complication of primary HPT may increase on cinacalcet. Patients carrying the rs1042636 polymorphism of the calcium-sensing receptor gene respond more sensitively to cinacalcet and have a higher risk of calcium stone formation. Cinacalcet is usually administered twice daily but three or four doses per day should be discussed to mimic the beneficial pulsatile PTH-pattern. PubMed-ID: 21461394 http://dx.doi.org/10.1155/2011/415719

Surgeon-Performed Ultrasound Is Superior to 99Tc-Se stamibi Scanning to Localize Parathyroid Adenomas in Patients With Primary Hyperparathyroidi sm: Results in 516 Patients Over 10 Years. J Am Coll Surg, 212(4):522-9. Untch BR, Adam MA, Scheri RP, Bennett KM, Dixit D, Webb C, Leight GS, Jr., Olson JA, Jr. 2011. BACKGROUND: Surgeon-performed cervical ultrasound (SUS) and 99Tc-sestamibi scanning (MIBI) are both useful in patients with primary hyperparathyroidism (PHPT). We sought to determine the relative contributions of SUS and MIBI to accurately predict adenoma location. STUDY DESIGN: We performed a database review of 516 patients undergoing surgery for PHPT between 2001 and 2010. SUS was performed by 1 of 3 endocrine surgeons. MIBI used 2-hour delayed anterior planar and single-photon emission computerized tomography images. Directed parathyroidectomy was performed with extent of surgery governed by intraoperative parathyroid hormone decline of 50%. RESULTS: SUS accurately localized adenomas in 87% of patients (342/392), and MIBI correctly identified their locations in 76%, 383/503 (p < 0.001). In patients who underwent SUS first, MIBI provided no additional information in 92% (144/156). In patients who underwent MIBI first, 82% of the time (176/214) SUS was unnecessary (p = 0.015). In 32 patients SUS was falsely negative. The reason for these included gland location in either the deep tracheoesophageal groove (n = 9) or the thyrothymic ligament below the clavicle (n = 5), concurrent thyroid goiter (n = 4), or thyroid cancer (n = 1). In 13 cases, the adenoma was located in a normal ultrasound-accessible location but was missed by the preoperative exam. In the 32


ultrasound false-negative cases, MIBI scans were positive in 21 (66%). Of the 516 patients, 7.6% had multigland disease. Persistent disease occurred in 4 patients (1%) and recurrent disease occurred in 6 (1.2%). CONCLUSIONS: When performed by experienced surgeons, SUS is more accurate than MIBI for predicting the location of abnormal parathyroids in PHPT patients. For patients facing first-time surgery for PHPT, we now reserve MIBI for patients with unclear or negative SUS. PubMed-ID: 21463783 http://dx.doi.org/10.1016/j.jamcollsurg.2010.12.038

Benign Familial Hypocalciuric Hypercalcemia. Endocr Pract, 17 Suppl 1:13-7. Varghese J, Rich T, Jimenez C. 2011. OBJECTIVE: To review the pathophysiology, clinical features, diagnosis, and management options for benign familial hypocalciuric hypercalcemia. METHODS: We present a systematic summary of benign familial hypocalciuric hypercalcemia after review of the current available literature. RESULTS: Benign familial hypocalciuric hypercalcemia is an autosomal dominant condition characterized by lifelong hypercalcemia, relative hypocalciuria, and inappropriately elevated parathyroid hormone. It is caused by a loss-of-function mutation in the calcium-sensing receptor gene (CASR). Benign familial hypocalciuric hypercalcemia is important clinically because it can be difficult to distinguish from primary hyperparathyroidism. It is a benign condition, and affected patients should be advised against parathyroidectomy. The incidence of complications associated with primary hyperparathyroidism, like osteopenia and nephrolithiasis, is not increased in persons with benign familial hypocalciuric hypercalcemia, and the rates are similar to those in the general population. Rarely, a severe form of this disease, namely neonatal severe primary hyperparathyroidism is seen in infants with homozygous CASR mutations. CONCLUSIONS: Benign familial hypocalciuric hypercalcemia is a small but important cause of hypercalcemia, especially in the younger population. Hypercalcemia persists after subtotal parathyroidectomy. It is important to diagnose this condition, not only in the index case but also in family members, because these patients should be advised against surgical intervention. PubMed-ID: 21478088 http://dx.doi.org/10.4158/EP10308.RA

Frequency of Ectopic and Supernumerary Intrathymic Parathyroid Glands in Patients With Renal Hyperparathyroidism: Analysis of 461 Patients Under going Initial Parathyroidectomy With Bilateral Cervical Thymectomy. World J Surg, 35(6):1260-5. Schneider R, Waldmann J, Ramaswamy A, Fernandez ED, Bartsch DK, Schlosser K. 2011. BACKGROUND: The frequency of intrathymic parathyroid glands (IPGs) in patients undergoing parathyroidectomy for renal hyperparathyroidism (rHPT) varies considerably between 14.8% and 45.3%. Total parathyroidectomy with autotransplantation and subtotal parathyroidectomy are the most accepted surgical procedures to treat patients with rHPT. However, routine bilateral cervical thymectomy (BCT) is still discussed, although controversially. METHODS: From a prospective database of patients who underwent parathyroid surgery for rHPT between 1975 and 2009, patients with routine BCT at initial PTX were further analyzed regarding the frequency of ectopic and supernumerary IPGs. Duration of hemodialysis and stage of chronic kidney disease were correlated with the frequency of supernumerary IPGs to elucidate a potential role of long-standing proliferation stimuli to any surplus parathyroid tissue. RESULTS: Initial parathyroidectomy with BCT was performed in 461 patients. IPGs were resected in 205 of them (44.5%). They were ectopic in 181 (39.3%) and supernumerary in 30 patients (6.5%). The frequency of supernumerary IPGs in patients on permanent hemodialysis was 7.4% (29/392), 3.9% (1/26) in predialysis patients, and 0% (0/43) in patients after successful kidney transplantation. This differences reached no statistical significance. CONCLUSIONS: BCT is essential in patients with fewer than four parathyroid glands identified at typical positions. Because of the low frequency of supernumerary IPGs and a suspected low proliferation stimulus, the relevance of BCT after resection of four glands in predialysis patients and those after successful kidney transplantation must be questioned. Nevertheless, routine BCT seems to be acceptable and can be recommended in patients on permanent hemodialysis not awaiting kidney transplantation until proven otherwise by prospective trials. PubMed-ID: 21479685 http://dx.doi.org/10.1007/s00268-011-1079-6

Intrathyroid Parathyroid Adenoma: Incidence and Loc ation--the Case Against Thyroid Lobectomy. Otolaryngol Head Neck Surg, 144(6):867-71. Goodman A, Politz D, Lopez J, Norman J. 2011. OBJECTIVE: It has been taught that a missing parathyroid adenoma can be within the thyroid. Therefore, thyroid


lobectomy is appropriate when an adenoma cannot be found. Unfortunately, this technique is often futile. The purpose of this study is to examine the frequency of unsuccessful thyroid lobectomy in parathyroid surgery and to look at the true incidence and location of intrathyroid parathyroid adenomas (iT-PAs). STUDY DESIGN: A retrospective chart review of 11,163 patients undergoing parathyroid surgery identifying the location of more than 40,000 parathyroid glands. SETTING: A tertiary care center specializing in parathyroid surgery. SUBJECTS AND METHODS: A total of 1163 reoperations for persistent primary hyperparathyroidism (PHPT) were examined for the incidence and outcomes of thyroid lobectomy performed to find iT-PA. A second study examined 10,000 patients undergoing first-time parathyroidectomy to classify the location and incidence of iT-PA. RESULTS: Thyroid lobectomy had been previously unsuccessfully performed in 77% cases of PHPT undergoing reoperation. Two or fewer glands were found in 82% prior to lobectomy. The adenoma was subsequently found on the lobectomy side in 64% and on the opposite side in 36%. True iT-PA occurred in only 0.7% of 10,000 primary cases. Another 1.2% were closely adherent to or partially within the thyroid substance. The most common location was the lower lateral quadrant of the thyroid. CONCLUSION: The incidence of true iT-PA is less than 1%, occurring in predictable locations. Thyroid lobectomy for a missing parathyroid adenoma is typically unsuccessful and should only rarely, if ever, be performed. PubMed-ID: 21493318 http://dx.doi.org/10.1177/0194599811400366

What Is the Added Benefit of Cervical Ultrasound to (99m)Tc-Sestamibi Scanning in Primary Hyperparathyroidism? Ann Surg Oncol, 18(10):2907-11. Adler JT, Chen H, Schaefer S, Sippel RS. 2011. BACKGROUND: Minimally invasive parathyroidectomy for primary hyperparathyroidism depends on accurate preoperative imaging, which is traditionally accomplished by (99m)Tc-sestamibi scanning. Cervical ultrasound is gaining in use, but it is unclear how much information it adds to the routine use of (99m)Tc-sestamibi scans. METHODS: A prospectively maintained database of patients undergoing parathyroidectomy for primary hyperparathyroidism was queried, and the utility of cervical ultrasound in preoperative planning was analyzed. RESULTS: Between July 2002 and November 2009, 310 patients with primary hyperparathyroidism underwent both (99m)Tc-sestamibi and ultrasound imaging. Ultrasound added new information to (99m)Tc-sestamibi in 43 patients (14%) by finding either the correct enlarged gland (n = 40, 88%) or additional enlarged glands (n = 5, 12%). Ultrasound correctly localized glands in 38 of 85 (45%) patients with a negative (99m)Tc-sestamibi, allowing for a minimally invasive parathyroidectomy in those patients. However, in the 206 patients (66%) who had a 1-gland positive (99m)Tc-sestamibi, ultrasound only added information for 8 patients (4%). When compared with radiology-performed ultrasound, surgeon-performed ultrasound was successful in localizing additional glands in 27 (15%) versus 17 patients (10%) (P < 0.001). CONCLUSIONS: Ultrasound led to additional localization information in 14% of patients, although this benefit was less in patients with a clearly positive 1-gland (99m)Tc-sestamibi scan. Cervical ultrasound provides added benefit to (99m)Tc-sestamibi scanning in patients with primary hyperparathyroidism, but its greatest utility is when performed by a surgeon in patients with a negative (99m)Tc-sestamibi scan. PubMed-ID: 21509629 http://dx.doi.org/10.1245/s10434-011-1724-1

1000 Minimally Invasive Parathyroidectomies Without Intra-Operative Parathyroid Hormone Measurement: Lessons Learned. ANZ J Surg, 81(5):362-5. Suliburk JW, Sywak MS, Sidhu SB, Delbridge LW. 2011. BACKGROUND: Minimally invasive parathyroidectomy (MIP) has become the procedure of choice in the treatment of primary hyperparathyroidism where a single adenoma can be localized preoperatively. The role for intra-operative parathyroid hormone measurement (IOPTH) is controversial. Some experts recommend that IOPTH is a mandatory requirement for successful MIP while others state that the technique is not needed. We reviewed 10 years of MIP in a single unit without the use of IOPTH in order to examine causes of failure. METHODS: This study is a retrospective review of the University of Sydney Endocrine Surgery Database from May of 1998 to August of 2008. The database was queried for MIPs performed as well as for failed operations. Patient record analysis was completed to determine the reason for failure of the operation. RESULTS: In the period January 1998 to August 2008, a total of 2343 parathyroidectomy procedures were performed. Of these, 1020 were MIPs with 23 (2.2%) failures. One patient was found to have benign familial hypercalcemia, whereas five were lost to follow-up. Reasons for failure in the remaining 17 patients were: 10 patients (59%) were found to have double adenomas, 3 (17%) patients with hyperplasia and 4 (24%) patients with single gland disease were missed at initial operation. All 17 were cured on repeat exploration. CONCLUSION: MIP can be performed


safely and with 98% success without the need for IOPTH. The most common cause of failure after MIP is an occult double adenoma. Given that repeat sestamibi scan correctly identifies persistent disease in most cases, consideration can be given to MIP as a choice of procedure for repeat operation. PubMed-ID: 21518187 http://dx.doi.org/10.1111/j.1445-2197.2010.05488.x

Nonendocrine Cancers Associated With Benign and Mal ignant Parathyroid Tumors. J Clin Endocrinol Metab, 96(7):E1108-E1114. Fallah M, Kharazmi E, Sundquist J, Hemminki K. 2011. CONTEXT: There are limited reliable epidemiological data concerning whether individuals with benign/malignant parathyroid tumor are at an elevated risk of developing nonendocrine malignancies or vice versa. OBJECTIVE: The objective of the study was to quantify these risks, especially risk of parathyroid tumors after other cancers. DESIGN: This was a population-based retrospective cohort study. PARTICIPANTS: Participants included the Swedish Family-Cancer Database (1958-2008; 11,697,301 individuals; 1,128,735 survivors of first primary cancers including 12,037 patients with parathyroid adenoma and 83 parathyroid adenocarcinoma). MAIN OUTCOME MEASURE: Standardized incidence ratios (SIR) were adjusted for age; sex; period; residential area; socioeconomic status; and history of hospitalization for obesity, alcoholism, or chronic obstructive pulmonary disease. RESULTS: Nonendocrine cancer sites with significantly increased risk after parathyroid adenoma were small intestine (SIR 2.3), blood (polycythemia vera 2.0), kidney (1.8), nervous system (1.6), skin (melanoma 1.4), and breast (women 1.2). Risk of parathyroid adenoma significantly increased after polycythemia vera (3.9) and malignancy in small intestine (3.5), kidney (2.8), nervous system (2.0), prostate (1.5), skin (melanoma 1.5), bladder (1.4), and breast (women 1.2). Twelve cases of parathyroid adenocarcinoma showed significantly higher risk after other tumors (2.4), especially after thyroid cancer (46.6) and parathyroid adenoma (27.3) but not vice versa in 11 cancer survivors. CONCLUSIONS: Parathyroid adenoma can be a risk factor for parathyroid adenocarcinoma; polycythemia vera; melanoma; and small intestine, kidney, nervous system and breast cancers. Further studies are suggested to find underlying mechanisms for these elevated risks, especially for increased risk of parathyroid tumor in patients with melanoma polycythemia vera, or malignancy in small intestine, kidney, nervous system, bladder, prostate, or breast. PubMed-ID: 21525164 http://dx.doi.org/10.1210/jc.2011-0099

Normal PTH Levels in Primary Hyperparathyroidism: S till the Same Disease? Ann Surg Oncol, Amin AL, Wang TS, Wade TJ, Yen TW. 2011. PURPOSE: Previous studies have suggested that primary hyperparathyroidism (pHPT) with only normal parathyroid hormone (PTH) levels is a milder, less symptomatic form of pHPT. This study investigates symptoms, laboratory values, imaging, and outcomes of sporadic pHPT patients with normal PTH values. METHODS: We reviewed our prospectively collected database of 861 patients with sporadic pHPT who underwent parathyroidectomy between December 1999 and June 2010. Patients with only normal PTH values for 6 months before surgery were compared to a randomized control group of sporadic pHPT patients with elevated PTH, matched 1:2 for age and gender. RESULTS: Fifty-eight (7%) patients had only normal PTH values within 6 months of surgery. The mean PTH was 55.1 pg/ml in the normal PTH group and 151.3 pg/ml in the control group (n = 116). There was no difference in preoperative calcium values, subjective symptoms, bone health, or the frequency of single-gland disease (SGD; 88% vs. 91%) between the two groups, but the normal PTH group had higher preoperative vitamin D values (30.8 vs. 21.4 ng/ml; P < 0.001), smaller adenomas (405 vs. 978 mg, P < 0.001), and more frequently underwent bilateral neck exploration (57% vs. 49%). There was a trend toward lower sensitivity of preoperative imaging in the normal PTH group. CONCLUSIONS: Patients with pHPT and either elevated or normal PTH levels present with similar symptoms and calcium levels. The majority of patients with normal PTH have SGD, although adenomas are smaller. This may explain why patients with normal PTH values have less sensitive imaging and more frequently require four-gland exploration. PubMed-ID: 21537864 http://dx.doi.org/10.1245/s10434-011-1744-x

Robotic-Assisted Parathyroidectomy: a Feasibility S tudy. Otolaryngol Head Neck Surg, 144(6):859-66. Tolley N, Arora A, Palazzo F, Garas G, Dhawan R, Cox J, Darzi A. 2011. OBJECTIVE: Targeted parathyroidectomy is the gold standard for localized parathyroid disease. A robotic-assisted approach has not been investigated. The aim was to assess the feasibility of a robotic technique that avoids a neck scar. STUDY DESIGN: Feasibility study. SETTING: Tertiary referral center. SUBJECTS AND


METHODS: Eleven patients with primary hyperparathyroidism were prospectively evaluated. Triple modality concordant localization was a prerequisite. All patients underwent robotic-assisted parathyroidectomy (RAP). Outcome variables assessed were operative time, voice change, biochemical cure, and histopathological confirmation. Patient-reported outcome measures (PROMs) included subjective assessment of pain and scar cosmesis, Voice Handicap Index 2, and EQ-5D quality-of-life assessment. Mean follow-up was 6 months (range, 3-12 months). RESULTS: The parathyroid adenoma was successfully excised in all cases with negligible blood loss (<5 mL). There was 1 conversion. There was no voice change in any case. Robot docking time plateaued to 10 minutes after 8 cases. Mean exposure and console times (31 and 51 minutes, respectively) were affected by body habitus. The mean visual analog scale for scar cosmesis was 75% on the first postoperative day, improving to 92% at 6 months and 95% at 1 year. Pain scores decreased to 8% at 2 weeks. All 5 EQ-5D quality-of-life parameters significantly improved following surgery. CONCLUSION: The robotic approach is feasible for performing targeted parathyroidectomy that avoids a neck scar. The clinical efficacy and cost-effectiveness of the robotic approach compared with conventional targeted parathyroidectomy warrant further evaluation to establish if this represents a viable alternative to the existing targeted techniques. PubMed-ID: 21546590 http://dx.doi.org/10.1177/0194599811402152

A Profile of Patients With Hyperparathyroidism Unde rgoing Lithium Therapy for Affective Psychiatric Disorders. Head Neck, 33(7):925-7. Kandil E, Dackiw AP, Alabbas H, Abdullah O, Tufaro AP, Tufano RP. 2011. BACKGROUND: Our objective was to evaluate whether lithium-induced hyperparathyroidism (LIHPT) is caused by single-gland versus multigland disease. METHODS: Medical records of 7 patients who underwent parathyroidectomy for LIHPT were reviewed. RESULTS: The mean preoperative calcium was 11.1 +/- 0.7 mg/dL. Six of 7 patients were rendered eucalcemic with surgery. Of the 6 patients successfully treated with surgery, 4 had single-gland disease, 1 had double adenomas, and 1 had 4-gland hyperplasia. Intraoperative intact serum parathyroid hormone (iPTH) accurately predicted resolution of hyperparathyroidism in 6 of 7 patients. One patient then subsequently developed persistent hyperparathyroidism refractory to further surgery. Localization studies defined the extent of disease in 5 of 7 patients. CONCLUSION: LIHPT presents with a spectrum of disease ranging from single-gland to multigland disease. The utility of preoperative localization studies and intraoperative iPTH in this population is uncertain. Bilateral exploration may be best to achieve a resolution of LIHPT. PubMed-ID: 21557377 http://dx.doi.org/10.1002/hed.21563

Parathyroidectomy in the Elderly: Analysis of 7313 Patients. J Surg Res, 170(2):240-6. Thomas DC, Roman SA, Sosa JA. 2011. BACKGROUND: The elderly are the fastest growing subset of the U.S. population, and suffer most from primary hyperparathyroidism. This is the first multi-institutional study to characterize 30-d outcomes in elderly patients undergoing parathyroidectomy. MATERIALS AND METHODS: Patients who underwent parathyroidectomy for primary hyperparathyroidism in ACS-NSQIP, 2005-8, were stratified into age groups: 45-64, 65-79, and >/=80 y. Independent patient variables included gender, race, inpatient/outpatient type, anesthesia, ASA classification, functional status, and presence/absence of >30 conditions. Outcomes included overall/system-specific complications, return to the OR, operating times, LOS, 30-d mortality. Patients 65-79 and >/=80 y were compared with younger ones using multivariable linear and logistic regression. RESULTS: A total of 7313 patients were identified: 77.8% women, 77.2% White, and 95.6% underwent first-time parathyroidectomy. Patients 65-79 and >/= 80y were more likely to have inpatient parathyroidectomies compared with younger patients (42.4%, 46.8% versus 36.0%) and higher ASA classification (42.4%, 59.8% versus 24.2%, all P < 0.01). Patients >/= 80 y were less likely than those 45-64 y to receive general anesthesia (84.9% versus 89.8%, P < 0.01). Patients >/= 65 y were more likely to have >/=1 complication (2.2% versus 1.3%, P < 0.01) and respiratory-specific complications compared with younger patients (0.9% versus 0.3%, P < 0.01). Patients 65-79 and >/=80 y were more likely to have extended hospital stays (7.7%, 12.2% versus 6.5%, P < 0.01); mortality rate for patients >/= 80 y was higher (0.8% versus <0.1%, P < 0.01). On multivariable analysis, patients >/= 65 y had increased risks for overall/respiratory complications and extended hospital stays, (all P < 0.01). CONCLUSIONS: Elderly patients sustain more morbidity following parathyroidectomy. Advanced age may be an independent risk factor worth considering in surgical decision-making. PubMed-ID: 21571309 http://dx.doi.org/10.1016/j.jss.2011.03.014


Mild Primary Hyperparathyroidism: Vitamin D Deficie ncy and Cardiovascular Risk Markers. J Clin Endocrinol Metab, 96(7):2112-8. Farahnak P, Larfars G, Sten-Linder M, Nilsson IL. 2011. CONTEXT: The extent and clinical significance of cardiovascular (CV) abnormalities associated with mild primary hyperparathyroidism (PHPT) are still matters for discussion. OBJECTIVE: The main objective of the present study was to evaluate biochemical CV risk markers in PHPT patients before and after parathyroidectomy (PTX) in comparison with controls. DESIGN AND SUBJECTS: In a prospective case-control design, 49 patients with PHPT and 49 healthy matched controls were included. METHODS: Blood pressure (BP), 25-OH-D, plasminogen activator inhibitor-1 activity, von Willebrand factor antigen, homocysteine, high-sensitivity C-reactive protein, IGF-I, and lipid profile were evaluated at baseline and 15 +/- 4 months after PTX. RESULTS: At baseline, the level of 25-OH-D was significantly lower in patients compared with controls (40.1 +/- 16.5 vs. 64.6 +/- 20.8 nmol/liter, P < 0.001) and increased after PTX (58.9 +/- 19.5, P < 0.001). Postoperatively, 25-OH-D was inversely correlated to the PTH level (r = -0.34; P < 0.05). Systolic BP (127.2 +/- 17.4 vs. 119.3 +/- 12.5 mm Hg, P < 0.05) and triglyceride (TG; 1.04 +/- 0.60 vs. 0.86 +/- 0.43 mmol/liter, P < 0.05) were higher in patients compared with controls and decreased slightly in patients after PTX (BP, 124.4 +/- 16.8 mm Hg, and TG, 0.94 +/- 0.50 mmol/liter, P < 0.05). Otherwise, there were no intergroup differences in coagulation, inflammatory, metabolic, and lipid status. CONCLUSIONS: Except for a lower 25-OH-D level and slightly higher systolic BP and TG levels, patients with mild PHPT without other CV risk factors did not differ from healthy controls as regards biomarkers predicting CV diseases. PTX had an overall positive effect on TG level, BP, and vitamin D status. PubMed-ID: 21593116 http://dx.doi.org/10.1210/jc.2011-0238

Absorption of Levothyroxine When Coadministered Wit h Various Calcium Formulations. Thyroid, 21(5):483-6. Zamfirescu I, Carlson HE. 2011. BACKGROUND: Calcium carbonate is a commonly used dietary supplement and has been shown to interfere with levothyroxine absorption. However, calcium citrate, which is also used for supplementation purposes, has not been studied previously and calcium acetate, which is used to treat hyperphosphatemia in renal failure, has been reported to show little or no interference with levothyroxine absorption in a retrospective pharmacoepidemiologic study. We aimed to compare the effect of these three calcium formulations on levothyroxine absorption. MATERIALS AND METHODS: The study was conducted in eight healthy, euthyroid adults. We performed single-dose pharmacokinetic studies in which we measured levothyroxine absorption when given alone or when coadministered with calcium carbonate, calcium citrate, or calcium acetate in doses containing 500 mg elemental calcium. Serum thyroxine was measured at intervals over a 6-hour period after ingestion of the study drugs. RESULTS: Coadministration of each of the three calcium preparations significantly reduced levothyroxine absorption by about 20%-25% compared with levothyroxine given alone. CONCLUSIONS: Contrary to a prior report, our data suggest that calcium acetate interferes with levothyroxine absorption in a manner similar to that seen with calcium carbonate and calcium citrate. Although the effect of calcium is modest compared with some other medications previously studied, hypothyroid patients should be cautioned to take their levothyroxine well-separated from all of these calcium formulations. PubMed-ID: 21595516 http://dx.doi.org/10.1089/thy.2010.0296

A COMPARATIVE STUDY OF PREOPERATIVE IMAGING METHODS IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM: US, MIBI, SPECT AND MRI. J Endocrinol Invest, Akbaba G, Berker D, Isik S, Aydin Y, Ciliz D, Peksoy I, Ozuguz U, Tutuncu YA, Guler S. 2011. Aim: This study compares the accuracy rates achieved in ultrasonography (US), 99mTcsestamibi (MIBI), single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) as imaging methods used in the preoperative localization of the enlarged parathyroid glands. Subjects and Methods: For the purposes of this study, US, MIBI, SPECT and MRI were performed on ninety-eight patients with primary hyperparathyroidism (pHPT). All patients underwent parathyroidectomy. Results: Preoperative localisation of an abnormal parathyroid gland was successfully performed in 82 of the cases scanned with US (83.7%), while the result was 66 in the cases scanned with MIBI (67.3%), 71 of the cases were successfully localised with SPECT (72.4%), while MRI revealed the diseased gland in only 60 of the total cases (61.2%). In MIBI positive and negative patients there was a statistically significant difference among cases in terms of adenoma volume (1.30+/-1.51 vs. 0.58+/-0.91, p < 0.05). Sensitivity, specificity and diagnostic accuracy values were 87.2%, 25.0%, and 83.0%; 70.2%, 50.0%, and 69.4%; 75.5%, 50.0%, and 74.5%; 63.8%, 50.0%, and 63.3% for US,


MIBI, SPECT and MRI, respectively. The respective values for sensitivity, specificity and diagnostic accuracy were 94.9%, 25.0% and 91.1% when US was combined with MIBI. Conclusions: Combining US and MIBI as imaging methods for preoperative imaging of pHPT often produces more satisfactory results. While the accuracy of US is relatively low in the ectopic localizations, the size of the lesion can be an important factor in the accuracy achieved with MIBI. PubMed-ID: 21623148 http://dx.doi.org/10.3275/7764

Fuller Albright and Our Current Understanding of Ca lcium and Phosphorus Regulation and Primary Hyperparathyroidism. Nefrologia, 31(3):346-57. Felsenfeld AJ, Levine BS, Kleeman CR. 2011. The major contributions of Fuller Albright to our understanding of calcium and phosphorus regulation and primary hyperparathyroidism are highlighted. Albright was the first investigator to initiate a systematic study of mineral metabolism. With resources limited to the measurement of serum calcium and phosphorus and the infusion of parathyroid extract, Albright used balance studies to establish a framework for our understanding of calcium and phosphorus regulation and primary hyperparathyroidism. Albright was the first to show that the etiology of primary hyperparathyroidism could be from either an adenoma or hyperplasia of the parathyroid glands and stone disease was a separate manifestation of primary hyperparathyroidism. Albright also showed that: 1) a renal threshold for calcium excretion was present in hypoparathyroid patients; 2) correction of hypocalcemia in hypoparathyroid patients with vitamin D had a phosphaturic action; 3) renal failure reduced the intestinal absorption of calcium in primary hyperparathyroidism; 4) the ''hungry bone'' syndrome developed after parathyroidectomy in severe primary hyperparathyroidism; and 5) a target organ can fail to respond to a hormone. He also suggested that a malignant tumor could be responsible for ectopic hormone production. Finally, our review integrates the observations of Albright with our current knowledge of calcium regulation and disorders. PubMed-ID: 21629339 http://dx.doi.org/10.3265/Nefrologia.pre2011.Mar.10774

Nephrolithiasis and Renal Calcifications in Primary Hyperparathyroidism. J Clin Endocrinol Metab, 96(8):2377-85. Rejnmark L, Vestergaard P, Mosekilde L. 2011. CONTEXT: Renal complications in terms of hypercalciuria, nephrolithiasis, and nephrocalcinosis are well-known risks in primary hyperparathyroidism (PHPT) and may lead to impaired renal function. EVIDENCE ACQUISITION: We reviewed published evidence on the occurrence, pathophysiology, and consequences of renal complications in PHPT and highlighted areas of uncertainty that should be investigated further. EVIDENCE SYNTHESIS: In asymptomatic PHPT, renal stones are present in approximately 7% of the patients, which is a significantly higher prevalence than among patients without PHPT (1.6%). Also, before diagnosis of PHPT, risk of hospital admissions due to renal stones is increased compared with the background population, and the risk remains increased for at least 10 yr after surgical cure from PHPT. However, shortly after parathyroidectomy, risk of recurrent stone episodes is reduced to the recurrence rate among patients with idiopathic renal stone disease. In general, patients with PHPT who develop nephrolithiasis are of younger age and more often are males, compared with those who do not form renal calcifications. Although 24-h urinary calcium is decreased after parathyroidectomy, studies have shown a higher renal calcium excretion and lower serum phosphate levels in former PHPT patients compared with healthy controls, suggesting that these patients have some additional mineral disorder. CONCLUSION: All patients with a diagnosis of PHPT should initially be evaluated for renal calcifications by unenhanced helical computed tomography. If calcifications are present, parathyroidectomy is recommended. If symptoms develop after parathyroidectomy, patients should be evaluated and treated similar to other patients with renal stones. PubMed-ID: 21646371 http://dx.doi.org/10.1210/jc.2011-0569

Minimally Invasive Parathyroid Surgery, the Norman 20% Rule: Is It Valid? Am Surg, 77(4):484-7. Quillo AR, Bumpous JM, Goldstein RE, Fleming MM, Flynn MB. 2011. The 20 per cent rule proposed by Norman established a guideline using radioactivity in the minimally invasive radioguided parathyroidectomy (MIRP) technique to localize and confirm removal of an abnormal parathyroid gland in patients with primary hyperparathyroidism. If radioactivity in the resected gland was at least 20 per cent of excision site/background radioactivity, the 20 per cent rule was satisfied. Patients meeting these criteria


underwent unilateral MIRP without intraoperative parathyroid hormone assay or intraoperative frozen section. The study aim was to independently evaluate the 20 per cent rule in MIRP patients with primary hyperparathyroidism. Using the University of Louisville Parathyroid Database from January 1, 1999 to December 31, 2007, 216 MIRP patients with complete radioguided and postoperative management data were identified. The average percentage of ex vivo parathyroid gland radioactivity compared with excision site/background radioactivity was 107 per cent with a range from 14 to 388 per cent. For 99 per cent (196/198) radioactivity recorded from the excised gland was at least 20 per cent of radioactivity recorded from the excision site. Normocalcemia was documented in 98.5 per cent (195/198) at 12 month follow-up. Our data supports the 20 per cent rule in that in 99 per cent of MIRP patients the resected gland radioactivity was at least 20 per cent of excision site radioactivity allowing localization and confirmation of an overactive gland without intraoperative parathyroid hormone monitoring or tissue analysis. PubMed-ID: 21679561

Use of a Handheld, Semiconductor (Cadmium Zinc Tell uride)-Based Gamma Camera in Navigation Surgery for Primary Hyperparathyroidism. Am Surg, 77(6):690-3. Fujii T, Yamaguchi S, Yajima R, Tsutsumi S, Uchida N, Asao T, Oriuch N, Kuwano H. 2011. The recent development of gamma-ray probes makes it possible to perform radioguided surgery for primary hyperparathyroidism (PHPT). There have only been a few reports, however, regarding the use of a handheld gamma camera to detect parathyroid adenoma intraoperatively. The aim of this preliminary study was to assess the efficiency of a semiconductor gamma camera (eZ-SCOPE AN) in navigation surgery for PHPT. The eZ-SCOPE is designed to be used as a handheld, regional diagnostic imaging device. Eleven consecutive patients with documented primary hyperparathyroidism underwent surgery using this compact camera. Scintigraphy images of the neck by eZ-SCOPE were acquired: 1) before skin incision; 2) after adenoma location; 3) after adenoma excision; and 4) ex vivo imaging of the specimen. In scan-positive cases by preoperative Tc-MIBI, the eZ-SCOPE revealed parathyroid adenoma in all cases (100%), whereas ultrasound and CT showed a single adenoma in 63.6 and 72.7 per cent of cases, respectively. Navigation surgery for PHPT using the eZ-SCOPE permitted intraoperative identification and removal of parathyroid adenoma in all cases. Scintigraphy images of the neck by eZ-SCOPE also revealed a single adenoma even before skin incision. Our results suggest that Tc-MIBI scintigraphy with the eZ-SCOPE is useful for navigation surgery for PHPT. The eZ-SCOPE is useful for skin marking and could be easily applied for minimally invasive radioguided parathyroidectomy in scan-positive cases. PubMed-ID: 21679634

Effect of Incomplete Parathyroidectomy Preserving E ntire Parathyroid Glands on Renal Graft Function. Arch Surg, 146(6):704-10. Jager MD, Kaaden S, Emmanouilidis N, Luck R, Beckmann JH, Guner Z, Kespohl H, Glockzin K, Aselmann H, Kaudel CP, Schwarz A, Zapf A, Klempnauer J, Scheumann GF. 2011. HYPOTHESIS: Parathyroidectomy (PT) corrects tertiary hyperparathyroidism in patients who have received renal grafts but can result in deterioration of renal function. OBJECTIVE: To compare different surgical procedures for their effect on renal function and efficacy to cure tertiary hyperparathyroidism. DESIGN: A retrospective cohort study. SETTING: University clinic. PATIENTS: Eighty-three patients with functioning renal grafts receiving PT for the first time. INTERVENTIONS: Group 1 received an incomplete PT, with at least 1 entire parathyroid gland (PG) remaining in situ (n = 12). Group 2 received an incomplete PT, with the most morphologically conserved PG partially resected (n = 22). Group 3 received a complete PT, with autotransplantation of PG tissue (n = 49). MAIN OUTCOMES MEASURES: The primary end point was the postoperative change in glomerular filtration rate. Secondary end points were rates of redialysis, hypercalcemia, and hyperparathyroidism within 5 years. RESULTS: A decrease in glomerular filtration rate occurred postoperatively in 75 patients (90%) and correlated significantly with the extent of PG resection. Recovery of renal function at month 6 was observed in group 1, but not in groups 2 and 3 (P < .001). Seven patients (8%) needed permanent dialysis (1 in group 2 and 6 in group 3). Hypercalcemia was abrogated in 78 patients (94%), without significant differences among the groups. Assessment of parathyroid hormone levels in accordance with target ranges from the Kidney Disease Outcomes Quality Initiative guidelines did not reveal significant differences in the rates of recurrent hyperparathyroidism. CONCLUSION: Incomplete PT preserving at least 1 entire PG does not cause deterioration of renal graft function and provides long-term correction of hypercalcemia and tertiary hyperparathyroidism. PubMed-ID: 21690447 http://dx.doi.org/10.1001/archsurg.2011.138


Teriparatide Efficacy in the Treatment of Severe Hy pocalcemia After Kidney Transplantation in Parathyroidectomized Patients: a Series of Five Cas e Reports. Transplantation, 92(3):316-20. Nogueira EL, Costa AC, Santana A, Guerra JO, Silva S, Mil-Homens C, Costa AG. 2011. BACKGROUND: Teriparatide is a recombinant human parathormone (PTH 1-34) currently approved for the treatment of osteoporosis with high risk of fracture. In this study, we analyze the efficacy and safety profile of teriparatide therapy in severe and prolonged hypocalcemia after kidney transplantation in patients previously submitted to parathyroidectomy. METHODS: The authors report results from a series of five hemodialyzed patients (mean age: 50+/-15 years; three female) previously submitted to parathyroidectomy to control secondary hyperparathyroidism. All patients had developed severe refractory hypocalcemia (calcium minimum levels: 5+/-1.4 mg/dL) early after kidney transplantation. The effect of teriparatide in calcemia and phosphatemia levels was analyzed, and variations in calcium and vitamin D analog requirements were analyzed. Secondary effects and serum creatinine changes were also ascertained. RESULTS: Teriparatide therapy was initiated 32+/-14 days after the development of hypocalcemia. As a result, calcemia levels increased (median+/-standard deviation [SD]: 6.7+/-0.8 vs. 8.5+/-0.8 mg/dL, P=0.024) allowing suspension of intravenous calcium in two patients and reduction of calcitriol doses (mean+/-SD: 1.1+/-0.38 vs. 0.55+/-0.27 mug/day, P=0.004). In addition, phosphatemia levels (median+/-SD: 5.1+/-1.5 vs. 3.9+/-0.5 mg/dL, P=0.09) and calcium carbonate requirements (mean+/-SD: 13.8+/-9.4 vs. 7.2 +/-3.7 g/day, P=0.9) exhibited declining trends. No secondary effects were observed and creatinemia remained stable. CONCLUSIONS: Our data strongly suggest that refractory hypocalcemia after kidney transplantation in patients with low PTH levels can be successfully treated with teriparatide. PTH analog therapy leads to faster normalization of calcemia, permits earlier suspension of intravenous calcium supplementation, and reduces calcitriol requirements. PubMed-ID: 21694663 http://dx.doi.org/10.1097/TP.0b013e3182247b98

The Necessity and Reliability of Intraoperative Par athyroid Hormone (PTH) Testing in Patients With Mil d Hyperparathyroidism and PTH Levels in the Normal Ra nge. World J Surg, 35(9):2006-9. Alhefdhi A, Pinchot SN, Davis R, Sippel RS, Chen H. 2011. BACKGROUND: Intraoperative parathyroid hormone (IoPTH) testing is useful in the management of hyperparathyroidism. The successful removal of hypersecreting parathyroids is indicated by a decrease in PTH levels >50% within 15 min. A subset of patients with mild hyperparathyroidism will actually have starting PTH levels in the normal range. We sought to determine if IoPTH testing is necessary in these patients and if the 50% rule delineating surgical cure is reliable. METHODS: A retrospective review was performed on all patients who underwent parathyroidectomy for hyperparathyroidism at a single institution from 3/2001 to 8/2008. RESULTS: Of the 1,001 patients, 142 (14%) had mild hyperparathyroidism and normal baseline PTH levels (<65 pg/ml). Their mean PTH was 59 +/- 1 pg/ml. During surgery, 105 (74%) had a >50% decline in PTH levels after resection of hyperfunctioning parathyroid glands, and their operations were terminated. In contrast, 37 (26%) patients did not have a >50% decline in PTH levels leading to further surgical exploration. In these 37 patients, the PTH levels fell by >50% after the removal of the additional glands in 25 patients (17.6%) and dropped after 20 min in 7 patients (4.9%). In 5 patients (3.5%) the IoPTH did not drop. Of the 142 total patients, 91 had single adenomas and 51 patients had multi-gland disease. All patients (100%) were cured (normal serum calcium after 6 months). CONCLUSIONS: Intraoperative PTH testing plays an important role in the operative management in 14% of patients with mild hyperparathyroidism. Importantly, a 50% decline in IoPTH level within 15 min of parathyroidectomy is 96.5% reliable in predicting cure in these patients with PTH starting in the normal range. PubMed-ID: 21713573 http://dx.doi.org/10.1007/s00268-011-1179-3

Use of Ultrasound to Assess the Response to Therapy for Secondary Hyperparathyroidism. Am J Kidney Dis, 58(3):485-91. Meola M, Petrucci I, Colombini E, Barsotti G. 2011. Secondary hyperparathyroidism (SHPT) is a common complication in patients with chronic kidney disease. In SHPT, the biology of parathyroid cells changes significantly toward diffuse nodular hyperplasia. Currently, diagnosis of SHPT is based on intact parathyroid hormone serum levels and parameters of mineral metabolism. The morphologic diagnosis of SHPT relies on high-resolution ultrasonography with color Doppler imaging. This report describes a maintenance hemodialysis patient with severe SHPT treated using conventional therapy (phosphate binders and oral/intravenous vitamin D or analogues) and the subsequent addition of a calcimimetic. The role of color Doppler ultrasonography in the diagnosis, clinical follow-up, and assessment of therapeutic response of SHPT is discussed. This case suggests that the availability of calcimimetics has changed the natural


history of clinical SHPT and may change the therapeutic utility of parathyroidectomy. Use of color Doppler ultrasonography further supports these therapeutic advances, allowing evaluation of the morphologic and vascular changes in hyperplastic parathyroid glands and aiding clinical, pharmacologic, and surgical strategies. PubMed-ID: 21715073 http://dx.doi.org/10.1053/j.ajkd.2011.03.030

Use of Percutaneous Ethanol Injection Therapy for R ecurrent Secondary Hyperparathyroidism After Subtotal Parathyroidectomy. Int J Nephrol, 2011:246734. Douthat WG, Cardozo G, Garay G, Orozco S, Chiurchiu C, de la FJ, de AJ, Massari PU. 2011. We evaluated the efficacy of percutaneous ethanol injection therapy (PEIT) as a therapeutic option for recurrence of secondary hyperparathyroidism after subtotal parathyroidectomy in ESRD patients. Six patients underwent PEIT. A mean of 1.3 +/- 0.8 ethanol injections was performed. Nodular volume was 1.5 +/- 1.7 cm(3), and 2.8 +/- 2.8 cm(3) of ethanol was injected per patient. After ethanol injection PTH decreased significantly (1897 +/- 754 to 549 +/- 863 pg/mL (P < .01)). There was also a reduction in serum calcium, phosphorus and calcium-phosphorus product. A positive and significant correlation was found between nodular volume with ethanol injected and time from parathyroidectomy. Only one patient required hospitalization due to severe hypocalcaemia. In other two cases, local discomfort and temporary mild dysphonia were registered. PEIT is an effective treatment to control recurrences of secondary hyperparathyroidism postsubtotal parathyroidectomy. PubMed-ID: 21716690 http://dx.doi.org/10.4061/2011/246734

Can Biochemical Abnormalities Predict Symptomatolog y in Patients With Primary Hyperparathyroidism? J Am Coll Surg, 213(3):410-4. Bargren AE, Repplinger D, Chen H, Sippel RS. 2011. BACKGROUND: Primary hyperparathyroidism presents with a myriad of symptoms, which range in severity. The cause of these symptoms is not well understood. We sought to determine if the severity of preoperative biochemical abnormalities (calcium, parathyroid hormone, vitamin D levels) correlated with symptomatology in patients undergoing surgical treatment for primary hyperparathyroidism. STUDY DESIGN: Over 15 months, 229 consecutive patients with primary hyperparathyroidism completed a symptom questionnaire before parathyroidectomy. The symptom profiles of patients with significant hypercalcemia at initial presentation (>/=11.2 mg/dL) and those with baseline calcium levels (<11.2 mg/dL) were compared. The patients were also categorized based on parathyroid hormone (< or >/=130 pg/mL) and vitamin D (< or >/=30 ng/mL) and analyzed in a similar manner. RESULTS: Seventy-eight patients (34%) had a baseline calcium >/=11.2 mg/dL, but compared with patients with calcium <11.2 mg/dL, only the incidence of nephrolithiasis was more common in those patients with significant hypercalcemia (18% vs 9%, p = 0.04). Conversely, depression, bone or joint pain, and constipation were all significantly more common in patients with calcium <11.2mg/dL (p = 0.006, 0.001, and 0.031, respectively). Patients analyzed based on parathyroid hormone and vitamin D levels showed no significant difference in symptom presentation. CONCLUSIONS: These data indicate that the degree of parathyroid hormone elevation and the presence of vitamin D deficiency do not correlate with the presence of symptoms in patients with primary hyperparathyroidism. Significant hypercalcemia was associated with nephrolithiasis, but interestingly, patients with milder hypercalcemia had significantly more depression, bone or joint pain, and constipation, suggesting that these symptoms are likely not mediated by hypercalcemia. PubMed-ID: 21723154 http://dx.doi.org/10.1016/j.jamcollsurg.2011.06.401

Eucalcemic Parathyroid Hormone Elevation After Para thyroidectomy for Primary Sporadic Hyperparathyroidism: Risk Factors, Trend, and Outco me. Ann Surg Oncol, Lang BH, Wong IY, Wong KP, Lo CY. 2011. BACKGROUND: Patients with eucalcemic parathyroid hormone elevation (ePTH) after parathyroidectomy for primary hyperparathyroidism (HPT) may be at risk of recurrence. We aimed to examine risk factors, trend of PTH level, and outcome of patients with ePTH 6 months after parathyroidectomy. METHODS: A total of 161 primary HPT were analyzed. The 6-month postoperative calcium and PTH levels were obtained. ePTH was defined as an elevated PTH level in the presence of normocalcemia. At 6 months, 98 had eucalcemic normal PTH and 63 (39.1%) had ePTH. Perioperative variables, PTH trend, and outcome were compared between 2 groups. Multivariable analyses were performed to identify independent preoperative and operative/postoperative risk factors for ePTH. RESULTS: Among preoperative factors, advanced age (odds ratio [OR] = 1.042, P = .027) and low 25-hydroxyvitamin D(3) (25OHD(3)) (OR = 1.043, P = .009) were independently associated with ePTH,


whereas among operative/postoperative factors, high 10-min intraoperative PTH level (OR = 1.015, P = .040) and high postoperative 3-month PTH (OR = 1.048, P < .001) were independently associated with ePTH. After a mean follow-up of 38.7 months, recurrence rate was similar between the 2 groups (P = 1.00). In the first 2 postoperative years, 75 (46.6%) had ePTH on at least 1 occasion and 8 (5.0%) had persistently ePTH on every occasion. CONCLUSIONS: Advanced age, low 25OHD(3), high 10-min intraoperative PTH, and high postoperative 3-month PTH were independently associated with ePTH at 6-month. Although 39.1% of patients had ePTH at 6 months, more than 50% had at least 1 ePTH within the first 2 years of follow-up. Recurrence appeared similar between those with or without ePTH at 6 months. PubMed-ID: 21732144 http://dx.doi.org/10.1245/s10434-011-1846-5

Minimally Invasive Parathyroidectomy. Int J Endocrinol, 2011:206502. Starker LF, Fonseca AL, Carling T, Udelsman R. 2011. Minimally invasive parathyroidectomy (MIP) is an operative approach for the treatment of primary hyperparathyroidism (pHPT). Currently, routine use of improved preoperative localization studies, cervical block anesthesia in the conscious patient, and intraoperative parathyroid hormone analyses aid in guiding surgical therapy. MIP requires less surgical dissection causing decreased trauma to tissues, can be performed safely in the ambulatory setting, and is at least as effective as standard cervical exploration. This paper reviews advances in preoperative localization, anesthetic techniques, and intraoperative management of patients undergoing MIP for the treatment of pHPT. PubMed-ID: 21747851 http://dx.doi.org/10.1155/2011/206502

Outcomes Analysis of Intraoperative Adjuncts During Minimally Invasive Parathyroidectomy for Primary Hyperparathyroidism. Am J Surg, Nagar S, Reid D, Czako P, Long G, Shanley C. 2011. BACKGROUND: The aim of this study was to determine whether minimally invasive radioguided parathyroidectomy (MIRP) and intraoperative parathyroid hormone-guided parathyroidectomy (ioPTH) have equivalent intermediate-term outcomes in primary hyperparathyroidism (PHPT). METHODS: A retrospective study of 244 patients who underwent parathyroidectomy for PHPT in a 25-month time period was conducted. Patients who either underwent. PubMed-ID: 21752350 http://dx.doi.org/10.1016/j.amjsurg.2010.10.015

Minimally Invasive Parathyroidectomy: a Community H ospital Experience. Arch Surg, 146(7):876-8. Vaid S, Pandelidis S. 2011. Minimally invasive parathyroidectomy (MIP) for primary hyperparathyroidism can be successfully performed using preoperative sestamibi scan and intraoperative radioguidance without the need of measurement of intraoperative parathyroid hormone (PTH) levels. The purpose of our study was to review the outcomes of MIPs performed in a community hospital without measuring PTH levels intraoperatively and to demonstrate that this is an effective therapeutic modality with comparable success rates. We performed a retrospective medical record review of patients undergoing MIPs from April 1, 1998, through May 31, 2005, in a 500-bed community hospital. A total of 188 parathyroidectomies for primary hyperparathyroidism were performed by a single surgeon during the study period, 111 of which were MIPs. In this series of 111 patients, we found 2 recurrences, achieving a success rate of 98.2%. Higher preoperative PTH levels and gland weight had a direct correlation with the successful performance of MIP. PubMed-ID: 21768437 http://dx.doi.org/10.1001/archsurg.2011.155

Surgical Treatment of Tertiary Hyperparathyroidism After Renal Transplantation: A 31-Year Experience in a Single Institution. Endocr J, Park JH, Kang SW, Jeong JJ, Nam KH, Chang HS, Chung WY, Park CS. 2011. Tertiary hyperparathyroidism (tHPT) most commonly refers to a persistent secondary hyperparathyroidism even after successful renal transplantation. Parathyroidectomy (PTX) is an efficient method for treatment of tHPT. In this study, we examined our 31-year experience with patients who underwent PTX for tHPT after KTX and


assessed the effects of PTX on graft function according to the type of surgery. Among 2,981 recipients who underwent renal allograft between April 1979 and Dec. 2010, 15 patients (0.5%) were identified as having tHPT and underwent PTX. Levels of intact parathyroid hormone (iPTH) and serum calcium were measured before and after PTX for evaluation of the therapeutic effect, and glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) equation for investigation of any effect on graft function. One patient showed persistent hyperparathyroidism and hypercalcemia after limited PTX. We experienced 14 successful PTXs, including 3 total PTX with autotransplantations, 8 subtotal PTXs, and 3 limited PTXs. Level of iPTH and serum calcium were at normal range after PTX. Estimated GFR decreased after PTX. Total PTX with autotransplantation showed a tendency of more decrease in the values of iPTH, and GFR after PTX than Subtotal PTX. PTX can cure tHPT-specific symptoms and signs by recovery of hypercalcemia, but may carry the risk of deterioration of kidney graft function. We suspect that subtotal PTX, rather than total PTX with AT, prevent any risk of kidney graft deterioration in surgical treatment of tHPT, and, in selective tHPT patients, limited PTX might be recommended. PubMed-ID: 21804261

Sometimes Less Is More. Arch Surg, 146(6):710. Chen H, Sippel RS. 2011. PubMed-ID: 21830339

Transoral Thyroid and Parathyroid Surgery--Developm ent of a New Transoral Technique. Surgery, 150(1):108-15. Karakas E, Steinfeldt T, Gockel A, Schlosshauer T, Dietz C, Jager J, Westermann R, Sommer F, Richard HR, Exner C, Sesterhenn AM, Bartsch DK. 2011. BACKGROUND: Transluminal interventions via so-called natural orifices are gaining interest because they allow operative treatment without any skin incision. We previously described a transoral access for (para-)thyroid resection in pigs. To proceed with the first clinical trials, we evaluated the safety of the new technique. METHODS: Transoral hemithyroidectomies were performed on 10 living pigs using a special cervicoscope and conventional laparoscopic instruments. Follow-up examinations were carried out for 14 days and followed by autopsy, which included macroscopic evaluation, microbiologic investigations, and blood testing. In addition, refinement of the new technique was achieved by developing the techniques in 10 human cadavers. Finally, transoral parathyroidectomies were performed in 2 patients with primary hyperparathyroidism and a preoperatively localized parathyroid adenoma. RESULTS: All animal transoral hemithyroidectomies were performed without complications. Postoperatively, oral intake, weight gain, and white blood cell count remained normal. At autopsy, the access route, and operative field showed no signs of infection, and microbiologic swabs remained sterile. Based on these results, a transoral parathyroidectomy was performed successfully in 2 female patients with primary hyperparathyroidism; 1 patient experienced a transient palsy of the right hypoglossal nerve. CONCLUSION: Transoral parathyroid and thyroid operation is feasible; however, additional controlled clinical studies are required to evaluate the safety and success rates of this new technique. PubMed-ID: 21458014 http://dx.doi.org/10.1016/j.surg.2010.12.016

Thyroidectomy and Parathyroidectomy in Patients Wit h High Body Mass Index Are Safe Overall: Analysis of 26,864 Patients. Surgery, Buerba R, Roman SA, Sosa JA. 2011. BACKGROUND: Obesity is a national epidemic. Prior studies of the impact of body mass index (BMI) on surgical outcomes from cervical endocrine procedures have come from high-volume, single institutions. Our study characterizes the 30-day clinical and economic outcomes in patients with high BMI from a multi-institutional database. METHODS: Patients undergoing thyroidectomy or parathyroidectomy in the American College of Surgeons National Surgery Quality Improvement Program, 2005-2008 were categorized into 4 groups BMI based on: normal, overweight, obese, and morbidly obese. Overweight, obese, and morbidly obese patients were compared with patients with normal BMI using a chi(2) test and an analysis of variance. Multivariable linear/logistic regression models were used to adjust for preoperative risk factors. RESULTS: In all, 18,825 patients underwent thyroidectomy. Overweight, obese, and morbidly obese patients were more likely to have total thyroidectomy, substernal thyroids, general anesthesia, operations of greater duration, and an overall or wound complication (all P < .01). On a multivariable analysis, morbidly obese patients had an increased risk for urinary complications (P < .05); obese and morbidly obese patients had an increased risk for overall or wound complications (P < .01); overweight, obese, and morbidly obese patients had operations of greater duration (P <


.05). In all, 8,039 patients underwent parathyroidectomy. Overweight, obese, and morbidly obese patients were more likely to have general anesthesia and operations of greater duration (all P < .01). On multivariable analysis, morbidly obese patients had operations of greater duration (P < .05) and more wound complications (P = .05). CONCLUSION: Patients with high BMI seem to require operations of greater duration and sustain more morbidity after cervical endocrine procedures than patients with normal BMI, but these differences may not be clinically significant. Thyroidectomy and parathyroidectomy can be performed safely, with appropriate surgical decision making. PubMed-ID: 21621238 http://dx.doi.org/10.1016/j.surg.2011.02.017


Adrenals

Meta-Analyses Malignant Pheochromocytoma: a Review. Am J Surg, 201(5):700-8. Harari A, Inabnet WB, III. 2011. BACKGROUND: Pheochromocytomas are rare catecholamine-secreting tumors. Approximately 10 percent of pheochromocytomas are malignant. Traditionally, there has been no reliable method available to predict the malignant potential of pheochromocytoma. However, recent research has increased focus on differentiating at the time of surgery/diagnosis those pheochromocytoma tumors which have malignant potential. In this review, we discuss the current information known of malignant pheochromocytomas. DATA SOURCES: The PubMed database was searched for articles on malignant pheochromocytoma published between 1993 and 2010. CONCLUSIONS: The difficult task of predicting the malignant potential of a pheochromocytoma has yet to be answered definitively. However, all the studies presented give an idea of what we may look for in these tumors at the time of diagnosis. We have provided an algorithm based on the most current information known. A much larger study should be performed to test many of these theories with enough power to determine a standard of care. PubMed-ID: 20870212 http://dx.doi.org/10.1016/j.amjsurg.2010.04.012

Clinical Review: Diagnosis and Treatment of Subclin ical Hypercortisolism. J Clin Endocrinol Metab, 96(5):1223-36. Chiodini I. 2011. CONTEXT: Subclinical hypercortisolism (SH) is a condition of biochemical cortisol excess without the classical signs or symptoms of overt hypercortisolism. It is thought to be present in the 5-30% of patients with incidentally discovered adrenal mass (adrenal incidentalomas), which in turn are found in 4-7% of the adult population. Therefore, SH has been suggested to be present in 0.2-2.0% of the adult population. Some studies suggested that this condition is present in 1-10% of patients with diabetes or established osteoporosis. The present manuscript reviews the literature on diagnostic procedures and the metabolic effect of the recovery from SH. EVIDENCE ACQUISITION: A PubMed search was used to identify the available studies. The most relevant studies from 1992 to November 2010 have been included in the review. EVIDENCE SYNTHESIS: The available data suggest that SH may be associated with chronic complications, such as hypertension, diabetes mellitus, overweight/obesity, and osteoporosis. The available intervention studies suggest that the recovery from SH may lead to the improvement of hypertension and diabetes mellitus. A retrospective study suggests that this beneficial effect could be predicted before surgery. CONCLUSIONS: SH is suggested to be associated with some chronic complications of overt cortisol excess. Recovery from this condition seems to improve these complications. However, a large, prospective, randomized study is needed to confirm this hypothesis and to establish the best diagnostic approach to identify patients with adrenal incidentalomas who can benefit from surgery. PubMed-ID: 21367932 http://dx.doi.org/10.1210/jc.2010-2722


Other Articles Outpatient Laparoscopic Adrenalectomy: a New Step A head. Surg Endosc, 25(8):2570-3. Ramirez-Plaza CP, Perales JL, Camero NM, Rodriguez-Canete A, Bondia-Navarro JA, Santoyo-Santoyo J. 2011. BACKGROUND: The feasibility of performing laparoscopic adrenalectomy (LA) as an outpatient procedure in selected patients in the context of a specialized unit has been assessed in this study. METHODS: Retrospective cohort of 22 patients who underwent LA without hospital admission under strict selection criteria within a specific laparoscopic surgery unit of a tertiary hospital center has been reported. Patient demographics, indications for surgery, operative data, outpatient management, morbidity, and immediate follow-up have been analyzed.


RESULTS: The mean age of the patients was 50.9 years (median 52.5, range 28-65) and 13 (59.1%) were women. All patients underwent successful LA and none of them required conversion to laparotomy. The mean length of the procedure was 56.6 min (median 60, range 15-120 min) and no patient required transfusion. The most common indications for surgery were adrenal incidentaloma and primary hyperaldosteronism (36.4% each). Three patients accurately complied with the MAS regimen and the other 19 spent the night on a DC basis and were discharged with the hospital stay being less than 23 h. No patient required readmission and relevant events occurred only in three patients. With regard to postoperative pain management, only six patients (27.27%) required more than 1 week of analgesics. In 68.1% of the cases, resuming physical and professional activity took less than 2 weeks and only three patients required more than 1 month before restoring a "normal life." CONCLUSION: By applying strict protocol and selection criteria, LA can be safely and successfully performed as an outpatient procedure within an experienced laparoscopic unit. PubMed-ID: 21359891 http://dx.doi.org/10.1007/s00464-011-1588-2

Adrenocortical Carcinoma: a Clinician's Update. Nat Rev Endocrinol, 7(6):323-35. Fassnacht M, Libe R, Kroiss M, Allolio B. 2011. Adrenocortical carcinoma is a rare heterogeneous neoplasm with an incompletely understood pathogenesis and a poor prognosis. Previous studies have identified overexpression of insulin-like growth factor 2 (IGF-2) and constitutive activation of beta-catenin as key factors involved in the development of adrenocortical carcinoma. Most patients present with steroid hormone excess, for example Cushing syndrome or virilization, or abdominal mass effects, but a growing proportion of patients with adrenocortical carcinoma (currently >15%) is initially diagnosed incidentally. No general consensus on the diagnostic and therapeutic measures for adrenocortical carcinoma exists, but collaborative efforts, such as international conferences and networks, including the European Network for the Study of Adrenal Tumors (ENSAT), have substantially advanced the field. In patients with suspected adrenocortical carcinoma, a thorough endocrine and imaging work-up is recommended to guide the surgical approach aimed at complete resection of the tumor. To establish an adequate basis for treatment decisions, pathology reports include the Weiss score to assess malignancy, the resection status and the Ki67 index. As recurrence is frequent, close follow-up initially every 3 months is mandatory. Most patients benefit from adjuvant mitotane treatment. In metastatic disease, mitotane is the cornerstone of initial treatment, and cytotoxic drugs should be added in case of progression. Results of a large phase III trial in advanced adrenocortical carcinoma are anticipated for 2011 and will hopefully establish a benchmark therapy. New targeted therapies, for example, IGF-1 receptor inhibitors, are under investigation and may soon improve current treatment options. PubMed-ID: 21386792 http://dx.doi.org/10.1038/nrendo.2010.235

Obesity Is a Predictor of Morbidity in 1,629 Patien ts Who Underwent Adrenalectomy. World J Surg, 35(6):1287-95. Kazaure HS, Roman SA, Sosa JA. 2011. BACKGROUND: We examined the impact of obesity on 30-day outcomes of adrenalectomy using a multi-institutional database. METHODS: Patients who underwent adrenalectomy in 2005-2008 according to the American College of Surgeons-National Surgical Quality Improvement Project (ACS-NSQIP) data set were grouped by body mass index (BMI): normal weight (BMI=18.5-24.9 kg/m2), overweight (BMI=25.0-29.9 kg/m2), obese (BMI=30.0-34.9 kg/m2), and morbidly obese (BMI>/=35 kg/m2). Outcomes of the higher BMI groups were compared to those of the normal BMI group using chi2, analysis of variance (ANOVA), and multivariate regression. RESULTS: There were 1,629 patients in the study: 22% were normal weight, 31% overweight, 22.2% obese, and 24.7% morbidly obese. Compared to normal-weight patients, obese and morbidly obese patients had a 12.5 and 16.7% increase in operation times (129 vs. 145 and 150 min, respectively, p</=0.01) and sustained more wound complications (0.2 vs. 0.4 and 1.2%, p<0.001), including superficial and deep wound infections (p<0.001 and p<0.01, respectively). Morbid obesity independently predicted overall complications (odds ratio [OR] 2.9, 95% confidence interval [CI]: 1.7-5.7), wound complications (OR 6.1, 95% CI: 2.0-18.9), and septic complications (OR 3.1, 95% CI: 1.1-8.8). Obesity independently predicted longer total time in the operating room (p<0.006). There were no differences in rates of reoperation and length of hospital stay by BMI category. CONCLUSION: Obesity is an independent risk factor that needs to be considered in surgical decisions regarding adrenalectomy. Morbidly obese adrenalectomy patients are particularly at risk for wound and septic complications. PubMed-ID: 21455782 http://dx.doi.org/10.1007/s00268-011-1070-2


Adrenal Venous Sampling Is Crucial Before an Adrena lectomy Whatever the Adrenal-Nodule Size on Computed Tomography. J Hypertens, 29(6):1196-202. Sarlon-Bartoli G, Michel N, Taieb D, Mancini J, Gonthier C, Silhol F, Muller C, Bartoli JM, Sebag F, Henry JF, Deharo JC, Vaisse B. 2011. OBJECTIVE: To assess the additional value of adrenal venous sampling (AVS) to diagnose primary aldosteronism sub-types in patients who have a unilateral nodule detected by computed tomography (CT scan) and who should undergo an adrenalectomy. METHODS: A retrospective study to assess consecutive patients with primary aldosteronism undergoing an adrenal CT scan and AVS. Criterion for selective cannulation was an equal or higher cortisol level in the adrenal vein compared to the inferior vena cava. An adrenal-vein aldosterone-to-cortisol ratio of at least two times higher than the other side defined lateralization of aldosterone production. RESULTS: Sixty-seven patients (mean age 52 years, 39 men) underwent a CT scan and AVS. In nine patients (13%), cannulation of the right adrenal vein led to a technical failure. Both procedures led to diagnosis of 29 patients with adenoma-producing aldosterone (APA; 50%), 23 bilateral adrenal hyperplasias (40%), and six unilateral adrenal hyperplasias (10%). Of the 45 patients with a nodule detected by CT, subsequent AVS showed bilateral secretion in 16 patients (36%). Compared to the strategy of coupling CT scans with AVS to diagnosis APA, a CT scan alone had an accuracy of 72.4% (P < 0.001). Among patients with a macronodule detected by CT, 13 (37%) had bilateral secretion as assessed by AVS. The patients with a macronodule detected by CT alone had the same risk of a discrepancy as those with a small nodule (P = 0.99). CONCLUSION: AVS is essential to diagnose the unilateral hypersecretion of aldosterone, even in patients in whom a unilateral macronodule is detected by CT, to avoid unnecessary surgery. PubMed-ID: 21478754 http://dx.doi.org/10.1097/HJH.0b013e32834666af

Primary Aldosteronism: Results of Adrenalectomy for Nonsingle Adenoma. J Am Coll Surg, 213(1):106-12. Quillo AR, Grant CS, Thompson GB, Farley DR, Richards ML, Young WF. 2011. BACKGROUND: Historically, treatment of confirmed primary aldosteronism has been adrenalectomy for unilateral adenoma; bilateral hypersecretion is treated medically. Increasingly, we use adrenal venous sampling (AVS) to define unilateral hypersecretion. Histology of glands resected based on AVS often reveals multiple nodules or hyperplasia. The aim of this study was to compare patients with multiple nodules or hyperplasia with those with single adenoma with regard to cure, preoperative imaging, AVS ratio, and biochemical evaluation to determine if a nonsingle adenoma (NSA) process could be predicted to impact extent of adrenalectomy. STUDY DESIGN: This was a retrospective study reviewing a single-institutional surgical experience at a tertiary academic center from 1993 to 2008, during which 215 patients with primary aldosteronism underwent unilateral adrenalectomy based on imaging of a single adenoma (normal contralateral gland) or AVS ratios. Histology included single adenoma versus NSA; cure was defined as normal immediate postoperative plasma or urine aldosterone level, normal aldosterone:renin ratio, or normotension without antihypertensive medications. RESULTS: Follow-up (mean 13 months, range 0 to 185 months) was available for 167 patients: 132 (79%) single adenoma and 35 (21%) NSA. All 35 patients with NSA and 128 patients (97%) with single adenoma were cured. Imaging studies correctly predicted NSA in 29% and 57% when combined with AVS. Identifying patients with NSA preoperatively was impossible biochemically: mean serum and urinary aldosterone levels and AVS ratios were not different than those of the single adenoma group. CONCLUSIONS: Twenty-one percent of patients had NSA, all cured by unilateral adrenalectomy. No preoperative evaluation reliably predicted NSA. Therefore, total unilateral adrenalectomy was safest given the potential for incomplete resection with partial adrenalectomy. Accurate AVS is highly predictive of cure irrespective of the unilateral adrenal histology. PubMed-ID: 21489832 http://dx.doi.org/10.1016/j.jamcollsurg.2011.03.007

A Comprehensive Review of the Clinical Aspects of P rimary Aldosteronism. Nat Rev Endocrinol, 7(8):485-95. Rossi GP. 2011. Primary aldosteronism is much more common than previously thought. The high prevalence of primary aldosteronism, the damage this condition does to the heart, blood vessels and kidneys (which causes a high rate of cardiovascular events), along with the notion that a timely diagnosis followed by an appropriate therapy can correct the arterial hypertension and hypokalemia, justify efforts to search for primary aldosteronism in many patients with hypertension. Most centers can use a cost-effective strategy to screen for patients with primary aldosteronism. By contrast, the identification of primary aldosteronism subtypes, which involves adrenal-vein sampling, should only be undertaken at tertiary referral centers that have experience in performing and


interpreting this test. The identification of a curable form of primary aldosteronism can be beneficial for the patient. In some subgroups of patients with hypertension who are at high risk of primary aldosteronism or can benefit most from an accurate diagnosis, an aggressive diagnostic approach is necessary. PubMed-ID: 21610687 http://dx.doi.org/10.1038/nrendo.2011.76

Medical and Surgical Evaluation and Treatment of Ad renal Incidentalomas. J Clin Endocrinol Metab, 96(7):2004-15. Zeiger MA, Siegelman SS, Hamrahian AH. 2011. INTRODUCTION: Adrenal incidentalomas are detected in approximately 4% of patients undergoing high-resolution abdominal imaging studies. The majority of adrenal incidentalomas are benign, but careful evaluation of all patients is warranted to be certain that primary adrenocortical carcinoma and functional adenomas are not missed. METHODS: The diagnostic approach in patients with adrenal incidentalomas should focus on two main questions: whether the lesion is malignant, and whether it is hormonally active. Radiological evaluation including noncontrast and contrast computed tomography attenuation values expressed in Hounsfield units is the best tool to differentiate between benign and malignant adrenal masses. All adrenal tumors with suspicious radiological findings, most functional tumors, and all tumors more than 4 cm in size that lack characteristic benign imaging features should be surgically excised. All patients should undergo hormonal evaluation for subclinical Cushing's syndrome and pheochromocytoma, and those with hypertension should also be evaluated for hyperaldosteronism. Combined 1-mg dexamethasone suppression test, plasma metanephrines, and aldosterone/plasma renin activity measurements (if hypertensive) are reasonable initial hormonal evaluations. RESULTS: Annual biochemical follow-up of most patients with adrenal incidentalomas, especially if the tumor is more than 3 cm in size, for up to 5 yr may be reasonable. Patients with adrenal masses less than 4 cm in size and a noncontrast attenuation value of more than 10 Hounsfield units should have a repeat computed tomography study in 3-6 months and then yearly for 2 yr. Adrenal tumors with indeterminate radiological features that grow to at least 0.8 cm over 3-12 months may be considered for surgical resection. PubMed-ID: 21632813 http://dx.doi.org/10.1210/jc.2011-0085

Surgical Management of Incidental Adrenal Schwannom as. Am Surg, 77(5):E89-E90. Kleiman DA, Hughes DB, Joshi AR. 2011. PubMed-ID: 21679578

Laparoscopic Approach to Adrenalectomy: Review of P erioperative Outcomes in a Single Center. Am Surg, 77(5):592-6. Nguyen PH, Keller JE, Novitsky YW, Heniford BT, Kercher KW. 2011. Laparoscopic expertise increases the volume of adrenalectomies at referral centers. We report our 10-year experience with laparoscopic adrenalectomy. All laparoscopic adrenalectomies at a single institution were prospectively recorded in a surgical outcomes database. Patient demographics, operative/perioperative outcomes, and adrenal pathology were reviewed retrospectively. From March 1999 through July 2009, 154 laparoscopic adrenalectomies were performed in 150 patients. Average patient age was 49.9 years (range 15-82); mean body mass index was 31.1 kg/m(2) (range 17-56). Pathologic diagnoses included hyperaldosteronism (n = 69), nonfunctional adenoma (n = 28), pheochromocytoma (n = 23), hypercortisolism (n = 14), malignancy (primary n = 3, metastasis n = 9), and cyst (n = 4). Seventy-three per cent (n = 110) occurred on the left, 23 per cent (n = 35) on the right, 2.6 per cent (n = 4) bilateral, and 0.6 per cent (n = 1) as extra-adrenal. The average tumor measured 3.6 cm (range 0.4-12). The average operative time was 156 minutes (range 62-409), the mean estimated blood loss was 60 mL (range 10-400), and mean American Society of Anesthesiologists score was 2.6 (range 1-4). Three operations (0.2%) were converted to open. Three patients (0.2%) experienced perioperative complications (respiratory failure, urinary tract infection, line sepsis, and readmission within 30 days). The average length of stay was 3.4 days (range 1-44) and mean follow-up was 96.9 days (5-2567). No wound-related complications or deaths occurred. Pathologic diagnosis was not associated with a particular side or development of a complication (P > 0.5). Patients with pheochromocytomas had the longest operative times, highest estimated blood loss, and highest American Society of Anesthesiologists scores (218.2 minutes, 128 mL, 3.0; P < 0.004). Laparoscopic adrenalectomy is safe and effective. Removal of pheochromocytomas is more challenging and may be more appropriate for referral to a specialized center for optimal outcomes. PubMed-ID: 21679593


NET

Meta-Analyses Metaanalysis of Trials Comparing Minimally Invasive and Open Distal Pancreatectomies. Surg Endosc, 25(5):1642-51. Nigri GR, Rosman AS, Petrucciani N, Fancellu A, Pisano M, Zorcolo L, Ramacciato G, Melis M. 2011. BACKGROUND: The current literature suggests that minimally invasive distal pancreatectomy (MIDP) is associated with faster recovery and less morbidity than open surgery. However, most studies have been limited by a small sample size and a single-institution design. To overcome this problem, the first metaanalysis of studies comparing MIDP and open distal pancreatectomy (ODP) has been performed. METHODS: A systematic literature review was conducted to identify studies comparing MIDP and ODP. Perioperative outcomes (e.g., morbidity and mortality, pancreatic fistula rates, blood loss) constituted the study end points. Metaanalyses were performed using a random-effects model. RESULTS: For the metaanalysis, 10 studies including 349 patients undergoing MIDP and 380 patients undergoing ODP were considered suitable. The patients in the two groups were similar with respect to age, body mass index (BMI), American Society of Anesthesiology (ASA) classification, and indication for surgery. The rate of conversion from full laparoscopy to hand-assisted procedure was 37%, and that from minimally invasive to open procedure was 11%. Patients undergoing MIDP had less blood loss, a shorter time to oral intake, and a shorter postoperative hospital stay. The mortality and reoperative rates did not differ between MIDP and ODP. The MIDP approach had fewer overall complications [odds ratio (OR), 0.49; 95% confidence interval (CI), 0.27-0.89], major complications (OR, 0.57; 95% CI, 0.34-0.96), surgical-site infections (OR, 0.32; 95% CI, 0.19-0.53), and pancreatic fistulas (OR, 0.68; 95% CI, 0.47-0.98). CONCLUSIONS: The MIDP procedure is feasible, safe, and associated with less blood loss and overall complications, shorter time to oral intake, and shorter postoperative hospital stay. Furthermore, the minimally invasive approach reduces the rate of pancreatic leaks and surgical-site infections after ODP. PubMed-ID: 21184115 http://dx.doi.org/10.1007/s00464-010-1456-5

Role of Resection of the Primary Pancreatic Neuroen docrine Tumour Only in Patients With Unresectable Metastatic Liver Disease: a Systematic Review. Neuroendocrinology, 93(4):223-9. Capurso G, Bettini R, Rinzivillo M, Boninsegna L, Delle FG, Falconi M. 2011. BACKGROUND: Surgery remains the only curative option for pancreatic neuroendocrine tumours (PNETs), but its indication is limited by metastatic disease in most patients. Indication for removing the primary lesion only in the setting of unresectable liver disease is controversial. The present systematic review aims at determining the potential benefits (survival, progression-free survival) or harms (morbidity, mortality) of surgical resection of the primary lesion only in patients with PNETs and unresectable metastases. METHODS: Medline was queried for studies reporting the outcome of PNET patients with unresectable liver metastases whenever there was an explicit comparison between resection of the primary lesion only ('active treatment') and no resection ('non-active treatment'). The primary outcome was survival; possible secondary outcomes were progression-free survival, treatment-related mortality and morbidity, and relief of symptoms. RESULTS: Only 3 cohort studies found were eligible and analysed; no meta-analysis could be performed. The number of patients undergoing 'active treatment' varied from 16 to 20, with a percentage ranging from 17 to 39% of cohorts. Survival was longer in patients who received 'active treatment' in 2 studies, and the 5-year survival rate also seemed higher, without significant complications. DISCUSSION: Available data suggest a possible benefit of resection of the primary lesion only in this setting. However, a bias towards a more aggressive surgical approach in patients with a better performance status or less advanced disease seems likely, and no conclusion can be drawn except for the need of randomised trials. We calculated that such a trial would require at least 118 patients per arm. PubMed-ID: 21358176 http://dx.doi.org/10.1159/000324770



Other Articles [Pathology of Neuroendocrine Neoplasms] Pathologie Neuroendokriner Neoplasien. Chirurg, 82(7):567-73. Anlauf M, Gerlach P, Schott M, Raffel A, Krausch M, Knoefel WT, Pavel M, Kloppel G. 2011. During the last 5 years the European Neuroendocrine Tumor Society (ENETS) has developed basic recommendations for a standardized pathological diagnosis and classification of neuroendocrine neoplasms (NEN) of the gastroenteropancreatic system. These were included in the novel classification of tumors of the digestive system by the World Health Organization (WHO 2010) and the TNM classification of the union for international cancer control (2009). This review presents the pathology diagnosis regarding (1) basic diagnosis, (2) clinically relevant optional diagnosis, (3) proliferation-based grading, (4) nomenclature and (5) TNM classification. It is emphasized that a standardized diagnosis of NEN, together with clinical and radiological findings, is crucial for prognostic stratification and optimal therapy of patients with NEN. Therefore a close interdisciplinary collaboration is essential. PubMed-ID: 21487814 http://dx.doi.org/10.1007/s00104-011-2067-y

[Surgical Strategies for Accidental Detection of Ap pendix Carcinoids] Chirurgische Strategien Beim Zufallsbefund Eines Ap pendixkarzinoids. Chirurg, 82(7):598-606. Dralle H. 2011. Carcinoids (neuroendocrine tumors NET) of the appendix are rare tumors and even today mostly detected only postoperatively by histopathology following operations for acute appendicitis or other abdominal procedures. Most NETs of the appendix are located at the tip of the appendix, less than 2 cm in size and non-metastasizing. Secondary right hemicolectomy with lymph node dissection bears a considerable risk of complications compared to simple appendectomy. To decide upon secondary surgery histopathological risk factors, such as grading, invasion of the mesoappendix, and tumor type in addition to tumor localization and size should be taken into consideration. Up to 20% of NETs of the appendix are associated with various neoplasms of the gastrointestinal tract. Follow-up examination should therefore also consider both appendix carcinoids and synchronous or metachronous neoplasms of the gastrointestinal tract. PubMed-ID: 21491093 http://dx.doi.org/10.1007/s00104-011-2071-2

Hepatic Resection for the Carcinoid Syndrome in Pat ients With Severe Carcinoid Heart Disease: Does Valve Replacement Permit Safe Hepatic Resection? J Am Coll Surg, 213(1):130-6. Lillegard JB, Fisher JE, Mckenzie TJ, Que FG, Farnell MB, Kendrick ML, Donohue JH, Reid-Lombardo K, Schaff HV, Connolly HM, Nagorney DM. 2011. BACKGROUND: Hepatic resection of metastatic carcinoid cancer can prolong survival and control symptomatic endocrinopathy. Decompensated carcinoid heart disease (CHD) can develop in some patients with metastatic carcinoid cancers, which can preclude operation for resectable hepatic metastases. We hypothesized that outcomes after hepatic resection for patients with the carcinoid syndrome after valve replacement for CHD would be similar to carcinoid patients without CHD. STUDY DESIGN: We compared the survival and symptom control after hepatic resection for patients undergoing valve replacement for CHD to carcinoid patients without CHD matched for age, sex, and extent of hepatectomy. RESULTS: Fourteen patients with earlier valve replacement for CHD were compared with 28 carcinoid patients without CHD. All patients had hepatic resection for metastatic carcinoid disease and carcinoid syndrome. Mean age, sex distribution, and extent of hepatectomy (major hepatectomy, 78%) was similar between groups. Mean interval from valve replacement to hepatectomy was 101 days. There was no operative mortality. Major operative morbidity, inclusive of operative blood loss and cardiorespiratory events, occurred in 28.5% and 14.2% for CHD and non-CHD groups, respectively (p = 0.16). Symptom-free survival for CHD and non-CHD groups was 69% and 81% at 1 year (p = 0.22) and 61% and 44% (p = 0.17) at 5 years, respectively. Octreotide-free survival after hepatectomy 69% and 84% (p = 0.15) at 1 year and 62% and 52% (p = 0.29) 5 years, respectively. Overall survival CHD and non-CHD groups 100% at 1 year and 100% and 70% (p = 0.002) 5 years. CONCLUSIONS: Valve replacement for severe CHD is safe and hepatic resection is associated with similar outcomes as patients without CHD undergoing hepatic resection for carcinoid syndrome. Identifying resectable hepatic metastases from carcinoids in patients with severe CHD should prompt valve replacement and interval hepatic resection.


PubMed-ID: 21493110 http://dx.doi.org/10.1016/j.jamcollsurg.2011.03.029

Review of the Pathogenesis, Diagnosis, and Manageme nt of Type I Gastric Carcinoid Tumor. World J Surg, 35(8):1879-86. Zhang L, Ozao J, Warner R, Divino C. 2011. Gastric carcinoid tumors comprise 7% of all gastrointestinal carcinoids and have significantly increased in incidence over the past few decades. Seventy to 80% of gastric carcinoids are type I, which usually are clinically asymptomatic and found incidentally at endoscopic evaluation for abdominal pain or anemia. In this review, advances in understanding the pathophysiology of type I gastric carcinoid are highlighted. In addition, various current diagnostic and treatment options are discussed. Although type I carcinoids generally hold a benign course, rigorous investigation is needed to ensure accurate diagnosis and optimal treatment. This includes appropriate diagnostic procedures and imaging and accurate staging of tumor. Tumor size, depth of invasion, presence of metastasis, and the tumor's gastrin dependency dictate treatment options. Appropriate treatments can consist of endoscopic resection, antrectomy, medical management, or frequent follow-up. This article provides a systematic method of evaluating and treating type I gastric carcinoid. PubMed-ID: 21559999 http://dx.doi.org/10.1007/s00268-011-1137-0

[Neuroendocrine Tumors. More Variety Than Uniformit y] Neuroendokrine Tumoren. Mehr Vielfalt Als Einheitli chkeit. Chirurg, 82(7):565-6. Dralle H. 2011. PubMed-ID: 21603959 http://dx.doi.org/10.1007/s00104-010-2064-6

Modern PET Imaging for Paragangliomas: Relation to Genetic Mutations. Eur J Surg Oncol, 37(8):662-8. Taieb D, Rubello D, Al-Nahhas A, Calzada M, Marzola MC, Hindie E. 2011. AIM AND METHODS: Paragangliomas (PGL) are neural crest-derived tumours that are found along the autonomic neural network throughout the body and can be multiple and/or metastatic. Nuclear medicine imaging in combination with conventional imaging is required to fully delineate the extent of the disease. The performance of molecular imaging modalities is widely dependent on tumour biology. RESULTS: In the present paper we discuss the recent publications focused on the role of positron emission tomography (PET) imaging and the relationship between tracer uptake patterns and genetic mutations associated with the disease. CONCLUSION: Recent advances in genetic and molecular pathogenesis of PGL have allowed for the identification of new molecular diagnostic and therapeutic radiopharmaceuticals tailored to genetic abnormalities. However, the optimal diagnostic imaging algorithm remains to be determined. PubMed-ID: 21636242 http://dx.doi.org/10.1016/j.ejso.2011.05.004

[Neuroendocrine Colorectal Tumors. Surgical and End oscopic Treatment] Neuroendokrine Kolorektale Tumoren. Chirurgische Un d Endoskopische Therapieverfahren. Chirurg, 82(7):607-11. Hotz HG, Bojarski C, Buhr HJ. 2011. The incidence of colorectal neuroendocrine tumors (NETs) is rising in developed countries primarily as a result of increased incidental detection by endoscopy and probably also due to a more adequate diagnosis according to the WHO classification. Less than 1% of colorectal NETs produce serotonin so that such tumors are practically never associated with a hormonal carcinoid syndrome. An exact clinico-pathological staging is of paramount importance for the therapeutic strategy and comprises the classification of the tumor type (well or poorly differentiated) and the assessment of established prognostic risk factors (depth of infiltration, vascular invasion, lymph node and distant metastases). Poorly differentiated colorectal NETs often present in an advanced, metastatic state, where surgical therapy is basically palliative. Well-differentiated tumors larger than 2 cm have a high risk of metastatic spread and should be treated as adenocarcinomas by radical oncological surgical resection. This applies to the majority of colon NETs. Tumors smaller than 1 cm, mainly locacted in the rectum, only rarely metastasize and are usually accessible for endoscopic treatment or transanal local surgery. Tumors between 1 and 2 cm in size have an uncertain prognosis and additional risk factors and co-morbidities of the patient have to be considered for a suitable, multidisciplinary therapeutic decision.


PubMed-ID: 21656304 http://dx.doi.org/10.1007/s00104-011-2072-1

[Neuroendocrine Tumors of the Duodenum and Pancreas . Surgical Strategy] Neuroendokrine Tumoren Des Duodenums Und Pankreas. Chirurgische Strategie. Chirurg, 82(7):583-90. Fischer L, Mehrabi A, Buchler MW. 2011. The incidence of neuroendocrine tumors (NET) has increased worldwide by 3-5 times over the last decades. This is mainly based on the broad use of imaging modalities such as computed tomography (CT) and endoscopic approaches. As a consequence many duodenal and pancreatic tumors are detected in an early stage resulting in an improved prognosis of these patients. Besides the measurement of serum chromogranin A and 5-hydroxy indolic acid measured in 24 h urine collection, CT, endosonographic ultrasound (EUS) and endoscopy are important diagnostic tools. About 20% of all patients with pancreatic and duodenal NETs are diagnosed because of specific symptoms. More than 95% of diagnosed NETs are sporadic tumors. Whenever possible these patients should be treated by resection. Benign neuroendocrine duodenal tumors up to 1 cm in size can be removed endoscopically. The endoscopic resection of larger tumors should be performed surgically. The therapy of hereditary NETs of the duodenum and the pancreas should be decided after interdisciplinary discussion. However, even these patients seem to benefit from resection. In case of metastatic disease debulking surgery should be considered if more than 90% of the tumor mass can be resected. In patients with extensive liver metastases but resectable primary NET, liver transplantation is a reasonable option. There is no consensus about adjuvant or neoadjuvant treatment of duodenal or pancreatic NETs. The therapy with everolimus or sunitinib in advanced tumor stages has shown promising results. The administration of somatostatin analogues or antacids is appropriate for symptom reduction. PubMed-ID: 21656305 http://dx.doi.org/10.1007/s00104-011-2069-9

[Extent of Resection for Neuroendocrine Tumors of t he Small Intestine] Resektionsausmass Bei Neuroendokrinen Tumoren Des D unndarms. Chirurg, 82(7):591-7. Musholt TJ. 2011. Neuroendocrine tumors of the small intestine have been diagnosed with increasing frequency over the past 35 years and presently account for approximately 2% of all gastrointestinal neoplasms. While most of these tumors are discovered incidentally during emergency laparotomy or in the clinical setting of unknown primary cancer with hepatic metastases, the growing awareness of this rare entity and improved diagnostic methods promote earlier diagnosis. The classical carcinoid syndrome with flush, diarrhea and cardiac strain is observed only in 20-30% of patients. The clinical symptoms necessitate a special preoperative preparation of the patient including evaluation of cardiac function.Prospective studies assessing the efficacy of surgical treatment strategies for neuroendocrine neoplasms of the small intestine do not exist. However, retrospective studies have demonstrated that curative as well as palliative resection of the primary tumor improves the prognosis and the quality of life of patients. Besides limited resection of the small bowel in order to avoid postoperative short bowel syndrome an effective clearance of the regional lymph nodes is essential. A primary tumor site in the terminal ileum requires dissection of the lymph nodes on the right side of the ileocolic artery which usually implies an additional resection of the right colon. In cases of a primary tumor site located in the lower ileum up to the distal jejunum, a cone-shaped resection of the mesenterium of the small bowel with extension of lymphadenectomy into adjacent segments with preservation of vascularization is performed. PubMed-ID: 21678105 http://dx.doi.org/10.1007/s00104-011-2070-3

Pancreatic Endocrine Tumors With Major Vascular Abu tment, Involvement, or Encasement and Indication for Resection. Arch Surg, 146(6):724-32. Norton JA, Harris EJ, Chen Y, Visser BC, Poultsides GA, Kunz PC, Fisher GA, Jensen RT. 2011. BACKGROUND: Surgery for pancreatic endocrine tumors (PETs) with blood vessel involvement is controversial. HYPOTHESIS: Resection of PETs with major blood vessel involvement can be beneficial. DESIGN: The combined databases of the National Institutes of Health and Stanford University hospitals were queried. MAIN OUTCOME MEASURES: Operation, pathologic condition, complications, and disease-free and overall survival. RESULTS: Of 273 patients with PETs, 46 (17%) had preoperative computed tomography evidence of major vascular involvement. The mean size for the primary PET was 5.0 cm. The involved major vessel was as follows: portal vein (n = 20), superior mesenteric vein or superior mesenteric artery (n = 16), inferior vena cava (n = 4),


splenic vein (n = 4), and heart (n = 2). Forty-two of 46 patients had a PET removed: 12 (27%) primary only, 30 (68%) with lymph nodes, and 18 (41%) with liver metastases. PETs were removed by either enucleation (n = 7) or resection (n = 35). Resections included distal or subtotal pancreatectomy in 23, Whipple in 10, and total in 2. Eighteen patients had concomitant liver resection: 10 wedge resection and 8 anatomic resections. Nine patients had vascular reconstruction: each had reconstruction of the superior mesenteric vein and portal vein, and 1 had concomitant reconstruction of the superior mesenteric artery. There were no deaths, but 12 patients had complications. Eighteen patients (41%) were immediately disease free, and 5 recurred with follow-up, leaving 13 (30%) disease-free long term. The 10-year overall survival was 60%. Functional tumors were associated with a better overall survival (P < .001), and liver metastases decreased overall survival (P < .001). CONCLUSION: These findings suggest that surgical resection of PETs with vascular abutment/invasion and nodal or distant metastases is indicated. PubMed-ID: 21690450 http://dx.doi.org/10.1001/archsurg.2011.129

[Gastric Neuroendocrine Tumors. Endoscopic and Surg ical Treatment] Neuroendokrine Tumoren Des Magens. Endoskopische Un d Chirurgische Therapie. Chirurg, 82(7):574-82. Niederle MB, Niederle B. 2011. Neuroendocrine tumors (NETs) of the stomach are the most frequent among all neuroendocrine neoplasms in the digestive tract. The diagnosis and classification are complicated by the fact that these tumors have to be categorized not only by common staging and grading but also according to their pathophysiological background (types). The types differ in their biological behaviour (aggressiveness) which influences therapeutic concepts. This article explains and summarizes the etiology and classification of gastric NETs and offers a precise concept for diagnosis and treatment to improve clinical outcome. PubMed-ID: 21691871 http://dx.doi.org/10.1007/s00104-011-2068-x

[Metastatic Neuroendocrine Neoplasms. Non-Surgical Treatment Strategies] Metastasierte Neuroendokrine Neoplasien. Nichtopera tive Therapiekonzepte. Chirurg, 82(7):612-7. Pavel M. 2011. The clinical presentation of neuroendocrine neoplasms (NEN) varies depending on the site of origin, functional activity, histological differentiation and tumor growth behavior. Therapeutic strategies aim to improve the symptoms of clinical syndromes related to the secretion of amines and peptides, inhibit tumor growth and prevent complications. Novel molecular targeted drug therapies offer new treatment options in addition to established therapies, such as somatostatin analogs and chemotherapy. The precise positioning of these drugs and of peptide receptor radionuclide therapy still needs to be defined. In general, the different medical treatments are used in a sequential way and are in part combined with surgical and loco-regional/ablative procedures in a highly individualized approach. In certain clinical conditions, however, established treatment strategies are followed. This review presents the management of patients with small intestinal and pancreatic NEN with respect to the functionality and tumor grading. The use of novel targeted drug therapy is included in a therapeutic algorithm. PubMed-ID: 21735357 http://dx.doi.org/10.1007/s00104-011-2073-0

Incidentally, It's Still Cancer. Arch Surg, 146(5):539. Vollmer CM, Jr. 2011. PubMed-ID: 21739652

Appendiceal Carcinoid at a Large Tertiary Center: P athologic Findings and Long-Term Follow-Up Evaluation. Am J Surg, 201(6):805-8. Shapiro R, Eldar S, Sadot E, Papa MZ, Zippel DB. 2011. BACKGROUND: Appendiceal carcinoid tumor is the most common type of primary appendiceal malignant lesion. Nonetheless; it is an exceedingly rare diagnosis; found in only about .3% to .9% of appendectomy specimens. We report the clinical and pathologic characteristics of carcinoids found with long-term follow-up evaluation. METHODS: Data of patients who were histologically reported to have carcinoid tumor of the appendix; in a single center; during a 16-year period were collected retrospectively. In addition; patients were


contacted for current follow-up information. RESULTS: A total of 44 patients were diagnosed with appendiceal carcinoid during the study period. The median follow-up period for the cohort was 7 years. No evidence of any recurrent disease or other noncarcinoid neoplasm was found. CONCLUSIONS: Our data confirm the good prognosis as seen in earlier reports. The long-term significance of having a carcinoid; and whether this poses a risk for future neoplasms; need even longer-term studies. PubMed-ID: 21741512 http://dx.doi.org/10.1016/j.amjsurg.2010.04.016


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