ESES Review of Recently Published Literature

Collection: T. Clerici1, T.  Defechereux, F. Triponez2
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

Ulrich.beutner@kssg.ch

May - Aug 2012
Data retrival from Pubmed: 11. Dec 2012
Contents
CTRL-click on title jumps to the according page

	Publication count:	SR/MA 	RCT	Other	Page
Thyroid	3	6	98	2
Parathyroid	0	0	37	44
Adrenals	0	2	19	58
NET	1	0	11	66
GI and General	0	0	3	71
Papers of the Intern. Assoc. of Endocrine Surgery – ISW 2011, World J Surgery, Volume 36, Issue 6	73

SR: systematic review, MA: meta-analysis, RCT: randomized controlled trial
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).

Thyroid
Meta-Analyses
The Bethesda System for Reporting Thyroid Cytopathology: a Meta-Analysis.
Acta Cytol, 56(4):333-9.
Bongiovanni M, Spitale A, Faquin WC, Mazzucchelli L, Baloch ZW. 2012.
OBJECTIVE: We aimed to investigate the validity of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) through meta-analysis. STUDY DESIGN: All publications between January 1, 2008 and September 1, 2011 that studied TBSRTC and had available histological follow-up data were retrieved. To calculate the sensitivity, specificity and diagnostic accuracy, the cases diagnosed as follicular neoplasm, suspicious for malignancy and malignant which were histopathologically confirmed as malignant were defined as true-positive. True-negative included benign cases confirmed as benign on histopathology. The nondiagnostic category was excluded from the statistical calculation. The correlations between the 6 diagnostic categories were investigated. RESULTS: The publications review resulted in a case cohort of 25,445 thyroid fine-needle aspirations, 6,362 (25%) of which underwent surgical excision; this group constituted the basis of the study. The sensitivity, specificity and diagnostic accuracy were 97, 50.7 and 68.8%, respectively. The positive predictive value and negative predictive value were 55.9 and 96.3%, respectively. The rates of false negatives and false positives were low: 3 and 0.5%, respectively. CONCLUSIONS: The results of meta-analysis showed high overall accuracy, indicating that TBSRTC represents a reliable and valid reporting system for thyroid cytology.
PubMed-ID: 22846422
http://dx.doi.org/10.1159/000339959
Risk of Hypothyroidism Following Hemithyroidectomy: Systematic Review and Meta-Analysis of Prognostic Studies.
J Clin Endocrinol Metab, 97(7):2243-55.
Verloop H, Louwerens M, Schoones JW, Kievit J, Smit JW, Dekkers OM. 2012.
CONTEXT: The reported risk of hypothyroidism after hemithyroidectomy shows considerable heterogeneity in literature. OBJECTIVE: The aim of this systematic review and meta-analysis was to determine the overall risk of hypothyroidism, both clinical and subclinical, after hemithyroidectomy. Furthermore, we aimed to identify risk factors for postoperative hypothyroidism. DATA SOURCES: A systematic literature search was performed using several databases, including PubMed. STUDY SELECTION: Original articles in which an incidence or prevalence of hypothyroidism after primary hemithyroidectomy could be extracted were included. DATA EXTRACTION: Study identification and data extraction were performed independently by two reviewers. In case of disagreement, a third reviewer was consulted. DATA SYNTHESIS: A total of 32 studies were included in this meta-analysis. Meta-analysis was performed using logistic regression with random effect at study level. The overall risk of hypothyroidism after hemithyroidectomy was 22% (95% confidence interval, 19-27). A clear distinction between clinical (supranormal TSH levels and subnormal thyroid hormone levels) and subclinical (supranormal TSH levels and thyroid hormone levels within the normal range) hypothyroidism was provided in four studies. These studies reported on an estimated risk of 12% for subclinical hypothyroidism and 4% for clinical hypothyroidism. Positive anti-thyroid peroxidase status is a relevant preoperative indicator of hypothyroidism after surgery. Effect estimates did not differ substantially between studies with lower risk of bias and studies with higher risk of bias. CONCLUSIONS: This meta-analysis showed that approximately one in five patients will develop hypothyroidism after hemithyroidectomy, with clinical hypothyroidism in one of 25 operated patients.
PubMed-ID: 22511795
http://dx.doi.org/10.1210/jc.2012-1063
The Utility of Serum Thyroglobulin Measurement at the Time of Remnant Ablation for Predicting Disease-Free Status in Patients With Differentiated Thyroid Cancer: a Meta-Analysis Involving 3947 Patients.
J Clin Endocrinol Metab, 97(8):2754-63.
Webb RC, Howard RS, Stojadinovic A, Gaitonde DY, Wallace MK, Ahmed J, Burch HB. 2012.
CONTEXT: Decisions regarding initial therapy and subsequent surveillance in patients with differentiated thyroid cancer (DTC) depend upon an accurate assessment of the risk of persistent or recurrent disease. OBJECTIVE: The objective of this study was to examine the predictive value of a single measurement of serum thyroglobulin (Tg) just before radioiodine remnant ablation (preablation Tg) on subsequent disease-free status. DATA SOURCES: Sources included MEDLINE and BIOSYS databases between January 1996 and June 2011 as well as data from the author's tertiary-care medical center. STUDY SELECTION: Included studies reported preablation Tg values and the outcome of initial therapy at surveillance testing or during the course of long-term follow-up. DATA EXTRACTION: Two investigators independently extracted data and rated study quality using the Quality Assessment of Studies of Diagnostic Accuracy included in Systematic Reviews-2 (QUADAS-2) tool. DATA SYNTHESIS: Fifteen studies involving 3947 patients with DTC were included. Seventy percent of patients had preablation Tg values lower than the threshold value being examined. The negative predictive value (NPV) of a preablation Tg below threshold was 94.2 (95% confidence interval = 92.8-95.3) for an absence of biochemical or structural evidence of disease at initial surveillance or subsequent follow-up. The summary receiver operator characteristic curve based on a bivariate mixed-effects binomial regression model showed a clustering of studies using a preablation Tg below 10 ng/ml near the summary point of optimal test sensitivity and specificity. CONCLUSION: Preablation Tg testing is a readily available and inexpensive tool with a high NPV for future disease-free status. A low preablation Tg should be considered a favorable risk factor in patients with DTC. Further study is required to determine whether a low preablation Tg may be used to select patients for whom radioiodine remnant ablation can be avoided.
PubMed-ID: 22639291
http://dx.doi.org/10.1210/jc.2012-1533
Randomized controlled trials
Combination of Dexamethasone and Tropisetron Before Thyroidectomy to Alleviate Postoperative Nausea, Vomiting, and Pain: Randomized Controlled Trial.
World J Surg, 36(6):1217-24.
Zhou H, Xu H, Zhang J, Wang W, Wang Y, Hu Z. 2012.
BACKGROUND: Nausea, vomiting, and pain frequently occur after thyoidectomy. Little evidence exists regarding the effects of administrating a combination of dexamethasone and tropisetron to patients undergoing thyroidectomy. We aimed to evaluate the effects of dexamethasone and tropisetron on thyroidectomy outcomes. METHODS: A total of 150 patients undergoing thyroidectomy were included in this prospective randomized, controlled, three-arm study (group D: 8 mg dexamethasone; group T: 5 mg tropisetron; group D+T: 8 mg dexamethasone and 5 mg tropisetron). There were 50 patients in each group. Nausea, vomiting, pain, and the amount of antiemetic and analgesic agents required were recorded 2, 4, 8, 16, 24, 36, and 48 h postoperatively. RESULTS: The complete response rate of nausea and vomiting was significantly higher in group D+T (78%, 39/50), compared with that in group D (58%, 29/50) or group T (66%, 33/50) (P = 0.01). The incidence and severity of nausea in group D+T were significantly lower than in group D and group T, with the difference mainly occurring in the late postoperative period (6-48 h). The severity of postoperative pain was significantly less in the dexamethasone-containing groups (D and D+T groups) than in the tropisetron group. CONCLUSIONS: The combination of dexamethasone and tropisetron offers better prophylaxis for nausea, vomiting, and pain than either drug alone in patients undergoing thyroidectomy, especially during the late period (6-48 h).
PubMed-ID: 22146946
http://dx.doi.org/10.1007/s00268-011-1363-5
The Safety of Energy-Based Devices in Open Thyroidectomy: a Prospective, Randomised Study Comparing the LigaSure (LF1212) and the Harmonic(R) FOCUS.
Langenbecks Arch Surg, 397(5):817-23.
Dionigi G, Boni L, Rausei S, Frattini F, Ferrari CC, Mangano A, Leotta A, Franchin M. 2012.
PURPOSE: The options for haemostasis and dissection during modern thyroid surgery include the use of a bipolar vessel sealing system and ultrasonic technology. The aim of this study was to compare these energy-based devices (EBDs) with respect to their use in open thyroidectomy. METHODS: The FOCUS Shear (F) and LigaSure LF1212 (L) were evaluated. A total of 182 consecutive patients scheduled for open thyroidectomy were prospectively randomised into two similarly sized groups. The parameters of operative time, morbidity, incision length, postoperative pain and hospital stay were analysed. RESULTS: The main clinically primary endpoints of the two devices were identical in the study as the rate of nerve lesions, bleeding, drainage, operative time and postoperative calcium concentration with no significant differences with respect to the instrument utilised. The mean length of the incision was greater in the F group (p < 0.05). Patients in the F group were more likely to complain of pain while swallowing (p < 0.001). Early postoperative measurements of intact parathyroid hormone plasma levels revealed that although the levels were within the reference range, they were significantly lower in the F group (p < 0.001). Oral calcium supplementation was significantly higher and more prolonged in the F group. CONCLUSIONS: The present study demonstrated no significant difference in the rates of postoperative morbidity associated with these two different EBDs used. Differences in clinically less significant were founded and focused on.
PubMed-ID: 22230963
http://dx.doi.org/10.1007/s00423-011-0898-0
Total Thyroidectomy With Ultrasonic Scalpel: a Multicenter, Randomized Controlled Trial.
Head Neck, 34(6):805-12.
Kowalski LP, Sanabria A, Vartanian JG, Lima RA, de Mendonca UB, dos Santos CR, Boldrini D, Jr., de Mello LE, Pinto FP, Lehn CN, Correa LA, Dedivitis RA, Guimaraes AV, Pedruzzi PA, Ramos GH, Goncalves AJ, Suehara AB, Kanda JL, Capuzzo RC, de Oliveira JC, Curado MP, de Gois Filho JF, Fukuyama E, Beserra IM, Jr., de Carvalho Neto PB, Carvalho AL. 2012.
BACKGROUND: The ultrasonic scalpel is a recently introduced device in head and neck surgery. Total thyroidectomy is the most common endocrine procedure performed by surgeons. METHODS: This was an open, phase IV, multicenter, randomized controlled trial (RCT) that compared the use of an ultrasonic scalpel with a conventional technique in patients who underwent total thyroidectomy. The outcomes were surgical complication rate, operative time, drainage volume, postoperative pain, and costs. RESULTS: In all, 261 patients were included in 11 centers. There was a mean difference of 17% of operative time in favor of the ultrasonic scalpel group. There were no differences in postoperative complications. There was a difference in costs of 14% in favor of the ultrasonic scalpel group, but it was not statistically significant. CONCLUSIONS: The use of an ultrasonic scalpel was as safe as that of the conventional technique and had the advantage of a shorter operative time and lower postoperative drainage. Costs were not different between groups.
PubMed-ID: 22302518
http://dx.doi.org/10.1002/hed.21815
Randomized Controlled Trial of Visualization Versus Neuromonitoring of the External Branch of the Superior Laryngeal Nerve During Thyroidectomy.
World J Surg, 36(6):1340-7.
Barczynski M, Konturek A, Stopa M, Honowska A, Nowak W. 2012.
BACKGROUND: Injury to the external branch of the superior laryngeal nerve (EBSLN) during thyroidectomy results in a lowered fundamental frequency of the voice and deteriorated voice performance in producing high-frequency sounds. It remains unclear if the use of intraoperative nerve monitoring (IONM) can improve the clinical outcome of thyroidectomy in terms of preserved individual voice performance. This study was designed to test that hypothesis. METHODS: A total of 210 consenting female patients planned for total thyroidectomy were randomly assigned to two groups equal in size (n = 105): visual inspection of the EBSLN and RLN vs. this plus additional EBSLN and RLN monitoring. The primary outcome was the identification rate of the EBSLN. The secondary outcomes included: anatomical variability of the EBSLN according to the Cernea classification and changes in postoperative voice performance. Voice assessment included pre- and postoperative videostrobolaryngoscopy and an analysis of maximum phonation time (MPT), voice level (VL), fundamental frequency (Fo), and voice quality rating on the GRBAS scale. RESULTS: The following differences were found for operations without vs. with IONM: identification rate of the EBSLN was 34.3 % vs. 83.8 % (p < 0.001), whereas a 10 % or higher decrease in phonation parameters was found in 10 % vs. 2 % patients for MPT (p = 0.018), 13 % vs. 2 % for VL (p = 0.003), and 9 % vs. 1 % for Fo (p = 0.03), a change in the GRBAS scale > 4 points in 7 % vs. 1 % (p = 0.03), and temporary RLN injury was found in 2 % vs. 1 % (p = 0.56), respectively. CONCLUSIONS: The use of IONM significantly improved the identification rate of the EBSLN during thyroidectomy, as well as reduced the risk of early phonation changes after thyroidectomy.
PubMed-ID: 22402975
http://dx.doi.org/10.1007/s00268-012-1547-7
Strategies of Radioiodine Ablation in Patients With Low-Risk Thyroid Cancer.
N Engl J Med, 366(18):1663-73.
Schlumberger M, Catargi B, Borget I, Deandreis D, Zerdoud S, Bridji B, Bardet S, Leenhardt L, Bastie D, Schvartz C, Vera P, Morel O, Benisvy D, Bournaud C, Bonichon F, Dejax C, Toubert ME, Leboulleux S, Ricard M, Benhamou E. 2012.
BACKGROUND: It is not clear whether the administration of radioiodine provides any benefit to patients with low-risk thyroid cancer after a complete surgical resection. The administration of the smallest possible amount of radioiodine would improve care. METHODS: In our randomized, phase 3 trial, we compared two thyrotropin-stimulation methods (thyroid hormone withdrawal and use of recombinant human thyrotropin) and two radioiodine ((131)I) doses (i.e., administered activities) (1.1 GBq and 3.7 GBq) in a 2-by-2 design. Inclusion criteria were an age of 18 years or older; total thyroidectomy for differentiated thyroid carcinoma; tumor-node-metastasis (TNM) stage, ascertained on pathological examination (p) of a surgical specimen, of pT1 (with tumor diameter </=1 cm) and N1 or Nx, pT1 (with tumor diameter >1 to 2 cm) and any N stage, or pT2N0; absence of distant metastasis; and no iodine contamination. Thyroid ablation was assessed 8 months after radioiodine administration by neck ultrasonography and measurement of recombinant human thyrotropin-stimulated thyroglobulin. Comparisons were based on an equivalence framework. RESULTS: There were 752 patients enrolled between 2007 and 2010; 92% had papillary cancer. There were no unexpected serious adverse events. In the 684 patients with data that could be evaluated, ultrasonography of the neck was normal in 652 (95%), and the stimulated thyroglobulin level was 1.0 ng per milliliter or less in 621 of the 652 patients (95%) without detectable thyroglobulin antibodies. Thyroid ablation was complete in 631 of the 684 patients (92%). The ablation rate was equivalent between the (131)I doses and between the thyrotropin-stimulation methods. CONCLUSIONS: The use of recombinant human thyrotropin and low-dose (1.1 GBq) postoperative radioiodine ablation may be sufficient for the management of low-risk thyroid cancer. (Funded by the French National Cancer Institute [INCa] and the French Ministry of Health; ClinicalTrials.gov number, NCT00435851; INCa number, RECF0447.).
PubMed-ID: 22551127
http://dx.doi.org/10.1056/NEJMoa1108586
Ablation With Low-Dose Radioiodine and Thyrotropin Alfa in Thyroid Cancer.
N Engl J Med, 366(18):1674-85.
Mallick U, Harmer C, Yap B, Wadsley J, Clarke S, Moss L, Nicol A, Clark PM, Farnell K, McCready R, Smellie J, Franklyn JA, John R, Nutting CM, Newbold K, Lemon C, Gerrard G, Abdel-Hamid A, Hardman J, Macias E, Roques T, Whitaker S, Vijayan R, Alvarez P, Beare S, Forsyth S, Kadalayil L, Hackshaw A. 2012.
BACKGROUND: It is not known whether low-dose radioiodine (1.1 GBq [30 mCi]) is as effective as high-dose radioiodine (3.7 GBq [100 mCi]) for treating patients with differentiated thyroid cancer or whether the effects of radioiodine (especially at a low dose) are influenced by using either recombinant human thyrotropin (thyrotropin alfa) or thyroid hormone withdrawal. METHODS: At 29 centers in the United Kingdom, we conducted a randomized noninferiority trial comparing low-dose and high-dose radioiodine, each in combination with either thyrotropin alfa or thyroid hormone withdrawal before ablation. Patients (age range, 16 to 80 years) had tumor stage T1 to T3, with possible spread to nearby lymph nodes but without metastasis. End points were the rate of success of ablation at 6 to 9 months, adverse events, quality of life, and length of hospital stay. RESULTS: A total of 438 patients underwent randomization; data could be analyzed for 421. Ablation success rates were 85.0% in the group receiving low-dose radioiodine versus 88.9% in the group receiving the high dose and 87.1% in the thyrotropin alfa group versus 86.7% in the group undergoing thyroid hormone withdrawal. All 95% confidence intervals for the differences were within +/-10 percentage points, indicating noninferiority. Similar results were found for low-dose radioiodine plus thyrotropin alfa (84.3%) versus high-dose radioiodine plus thyroid hormone withdrawal (87.6%) or high-dose radioiodine plus thyrotropin alfa (90.2%). More patients in the high-dose group than in the low-dose group were hospitalized for at least 3 days (36.3% vs. 13.0%, P<0.001). The proportions of patients with adverse events were 21% in the low-dose group versus 33% in the high-dose group (P=0.007) and 23% in the thyrotropin alfa group versus 30% in the group undergoing thyroid hormone withdrawal (P=0.11). CONCLUSIONS: Low-dose radioiodine plus thyrotropin alfa was as effective as high-dose radioiodine, with a lower rate of adverse events. (Funded by Cancer Research UK; ClinicalTrials.gov number, NCT00415233.).
PubMed-ID: 22551128
http://dx.doi.org/10.1056/NEJMoa1109589
Other Articles
Thyroid Cancer Detection With Dual-Isotope Parathyroid Scintigraphy in Primary Hyperparathyroidism.
Ann Surg Oncol, 19(5):1446-52.
Onkendi EO, Richards ML, Thompson GB, Farley DR, Peller PJ, Grant CS. 2012.
BACKGROUND: Thyroid cancer cells have been shown to take up (99m)Tc-sestamibi. The role for (99m)Tc-sestamibi scintigraphy (Tc-MIBI) in the diagnosis of thyroid cancer in patients with primary hyperparathyroidism (PHPT) is unclear. Our aim was to determine whether dual-isotope parathyroid scintigraphy is useful in identifying thyroid cancer. METHODS: A prospective database of 3,187 patients who underwent neck exploration for PHPT was reviewed to identify patients who had concurrent thyroid resection. Patients with benign and malignant thyroid disease were comparatively analyzed. RESULTS: A total of 470 patients underwent both thyroidectomy and parathyroidectomy (reoperations in 21%). Benign disease (n = 391, 83%) was more common than malignancy [papillary thyroid cancer (n = 75) and medullary thyroid cancer (n = 5); 1 had both]. Dual-isotope scintigraphy obtained in 374 patients (80%) had a sensitivity of 67% and a positive predictive value of 66% for parathyroid adenoma localization in these patients with thyroid disease. False-positive scintigraphy occurred in 22% with benign and 45% with malignant thyroid disease (P = 0.002). On Tc-MIBI imaging, 54 (86%) of 63 patients with malignancy had hot nodules, compared to 248 (81%) of 308 patients with benign disease (P = 0.49). On I-123 imaging, 34 (54%) of 63 patients with malignancy had cold nodules, compared to 42 (14%) of 304 patients with benign disease (P < 0.001). A dual-isotype phenotype of both Tc-MIBI-Hot and I-123-Cold had sensitivity 52%, specificity 88%, positive predictive value 47%, and negative predictive value 90% for detecting a thyroid malignancy. CONCLUSIONS: A Tc-MIBI-Hot/I-123-Cold phenotype is very specific for detecting thyroid malignancy. Patients with this imaging phenotype should strongly be considered for preoperative ultrasound-guided biopsy. Patients found intraoperatively to have false-positive parathyroid scintigraphy should be evaluated for thyroid cancer.
PubMed-ID: 22395991
http://dx.doi.org/10.1245/s10434-012-2282-x
Novel Molecular Targeted Therapies for Refractory Thyroid Cancer.
Head Neck, 34(5):736-45.
Perez CA, Santos ES, Arango BA, Raez LE, Cohen EE. 2012.
The incidence of thyroid cancer continues to increase and this neoplasia remains the most common endocrine malignancy. No effective systemic treatment currently exists for iodine-refractory differentiated or medullary thyroid carcinoma, but recent advances in the pathogenesis of these diseases have revealed key targets that are now being evaluated in the clinical setting. RET (rearranged during transfection)/PTC (papillary thyroid carcinoma) gene rearrangements, B-Raf gene mutations, and vascular endothelial growth factor receptor 2 (VEGFR-2) angiogenesis pathways are some of the known genetic alterations playing a crucial role in the development of thyroid cancer. Several novel agents have demonstrated promising responses. Of the treatments studied, multi-kinase inhibitors such as axitinib, sorafenib, motesanib, and XL-184 have shown to be the most effective by inducing clinical responses and stabilizing the disease process. Randomized clinical trials are currently evaluating these agents, results that may soon change the management of thyroid cancer.
PubMed-ID: 21544895
http://dx.doi.org/10.1002/hed.21755
Early Surgical Outcomes of Robotic Thyroidectomy by a Gasless Unilateral Axillo-Breast or Axillary Approach for Papillary Thyroid Carcinoma: 2 Years' Experience.
Head Neck, 34(5):617-25.
Tae K, Ji YB, Cho SH, Lee SH, Kim DS, Kim TW. 2012.
BACKGROUND: The efficacy of robotic thyroidectomy for thyroid cancer has not yet been assessed. The aim of this study was to evaluate the technical feasibility and completeness of robotic thyroidectomy for papillary thyroid carcinoma (PTC). METHODS: We analyzed 75 patients with PTC who underwent robotic thyroidectomy from October 2008 to August 2010 using a gasless unilateral axillo-breast or axillary approach with a da Vinci S Surgical System Robot and compared them with 226 patients who received conventional open thyroidectomy. RESULTS: The robotic thyroidectomy procedure was successfully completed in all the patients. The complication rate did not differ between the 2 groups, except for transient hypoparathyroidism. The surgical completeness of robotic thyroidectomy was comparable to that of conventional open thyroidectomy, and cosmetic satisfaction was superior in the robotic group. CONCLUSION: Robotic thyroidectomy is a safe, feasible, and cosmetically excellent procedure in properly selected patients with PTC.
PubMed-ID: 21688343
http://dx.doi.org/10.1002/hed.21782
Functional Capacity of the Thyroid Autograft and Heterograft: An Experimental Study.
Head Neck, 34(5):702-8.
Karaman M, Tuncel A, Sheidaei S, Karabulut MH, Tatlipinar A. 2012.
BACKGROUND: The aim of this study was to investigate the functional capacity of thyroid autografts/heterografts in a guinea pig model. METHODS: A total of 24 guinea pigs were divided into 4 groups. Group A had only a thyroidectomy incision, and group B had total thyroidectomy. We performed autotransplantation in group C and heterotransplantation in group D. We monitored the guinea pigs for an 8-week period, with weekly measurements of free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH). At the final stage, the autografts/heterografts were histologically examined. RESULTS: In group B, fT3/fT4 showed a gradual decrease; however, an increase of TSH was noted. In groups C and D, fT3/fT4 showed a gradual decrease, followed by a gradual increase until euthyroid levels; an exact opposite was noted for TSH. In histologic examination, there were functional thyroid follicles in all animals of groups C and D. CONCLUSIONS: The autotransplanted/heterotransplanted guinea pig's thyroid tissue provides adequate thyroid function.
PubMed-ID: 21739520
http://dx.doi.org/10.1002/hed.21811
Identification of a Cut-Off for the MACIS Score to Predict the Prognosis of Differentiated Thyroid Carcinoma in Children and Young Adults. 
Head Neck, 34(5):696-701.
Jang HW, Lee JI, Kim HK, Oh YL, Choi YL, Jin DK, Kim JH, Chung JH, Kim SW. 2012.
BACKGROUND: The metastases, age at diagnosis, completeness of resection, invasion, size of the tumor (MACIS) scoring system was developed to predict disease-specific survival in patients with differentiated thyroid carcinoma (DTC), mainly for adults, with a cut-off score of 6. The purpose of this study was to evaluate its ability to predict prognosis of DTC in children and young adults. METHODS: The medical records of 66 children and young adult (<21 years old) patients with DTC were reviewed retrospectively. Receiver operating characteristic (ROC) analysis was performed to determine the cut-off for predicting poor prognosis. RESULTS: Extrathyroidal invasion and regional lymph node metastasis were noted in 64% each, and distant metastases were found in 8%. The optimal cut-off for the MACIS score for poor prognosis was 4 (93% sensitivity, 67% specificity). The overall 10-year recurrence-free survival was better in patients with MACIS score <4 than score >/=4 (p < .05). CONCLUSION: A MACIS score of more than 4 was associated with a poor prognosis in children and young adult patients with DTC.
PubMed-ID: 21748817
http://dx.doi.org/10.1002/hed.21808
Relationship Between Serum Thyroglobulin and 18FDG-PET/CT in 131I-Negative Differentiated Thyroid Carcinomas.
Head Neck, 34(5):626-31.
Giovanella L, Ceriani L, De PD, Suriano S, Castellani M, Verburg FA. 2012.
BACKGROUND: The purpose of this study was to assess the relationship between [(18) F]-fluorodeoxyglucose ((18) FDG)-positron emission tomography/CT ((18) FDG-PET/CT) and serum thyroglobulin (Tg) in patients with recurrent differentiated thyroid carcinoma (DTC). METHODS: Forty-two patients with recurrent DTC and negative Tg antibodies were included in the study. All patients underwent (131) I therapy due to an increasing serum Tg with a corresponding negative (131) I posttreatment whole body scan. The (18) FDG-PET/CT scans were then performed on all patients, serum Tg was measured concurrently, and respective results were compared. RESULTS: Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy of the (18) FDG-PET/CT examination were 93%, 84%, 93%, 84%, and 90%, respectively. The sensitivity of (18) FDG-PET/CT significantly increased in patients with serum Tg levels >/=4.6 ng/mL (96%) in comparison with patients having lower levels (25%; p < .001). Nonetheless, 3 of 27 patients (11%) with a true-positive (18) FDG-PET/CT still had a Tg <4.6 ng/mL. CONCLUSION: Although (18) FDG-PET/CT scans are more likely to be positive with pretest Tg levels >/=4.6 ng/mL, 11% of patients with DTC with a lower serum Tg level will still have a positive scan. Our findings are in contrast with the American Thyroid Association (ATA) guidelines, which only recommend to perform (18) FDG-PET/CT in patients with Tg levels >10 ng/mL.
PubMed-ID: 21850699
http://dx.doi.org/10.1002/hed.21791
Regional Recurrence After Lymphadenectomy for Clinically Evident Lymph Node Metastases From Papillary Thyroid Cancer: a Cohort Study.
Ann Surg Oncol, 19(5):1453-9.
Shah PK, Shah KK, Karakousis GC, Reinke CE, Kelz RR, Fraker DL. 2012.
BACKGROUND: The presence of lymph node (LN) metastases in papillary thyroid cancer (PTC) has limited prognostic utility for predicting disease-specific survival. Pathologic features of the LNs beyond their presence and location do not factor into the AJCC staging system. Most LN metastases are microscopic. The natural history of patients with PTC and clinically evident LN metastases (CELNM) has not been well characterized. METHODS: Patients with CELNM from PTC undergoing lymph node dissection (LND) by a single surgeon were identified (1999-2009). Patients with and without recurrence were compared by clinical and pathological factors using Student's t test, Fisher's exact test, and Chi-squared test. Logistic regression was used to determine the association between recurrence and CELNM after adjustment for confounders. RESULTS: Ninety-two patients were identified who underwent surgery for CELNM. With a median follow-up of 27.5 months, 27 patients (29%) developed regional nodal recurrence with no disease-related deaths. Patients with and without recurrence were similar with respect to all clinical and pathologic variables analyzed except for the number of metastatic LNs. With a similar number of LNs sampled in both groups, the mean number of metastatic LNs was significantly higher in the group of patients with recurrence versus those without recurrence (12 vs. 6, p = 0.03) and remained significantly associated with the likelihood of recurrence (p = 0.009) in the logistic regression model. CONCLUSIONS: Patients with CELNM have an appreciable incidence of early regional cervical recurrence but not distant metastases. Among clinical and pathological factors evaluated, the number of metastatic LNs is associated with recurrence.
PubMed-ID: 21913023
http://dx.doi.org/10.1245/s10434-011-1890-1
Patient Factors Affecting Operative Times for Single-Incision Trans-Axillary Robotic-Assisted (STAR) Thyroid Lobectomy: Does Size Matter?
Ann Surg Oncol, 19(5):1460-5.
Stevenson CE, Gardner DF, Grover AC. 2012.
BACKGROUND: Single-incision, transaxillary, robotic-assisted (STAR) thyroid lobectomy using a robotic surgical system is a novel surgical approach that is extensively described in Korean patients. Some have suggested that this experience will not translate into the American population because of differing body habitus and because the mean size of the thyroid nodules removed in Korea are <1 cm. We reviewed our experience with STAR thyroid lobectomy. METHODS: We retrospectively reviewed our prospectively collected data on consecutive cases of STAR thyroid lobectomy performed by a single surgeon. Operative times and patient outcomes were evaluated. RESULTS: Seventeen operations were performed on 15 patients. Mean total operative time was 219.3 (range, 183-256) minutes. All patients were discharged on postoperative day 1. Postoperative complications were seromas (n = 2) and cellulitis (n = 2). Operative time did not vary with the size or volume of the nodule or gland. The mean nodule diameter was 1.9 (range, 0.5-3.1) cm. The mean nodule volume and thyroid volume were 5.0 (range, 0.1-16.7) cm(3) and 20.7 (range, 11.8-45.8) cm(3), respectively. When stratified by body mass index (range, 19.6-37.8), normal versus overweight or obese, total operative time increased from 204 to 225 min, and console time from 114 to 125 min. CONCLUSIONS: STAR thyroid surgery is a feasible technique. Factors, such as mass size, specimen volume, and patient body mass index, had little effect on operative times. These differences should not hinder the adoption of this procedure in North America, because new retractor systems help to overcome them. Further evaluation of this procedure is reasonable and safe.
PubMed-ID: 21915729
http://dx.doi.org/10.1245/s10434-011-1972-0
Is One Benign Fine Needle Aspiration Enough?
Ann Surg Oncol, 19(5):1472-6.
Chernyavsky VS, Shanker BA, Davidov T, Crystal JS, Eng O, Ibrahim K, Kwong J, Trooskin SZ. 2012.
BACKGROUND: Fine needle aspiration (FNA) is used to diagnose thyroid nodules, but the follow-up of benign FNA is unclear. We sought to determine whether routine repeat FNAs after initial benign FNA reduces false negatives. METHODS: We identified 265 patients who had at least one benign FNA that either progressed to surgery or had at least one repeat FNA. We reviewed their ultrasonography, FNA cytology, and surgical pathology. RESULTS: Of 127 patients with initial benign FNA that had surgery, 13 had a malignancy, yielding a 10.2% false-negative rate. Of 22 patients who had surgery after at least two benign FNAs, one had a malignancy, yielding a 4.5% false-negative rate. Initially benign cytology (Bethesda II) was upgraded to a cytology requiring surgical intervention (Bethesda IV-VI) in 7 of 129 (5.4%) patients after two FNAs. Suspicious features on ultrasound, including size >4 cm, calcifications, or increased vascularity were found in 90% of patients with a false-negative FNA. CONCLUSIONS: The overall false-negative rate of thyroid FNAs is 10.2%, which is reduced to 4.5% with a second benign FNA. Ninety percent of patients with a false-negative FNA had suspicious sonographic features. Reaspiration should be considered in patients with sonographically suspicious nodules.
PubMed-ID: 21969084
http://dx.doi.org/10.1245/s10434-011-2079-3
Clinical Efficacy of Sentinel Lymph Node Biopsy Using Methylene Blue Dye in Clinically Node-Negative Papillary Thyroid Carcinoma.
Ann Surg Oncol, 19(6):1868-73.
Ji YB, Lee KJ, Park YS, Hong SM, Paik SS, Tae K. 2012.
BACKGROUND: Sentinel lymph node biopsy (SLNB) has recently been used to detect occult lymph node metastases. The aim of this study was to assess the feasibility and clinical efficacy of SLNB in the treatment of clinically node-negative papillary thyroid carcinoma. METHODS: A total of 114 consecutive patients with clinically node-negative papillary thyroid carcinoma were enrolled and underwent SLNB. After injection of 1% methylene blue around the tumors, blue-stained sentinel lymph nodes (SLN) were collected from the central compartments. All the patients underwent total thyroidectomy with bilateral central compartment neck dissection after SLNB. RESULTS: SLN were identified in 84 (73.7%) of the 114 patients. Of these 84 patients, 24 (28.6%) had metastases in the SLN. Among the 60 patients who had no metastases in their SLN in frozen biopsy samples, seven had metastatic foci in their SLN in the permanent biopsy samples and six had metastases in their non-SLN samples. Central compartment lymph node metastases were detected in 11 of the 30 patients in whom SLN were not identified. Thus, the sensitivity, specificity, and positive and negative predictive values of SLNB were 64.9, 100, 100, and 78.3%, respectively. The false-positive and false-negative rates were 0 and 35.1%, respectively. The detection of SLN led to no major complications. CONCLUSIONS: SLNB using methylene blue in papillary thyroid carcinoma is a safe and technically feasible procedure. However, it is of limited use in the management of clinically node-negative papillary thyroid carcinoma because of low sensitivity and a high false-negative rate.
PubMed-ID: 21989668
http://dx.doi.org/10.1245/s10434-011-2109-1
The Role of Preoperative Neck Ultrasounds to Assess Lymph Nodes in Patients With Suspicious or Indeterminate Thyroid Nodules.
J Surg Oncol, 105(6):601-5.
Roy R, Kouniavsky G, Venkat R, Felger EA, Shiue Z, Schneider E, Zeiger MA. 2012.
BACKGROUND AND OBJECTIVES: Currently there are no recommendations for obtaining a preoperative neck ultrasound for patients with suspicious or indeterminate thyroid nodules. Because a preoperative surgical ultrasound can detect suspicious lymph nodes that could result in ultimately altering surgical management, we chose to study which variables were predictive of this change. METHODS: Medical records of 173 patients who presented between January 2006 and December 2010 with suspicious or indeterminate thyroid cytology were retrospectively reviewed. Clinicopathological variables were analyzed to determine factors predictive of malignancy and a change in operative approach. RESULTS: One hundred thirty-four of 173 patients were evaluable. Seventeen of 134 (12.6%) of the preoperative ultrasounds were suspicious. Seven of 134 (5.2%) patients underwent a formal lymph node dissection based on ultrasound findings. Size of tumor, Bethesda FNAB category, and male gender were associated with malignancy while thyroid nodule microcalcifications and category of FNAB were associated with performing lymph node dissections. CONCLUSION: Thyroid nodule microcalcifications on ultrasound and category of FNAB appear to be the best predictors of metastatic disease. Because the surgical approach was altered in only a few patients, further analysis is needed to delineate whether performing cervical ultrasound for suspicious/indeterminate nodules is cost effective.
PubMed-ID: 22006435
http://dx.doi.org/10.1002/jso.22115
Aggressive Variants of Papillary Thyroid Cancer: Incidence, Characteristics and Predictors of Survival Among 43,738 Patients.
Ann Surg Oncol, 19(6):1874-80.
Kazaure HS, Roman SA, Sosa JA. 2012.
BACKGROUND: The diffuse sclerosing (DSV) and tall cell (TCV) variants are considered aggressive subtypes of papillary thyroid cancer (PTC) for which data are limited. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (1988-2008) was used to compare the incidence and clinical/pathologic characteristics of DSV and TCV with classic PTC. Prognostic factors associated with survival were analyzed by chi-square test, analysis of variance, log rank test, and Cox multivariate regression. RESULTS: There were 261 DSV, 573 TCV, and 42,904 PTC patients. Compared to a 60.8% increase in classic PTC incidence, DSV and TCV incidence increased by 126% (P (trend) = 0.052) and 158% (P (trend) = 0.002), respectively. Aggressive variants were associated with higher rates of extrathyroidal extension, multifocality, and nodal and distant metastasis (all P < 0.001) compared to classic PTC. Nodal metastasis was more likely with DSV (72.2% vs. 66.8% TCV vs. 56.3% PTC, P < 0.001); distant metastasis was most common with TCV (11.1% vs. 7.3% DSV vs. 4.3% PTC, P < 0.001). After adjustment, DSV [hazard ratio (HR) 1.8, P = 0.007] and TCV (HR 1.9, P < 0.001) histologies were associated with significantly reduced survival (5-year overall: 87.5% DSV, 80.6% TCV vs. 93.5% PTC, P < 0.001). Tumor size independently predicted worse prognosis for TCV (HR 1.29, P < 0.001) but not DSV patients. Thyroid surgery and radioiodine improved survival of DSV and TCV patients (all P < 0.05). Patients with aggressive variants who received external-beam radiotherapy did not experience improved survival. CONCLUSIONS: DSV and TCV are rare, increasing in incidence, and have a worse prognosis than classic PTC. Patients with these variants should be treated aggressively with thyroidectomy and radioiodine, regardless of tumor size.
PubMed-ID: 22065195
http://dx.doi.org/10.1245/s10434-011-2129-x
Serum Thyrotropin As a Risk Factor for Thyroid Malignancy in Euthyroid Subjects With Thyroid Micronodule.
Head Neck, 34(7):949-52.
Moon SS, Lee YS, Lee IK, Kim JG. 2012.
BACKGROUND: An elevated thyroid stimulating hormone (TSH) level is a risk factor for differentiated thyroid cancer. The present study investigated whether TSH is a risk factor for thyroid microcarcinoma (TMC) in euthyroid subjects with a micronodule. METHODS: In this cross-sectional study, 483 euthyroid subjects (77 males patients, 406 females patients) with a thyroid micronodule were enrolled and underwent ultrasound guided fine-needle aspiration biopsy. Serum TSH level was measured in every subject. The final diagnostic outcome (malignant or benign) was defined in conjunction with cytology and histology. RESULTS: Compared with the patients below the population mean, patients above the population mean had a significantly higher malignancy rate (10.8% vs 4.8%, p = .025). Multiple logistic regression analysis revealed TSH as an independent risk factor for malignancy in euthyroid patients with a micronodule (odds ratio, 1.449; 95% confidence interval, 1.033-2.033; p = .031). CONCLUSIONS: Measurement of TSH in subjects with a thyroid micronodule is helpful to estimate cancer risk.
PubMed-ID: 22127951
http://dx.doi.org/10.1002/hed.21828
Intraoperative Stimulation Neuromonitoring Versus Intraoperative Continuous Electromyographic Neuromonitoring in Total Thyroidectomy: Identifying Laryngeal Complications.
Am J Surg, 204(1):49-53.
Koulouris C, Papavramidis TS, Pliakos I, Michalopoulos N, Polyzonis M, Sapalidis K, Kesisoglou I, Gkoutzamanis G, Papavramidis ST. 2012.
BACKGROUND: Laryngeal complications occur in thyroidectomies as a result of several factors, but especially because of nerve damage. We compared intraoperative stimulation neuromonitoring (IONM) with intraoperative continuous electromyographic neuromonitoring (IEM) to evaluate their ability to identify postoperative laryngeal complications. METHODS: This prospective clinical trial included 174 patients (348 nerves) who had both IONM and IEM. We recorded age, sex, pathology, vocal fold motility, and complications. RESULTS: IONM identified 334 nerves, whereas IEM identified 348. Five patients had transient laryngeal complications, 2 bilateral, and 3 unilateral recurrent laryngeal nerve paresis. In addition, in 2 patients IEM showed placement of the tracheal tube balloon on the vocal folds, which led to correction. Sensitivity and specificity were 96.48% and 100% for IONM and 100% and 100% for IEM, respectively. IONM had a positive predictive value of 100% and a negative predictive value of 36.84%. The positive and negative predictive values of IEM were 100%. CONCLUSIONS: Both techniques identify recurrent laryngeal nerve injuries; however, IEM seems to have an advantage concerning the nonsurgical laryngeal complications and may play a role in preventing morbidity.
PubMed-ID: 22169175
http://dx.doi.org/10.1016/j.amjsurg.2011.05.011
Functional Voice and Swallowing Outcomes After Robotic Thyroidectomy by a Gasless Unilateral Axillo-Breast Approach: Comparison With Open Thyroidectomy.
Surg Endosc, 26(7):1871-7.
Tae K, Kim KY, Yun BR, Ji YB, Park CW, Kim DS, Kim TW. 2012.
BACKGROUND: Voice and swallowing alterations are common complaints after thyroidectomy, even in the absence of laryngeal nerve impairment. However, voice and swallowing functions after robotic thyroidectomy have not been thoroughly investigated. This study compared the functional outcomes for voice and swallowing after robotic thyroidectomy and conventional open thyroidectomy. METHODS: The study prospectively analyzed the voice and swallowing functions of patients with thyroid nodules who underwent robotic thyroidectomy by a gasless unilateral axillo-breast (GUAB) approach (50 cases) or by conventional open thyroidectomy (61 cases) from September 2009 to October 2010. Videolaryngostroboscopy or flexible laryngoscopy was performed pre- and postoperatively. Subjective voice and swallowing alterations were assessed by questionnaire preoperatively and then 1 day, 1 week, 1 month, 3 months, and 6 months postoperatively. In addition, objective acoustic voice analysis was performed using a Multidimensional Voice Program, with Voice Range Profiles and maximum phonation times measured preoperatively and then 1 week, 1 month, 3 months, and 6 months postoperatively. RESULTS: Subjective postoperative voice function was significantly better in the robotic group at 1 day, 1 month, and 3 months postoperatively than in the open group. The mean values of fundamental frequency, jitter, shimmer and noise-to-harmonic ratio before and after surgery did not differ between the two groups. However, the frequency range and the highest frequency were significantly better in the robotic group than in the open group at 3 months postoperatively. Subjective swallowing function did not differ between the two groups. CONCLUSION: Postoperative voice function is better with robotic thyroidectomy using the GUAB approach than with conventional open thyroidectomy. This is an advantage of robotic thyroidectomy by the GUAB approach in addition to the excellent cosmesis.
PubMed-ID: 22205465
http://dx.doi.org/10.1007/s00464-011-2116-0
Risk of Subsequent Primary Thyroid Cancer After Another Malignancy: Latency Trends in a Population-Based Study.
Ann Surg Oncol, 19(6):1887-96.
Lal G, Groff M, Howe JR, Weigel RJ, Sugg SL, Lynch CF. 2012.
PURPOSE: To evaluate the risk of a subsequent primary thyroid cancer (SPTC) in patients with common invasive cancers, with attention to latency trends and histology associations. METHODS: Patients with one of 10 common invasive cancers were followed from 1975 to 2008 in 9 registries participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Standardized incidence ratios (SIRs) for SPTC were determined by the multiple primary-SIR program in SEER*Stat. RESULTS: A total of 2502 SPTCs were observed. Greatly elevated SIRs for SPTC were noted for 9 of 10 evaluated cancers in the 12 months after initial diagnosis. The SIRs remained elevated 12-59 months after diagnosis for all cancers except leukemia, uterine, and bladder cancers. Increased risks persisted 60-119 months beyond diagnosis for renal (SIR 2.56) and breast cancer (SIR 1.16); and 120+ months for renal cancer (SIR 2.46). Increased SPTC risk after renal and female breast cancers was mostly seen in nonirradiated patients. The principal histology association was between papillary thyroid cancer and renal cell carcinomas. CONCLUSIONS: Many common cancers are associated with increased risk of SPTC beyond 12 months of initial diagnosis. Although this can be explained partly by continued surveillance bias, radiation effects, and known rare familial associations for some tumors, these factors alone are unlikely to explain the persistent, significant two-way association with renal and breast cancers. Additional research is needed to further define the biological and environmental mechanisms underlying these associations.
PubMed-ID: 22227921
http://dx.doi.org/10.1245/s10434-011-2193-2
Clinical Implication of Elastography As a Prognostic Factor of Papillary Thyroid Microcarcinoma.
Ann Surg Oncol, 19(7):2279-87.
Moon HJ, Kim EK, Yoon JH, Kwak JY. 2012.
BACKGROUND: A firm and hard thyroid nodule on palpation is known to be associated with an increased risk of thyroid malignancy. Elastography has been introduced to evaluate the tissue hardness objectively. We investigated the clinical implications of elastography as a prognostic factor in patients with papillary thyroid microcarcinoma. METHODS: Elastography images were classified according to Rago scores of 1-5. Malignancies with Rago scores of 4 or 5 were considered as "hard" and remaining malignancies as "soft." Clinicopathologic characteristics were compared between patients with hard or soft malignancies according to the extrathyroidal extension and central and lateral lymph node metastasis by using chi-square tests, Fisher's exact test, and independent t tests. Odds ratios with 95% confidence intervals were calculated for evaluating the factors for predicting extrathyroidal extension and central and lateral lymph node metastasis. RESULTS: A hard malignancy on the Rago score was significantly associated with pathologic extrathyroidal extension compared with a soft malignancy (P=0.001). The odds ratio of a hard malignancy on the Rago score for predicting extrathyroidal extension was 5.060 (95% confidence interval, 1.565-16.358). A hard malignancy on Rago scores was not associated with central or lateral lymph node metastasis. CONCLUSIONS: A hard malignancy on the Rago score of elastography was an independent factor for predicting pathologic extrathyroidal extension on pathology.
PubMed-ID: 22246427
http://dx.doi.org/10.1245/s10434-011-2212-3
Prognostic Factors for Recurrence of Papillary Thyroid Carcinoma in the Lymph Nodes, Lung, and Bone: Analysis of 5,768 Patients With Average 10-Year Follow-Up.
World J Surg, 36(6):1274-8.
Ito Y, Kudo T, Kobayashi K, Miya A, Ichihara K, Miyauchi A. 2012.
BACKGROUND: Papillary thyroid carcinoma (PTC) frequently recurs to the lymph nodes, which may not be fatal immediately but is a stressor for physicians and patients. Recurrence to the distant organs, although less frequent, is often life-threatening, and the lung and bone are organs to which PTC is likely to recur. In the present study we investigated factors predicting recurrence of PTC to the lymph nodes, lung, and bone in a large number of patients undergoing long-term follow-up. METHODS: A total of 5,768 PTC patients (608 males and 5,159 females) without distant metastasis at diagnosis who underwent initial surgery between 1987 and 2004 in Kuma Hospital were enrolled in this study. The postoperative follow-up ranged from 12 to 280 months, and was 129 months (10.8 years) on average. RESULTS: To date, node, lung, and bone recurrences have been detected in 389 (7%), 118 (2%), and 33 patients (0.6%), respectively, and 57 patients (1%) have died of PTC. We examined the prognostic significance of the tumor size (T), extrathyroid extension (Ex), age 55 years or older (Age), male gender (Gender), clinical node metastasis (N), and extranodal tumor extension (LN-Ex) for each outcome on multivariate analysis. Age, Gender, T > 2 cm, N, and Ex were independent predictors of lymph node recurrence. Age, Ex, T > 2 cm, and N were independent prognostic factors for lung recurrence. Ex, T > 4 cm, and N independently predicted bone recurrence. Of these, N >/= 3 cm had the strongest prognostic value for lymph node, lung, and bone recurrences. In contrast, Age was the strongest predictor for carcinoma death. LN-Ex also had a prognostic value for carcinoma death, although it was not a predictor of carcinoma recurrence. Ex, N >/= 3 cm, and T > 2 cm also had a prognostic impact on carcinoma death. CONCLUSIONS: Large lymph node metastasis showed a strong prognostic impact on carcinoma recurrence not only to the lymph nodes but also to the lung and bone, and carcinoma death. Extrathyroid extension also independently predicted these recurrences and carcinoma death, although hazard ratios were lower than for large node metastasis. Age 55 years or older, in contrast, was the strongest predictor of carcinoma death. Extranodal tumor extension did not independently affect recurrence, but it had prognostic significance for carcinoma death. These findings suggest that recurring PTC lesions of older patients and/or extranodal tumor extensions are difficult to control and very progressive.
PubMed-ID: 22270990
http://dx.doi.org/10.1007/s00268-012-1423-5
Not the Number but the Location of Lymph Nodes Matters for Recurrence Rate and Disease-Free Survival in Patients With Differentiated Thyroid Cancer.
World J Surg, 36(6):1262-7.
de Meer SG, Dauwan M, de KB, Valk GD, Borel Rinkes IH, Vriens MR. 2012.
BACKGROUND: Several Japanese studies have focused on identifying prognostic factors in patients with positive lymph nodes to predict recurrence rate and disease-free survival (DFS). However, different treatment protocol is followed in Japan compared with the European and American approach. This study was designed to investigate whether the number and/or location of lymph nodes predicts prognosis in patients with DTC treated with total thyroidectomy, lymph node dissection, and postoperative radioactive iodine ablation. METHODS: All 402 patients who were treated at the Department of Nuclear Medicine between 1998 and 2010 for DTC were reviewed. Patients were treated with (near) total thyroidectomy, lymph node dissection on indication, and postoperative I-131 ablation. Median follow-up was 49 (range, 10-240) months. Outcome measures were recurrence rate, disease-free survival, and mean time to recurrence. RESULTS: Ninety-seven patients had proven lymph node metastases. Recurrence rate was significantly higher in patients with positive lymph nodes in the lateral compartment vs. patients with lymph node metastasis in the central compartment (60 vs. 30%, p = 0.007). Disease-free survival and mean time to recurrence also were significantly shorter (30 vs. 52 months, p = 0.035 and 7 vs. 44 months, p = 0.004, respectively). The number of lymph nodes and extranodal growth were not significantly associated with the outcome measures used. CONCLUSIONS: The location of positive lymph nodes was significantly correlated with the risk of recurrence and a shorter DFS. Hence, the TNM criteria are useful in subdividing patients based on risk of recurrence and DFS.
PubMed-ID: 22270993
http://dx.doi.org/10.1007/s00268-012-1427-1
Evaluation of Postoperative Radioactive Iodine Scans in Patients Who Underwent Prophylactic Central Lymph Node Dissection.
World J Surg, 36(6):1268-73.
Laird AM, Gauger PG, Miller BS, Doherty GM. 2012.
BACKGROUND: Prophylactic central lymph node dissection (CLND) accompanying total thyroidectomy for papillary thyroid cancer (PTC) remains controversial. Our hypothesis is that CLND may help select patients who benefit from postoperative radioactive iodine (RAI). METHODS: A total of 119 patients who were clinically node-negative underwent total thyroidectomy/bilateral CLND for papillary thyroid cancer (PTC) > 1 cm during 2002-2010. Pathology results, RAI results, and outcomes were compared between node-positive (NP) and node-negative (NN) patients. RESULTS: NP and NN patients were similar in age, gender, tumor size, and MACIS score. Median number of nodes excised was six. The rate of permanent hypocalcemia was 1.7% without permanent recurrent laryngeal nerve injuries. Thirteen of 52 (25%) NN patients and 24 of 67 (36%) NP patients had suspicious nodes by intraoperative inspection. The node assessment negative predictive value was 75%; positive predictive value was 36%. Fifty-six percent (67/118) were NP; 100 patients were treated with RAI. Fourteen of 62 NP patients had abnormal postoperative RAI scans aside from the thyroid remnant versus 4 of 38 NN patients (23 vs. 11%, p = 0.18). Median 1-year stimulated thyroglobulin (Tg) level was 0.0 for both (range 0.0-1.2, NN; 0.0-22.7, NP; p = 0.1). NP patients received higher doses of RAI (150 vs. 30 mCi, p < 0.001). Rate of recurrent or persistent disease was 3.4%. CONCLUSIONS: Few node-negative patients have abnormal RAI scans outside of the thyroid bed. Node-positive patients had greater variability in stimulated 1-year Tg levels after higher doses of RAI. CLND may identify the patients most likely to have persistently elevated stimulated Tg after initial therapy for PTC.
PubMed-ID: 22270997
http://dx.doi.org/10.1007/s00268-012-1431-5
[Current TNM System of the UICC/AJCC : the Prognostic Significance for Differentiated Thyroid Carcinoma]
Aktuelles TNM-System Der UICC/AJCC : Prognostische Bedeutung Beim Differenzierten Schilddrusenkarzinom.
Chirurg, 83(7):646-51.
Stratmann M, Sekulla C, Dralle H, Brauckhoff M. 2012.
BACKGROUND: The aim of study was an evaluation of prognostic factors of the current TNM version (UICC/AJCC 2009, 7th revision) for differentiated thyroid carcinoma (DTC). PATIENTS AND METHODS: A total of 368 patients with DTC (papillary thyroid carcinoma [PTC] n = 269, follicular thyroid carcinoma [FTC] n = 99) were included. Disease-specific survival (DSS) was calculated based on the different TNM stages (mean follow-up 60 +/- 37.5 months). RESULTS: When compared to patients with FTC, PTC patients had smaller tumors (diameter 19 mm versus 33 mm), more often lymph node metastases (40.9% versus 9.1%) but less frequent distant metastases (2.6 versus 13.1%) and poorly differentiated variants (PDTC 3.0% versus 8.1%). The 5-year and 10-year DSS for PTC versus FTC were 97.3% versus 91.5% and 96.2% versus 91.5% (p = 0.086), respectively. When comparing different TNM categories between well-differentiated PTC and FTC, no statistically significant differences were found but PDTCs, had a significantly worse DSS. CONCLUSIONS: The current TNM system is a sufficient tool for predicting DSS in well-differentiated PTC. In FTC, the extent of capsular and vascular invasion should also be considered. The implementation of a specific TNM system for PDTC needs to be confirmed in further studies.
PubMed-ID: 22273853
http://dx.doi.org/10.1007/s00104-011-2216-3
Reoperative Surgery for Bilateral Multinodular Goitre in the Era of Total Thyroidectomy.
Br J Surg, 99(5):688-92.
Vasica G, O'Neill CJ, Sidhu SB, Sywak MS, Reeve TS, Delbridge LW. 2012.
BACKGROUND: Total thyroidectomy, rather than bilateral subtotal thyroidectomy, is now accepted as the preferred management for bilateral benign multinodular goitre (BMNG) in order to reduce the need for reoperative surgery. The aim of this study was to examine whether this approach has had an impact on presentation for bilateral reoperative thyroid surgery. METHODS: This was a retrospective cohort study. The study group comprised patients presenting with recurrent BMNG who underwent bilateral reoperative thyroid surgery following previous bilateral subtotal or partial thyroidectomy. They were compared with patients undergoing unilateral reoperative thyroid surgery following previous lobectomy, and those undergoing primary total thyroidectomy for BMNG. RESULTS: Between 1 January 1987 and 31 December 2009, 12 354 consecutive thyroid procedures were undertaken. Among those with BMNG, primary total thyroidectomy was undertaken in 3298 patients, unilateral reoperative thyroidectomy in 337 and bilateral reoperative thyroidectomy in 191. Presentations of patients with recurrent BMNG declined gradually over the study period following the change in policy from subtotal to total thyroidectomy; only five patients (representing less than 0.5 per cent of all thyroid surgery) underwent bilateral reoperative surgery for BMNG in the last year of the study. Four of these patients had their initial operation before 1987 and in another unit, whereas the remaining patient initially had surgery overseas. CONCLUSION: The introduction of a policy of initial total thyroidectomy for bilateral BMNG has essentially eliminated the need for bilateral reoperative surgery for recurrent goitre.
PubMed-ID: 22287186
http://dx.doi.org/10.1002/bjs.8684
Video-Assisted Versus Conventional Total Thyroidectomy and Central Compartment Neck Dissection for Papillary Thyroid Carcinoma.
World J Surg, 36(6):1225-30.
Lombardi CP, Raffaelli M, De CC, Sessa L, Rampulla V, Bellantone R. 2012.
BACKGROUND: Although video-assisted (VA) thyroidectomy emerged as effective treatment for selected patients with papillary thyroid carcinoma (PTC), some concerns remain about obtaining adequate central neck node clearance. We compared patients who underwent VA and conventional total thyroidectomy (TT) and central compartment dissection (CCD) for PTC. METHODS: A total of 52 consecutive patients successfully underwent VA-TT and VA-CCD for PTC (VA group) were compared to 52 controls who underwent conventional TT and CCD (C group) for PTC. RESULTS: The two groups were matched for age (p = 0.75), sex (p = 0.07), and tumor size (p = 1.0). Operating time (p = 0.23), overall postoperative complications (p = 0.41), pT (p = 0.44), and pN (p = 0.84) were similar in the two groups. The mean number of removed nodes was similar (10.6 +/- 4.6 in VA group vs. 12.2 +/- 5.6 in C group) (p = 0.11).Mean postoperative serum thyroglobulin (sTg) off levothyroxine (LT4) suppressive treatment was 3.2 +/- 5.0 ng/ ml in the VA group and 2.6 +/- 7.4 ng/ml in the C-group (P = 0.67). Mean postoperative radioiodine uptake (RAIU) was similar in the two groups (1.5 +/- 1.3 vs. 1.7 +/- 1.3%) (p = 0.49). When pN1a patients alone were considered, no difference was found between the VA group (21 patients) and the controls (24 patients) concerning the mean number of removed nodes (10.3 +/- 4.1 vs. 12.4 +/- 5.6) (p = 0.16), the mean sTg off LT4 (4.4 +/- 6.0 vs. 1.9 +/- 2.7 ng/ml) (p = 0.07) and the mean RAIU (1.9 +/- 1.5 vs. 1.7% +/- 1.3%) (p = 0.63). CONCLUSIONS: The results of VA-TT and CCD in selected cases of PTC appear to be comparable to those of conventional surgery. A longer follow-up and larger series are necessary to draw definitive conclusions concerning longterm outcomes.
PubMed-ID: 22302283
http://dx.doi.org/10.1007/s00268-012-1439-x
Prognostic Factors and Treatment Outcomes for Anaplastic Thyroid Carcinoma: ATC Research Consortium of Japan Cohort Study of 677 Patients. 
World J Surg, 36(6):1247-54.
Sugitani I, Miyauchi A, Sugino K, Okamoto T, Yoshida A, Suzuki S. 2012.
BACKGROUND: Anaplastic thyroid carcinoma (ATC) accounts for only 1 to 2% of all thyroid carcinomas, but it is one of the most lethal neoplasms in humans. To date, most findings about ATC have been derived from single-institution studies with limited numbers of cohorts. To obtain further insights into this "orphan disease," we have established a multicenter registry, the ATC Research Consortium of Japan (ATCCJ). We analyzed prognostic factors and treatment outcomes using the large cohort database of the ATCCJ. METHODS: Most of the Japanese centers involved in the treatment of thyroid cancer were invited to join the ATCCJ and have provided information on ATC patients treated between 1995 and 2008. The database includes 677 cases from 38 registered institutions. Survival curves were determined using Kaplan-Meier methods and were compared using the log-rank test. Cox's proportional hazards model was used for multivariate analysis. RESULTS: Clinical varieties of ATC were classified into four types: common type (n = 547); incidental type (n = 29); anaplastic transformation at the neck (n = 95); anaplastic transformation at a distant site (n = 6). The incidental type followed by anaplastic transformation at the neck showed better outcomes than the other types. Anaplastic transformation at a distant site showed the worst outcomes. The 6-month and 1-year cause-specific survival (CSS) rates for common-type ATC were 36 and 18%, respectively. In all, 84 (15%) achieved long-term (>1 year) survival. Multivariate analysis identified age >/=70 years, presence of acute symptoms, leukocytosis (white blood cell count >/=10,000/mm(3)), large tumor >5 cm, T4b tumor, and distant metastasis as significant risk factors for lower survival. CSS rates also differed significantly depending on UICC stages, with 6-month CSSs of 60% for stage IVA, 45% for IVB, and 19% for IVC. For 36 of 69 (52%) stage IVA patients who underwent radical surgery, adjuvant therapies, including radiation therapy (RTX) and chemotherapy (CTX) did not show additional benefit statistically. Conversely, among 242 stage IVB patients, 80 (33%) underwent radical surgery. For those patients, therapies combining RTX with CTX significantly improved CSS. CONCLUSIONS: Long-term survival is possible for selected patients with ATC. To determine the treatment strategy, UICC stage (disease extent) and other prognostic factors (e.g., biologic malignancy grade) should be considered.
PubMed-ID: 22311136
http://dx.doi.org/10.1007/s00268-012-1437-z
Robotic Transaxillary Endocrine Surgery: a Comparison With Conventional Open Technique.
Surg Endosc, 26(8):2259-66.
Foley CS, Agcaoglu O, Siperstein AE, Berber E. 2012.
BACKGROUND: Robotic transaxillary (RT) endocrine surgery may improve cosmetic outcomes. We report our initial experience in RT thyroid and parathyroid surgery and the associated learning curve, and compare early surgical outcomes to those of open thyroidectomy (OT) and focal parathyroidectomy (FP). METHODS: A prospective database review identified patients who had undergone RT endocrine surgery. A case-matched group who underwent OT or FP was also identified. Demographics, histopathology, operative outcomes, and follow-up data were collected. Groups were compared using Student's t test and the chi(2) test. RESULTS: Fifteen RT procedures were performed: 11 RT thyroidectomies (6 total, 5 lobectomies) and 4 RT parathyroidectomies (2 focal, 2 unilateral), representing 5.9% and 2.2% of thyroidectomies and parathyroidectomies performed. The OT group contained 16 patients (13 totals, 3 lobectomies). The FP group contained 12 patients. There was no significant difference in age, gender, BMI, pathology, or complications between the groups. Mean operating time was significantly longer in the RT group (232 vs. 109 min, P = 0.0002) as was mean incision length (6 vs. 3.6 cm, P < 0.0001). No RT procedures were converted and no major complications occurred. Operating time decreased significantly over consecutive cases demonstrating a learning curve. CONCLUSIONS: RT thyroidectomy and parathyroidectomy can be performed safely by specialist endocrine surgeons, early in their learning curve, without an increased complication rate, albeit with significantly longer operating times.
PubMed-ID: 22311302
http://dx.doi.org/10.1007/s00464-012-2169-8
Disparity in the Management of Graves' Disease Observed at an Urban County Hospital: a Decade-Long Experience.
Am J Surg, 204(2):199-202.
Jin J, Sandoval V, Lawless ME, Sehgal AR, McHenry CR. 2012.
BACKGROUND: The objective of this study was to determine whether health care disparities exist in management of Graves' disease. METHODS: Patients treated for Graves' disease from 1999 to 2009 were divided into medical and surgical treatment groups. A comparative analysis of age, sex, race, health insurance, and income was completed. Address and/or zip code were geocoded and median income was determined from census data. RESULTS: A total of 634 patients were treated for Graves' disease; 535 (84%) medically and 99 (16%) surgically. Mean age (40 +/- 15 vs 43 +/- 11 y), percentage of women (84% vs 91%), and racial distribution were similar in the 2 groups (P > .05). In the surgical group, median income was lower ($31,530 vs $34,404; P = .07) and 52% of patients were uninsured compared with 30% of patients treated medically (P < .0001). CONCLUSIONS: A disproportionate number of uninsured patients underwent thyroidectomy for Graves' disease. Social and economic factors may have a role in determining definitive therapy for Graves' disease.
PubMed-ID: 22317948
http://dx.doi.org/10.1016/j.amjsurg.2011.10.010
Impact on Overall Survival of Radioactive Iodine in Low-Risk Differentiated Thyroid Cancer Patients.
J Clin Endocrinol Metab, 97(5):1526-35.
Schvartz C, Bonnetain F, Dabakuyo S, Gauthier M, Cueff A, Fieffe S, Pochart JM, Cochet I, Crevisy E, Dalac A, Papathanassiou D, Toubeau M. 2012.
CONTEXT: American Thyroid Association and European Thyroid Association guidelines cannot recommend for or against radioactive iodine (RAI) ablation after surgery in low-risk differentiated thyroid cancer (DTC) patients. OBJECTIVES: The objective of the study was to assess the survival benefit of RAI for these patients. DESIGN: We identified 1298 DTC patients at low risk treated between 1975 and 2005. Logistic regressions were used to identify variables associated to RAI and to calculate the propensity score to receive RAI after surgery. We compared overall survival (OS) and disease-free survival (DFS) according to RAI with the log-rank tests and univariate and multivariate Cox analyses. Analyses stratified on propensity score were also performed. RESULTS: Median follow-up was 10.3 yr. Nine hundred eleven patients received RAI after surgery vs. 387 patients without RAI after surgery. Using univariate analysis, 10-yr OS was found to be 95.8% in patients without RAI after surgery vs. 94.6% in RAI after surgery (P = 0.006), and 10-yr DFS was found to be 93.1% vs. 88.7% (P = 0.001). All clinical factors except sex were significantly associated with RAI. Using multivariate Cox analyses, RAI was neither significantly nor independently associated with OS (P = 0.243) and DFS (P = 0.2659). After stratification on propensity score, Cox univariate analyses showed that OS did not differ according to RAI (P = 0.3524), with a hazard ratio for RAI of 0.75 (95% confidence interval 0.40-1.38). Similarly, DFS did not differ (P = 0.48) with a stratified univariate hazard ratio of 1.11 (95% confidence interval 0.73-1.70). CONCLUSION: With a long-term follow-up of 10.3 yr, we failed to prove any survival benefit of RAI after surgery in a large cohort of low-risk DTC patients.
PubMed-ID: 22344193
http://dx.doi.org/10.1210/jc.2011-2512
Prognostic Factors in Differentiated Thyroid Cancer--a 20-Year Surgical Outcome Study.
Langenbecks Arch Surg, 397(5):809-15.
Konturek A, Barczynski M, Nowak W, Richter P. 2012.
AIMS: The aim of this study was to determine prognostic factors in patients operated on for well-differentiated thyroid cancer (WDTC). PATIENTS AND METHODS: A retrospective cohort study of patients with WDTC treated at our institution between 1989 and 1991 (n = 97; mean age 52.3 years, 78 females, follow-up 124.6 +/- 75.1 months) was made. Multivariate analysis was performed including: age, gender, size of primary tumor, location and number of foci in thyroid tissue, clinical stage, thyroid capsule infiltration, tumor histological type, extent of surgery, prognosis based on the AGES and MACIS scores, and tumor proliferative activity based on determination of proliferating cell nuclear antigen (PCNA) and Ki-67 expression in tumor tissue and nodal metastases. RESULTS: The multivariate analysis showed increased relative risk (RR) of death for: age above 60 years (7.39; p < 0.001), pTm (2.94; p = 0.002), pT3 (11.83; p < 0.001), and pN1 (4.11; p < 0.001). Total thyroidectomy decreased RR of death (0.39; p = 0.023) when compared to more limited resections. Moderate and high PCNA index was associated with 48.3% and 87.5% mortality, respectively, while Ki-67 index was associated with the highest mortality rate (76%) in the group of medium values. CONCLUSIONS: Despite good prognosis in WDTC, factors that most significantly affect overall survival rate include age, size of primary lesion and multifocal disease, presence of nodal metastases, and extent of primary surgery.
PubMed-ID: 22350610
http://dx.doi.org/10.1007/s00423-011-0899-z
Robotic Facelift Thyroidectomy: Facilitating Remote Access Surgery.
Head Neck, 34(5):746-7.
Terris DJ, Singer MC. 2012.
BACKGROUND: A novel remote access robotic thyroidectomy technique has been described that uses as its portal a postauricular and occipital hairline (facelift) incision. Experimental investigation and clinical validation have been completed. A detailed technical description is provided. METHODS AND MATERIALS: A young woman with a thyroid nodule was referred for surgery. Because of her concerns about a visible neck scar, she opted for remote access thyroidectomy. RESULTS: A left robotic facelift thyroidectomy was performed in less than 2 hours as a drainless, outpatient procedure. Videographic demonstration of the robotic resection is included. CONCLUSIONS: A number of remote access thyroidectomy techniques have proliferated. We developed and described an intuitive approach that uses familiar dissection planes and avoids the need for breast incisions and crossing the clavicle.
PubMed-ID: 22362411
http://dx.doi.org/10.1002/hed.22978
Heat Production, Nerve Function, and Morphology Following Nerve Close Dissection With Surgical Instruments.
World J Surg, 36(6):1361-7.
Carlander J, Koch C, Brudin L, Nordborg C, Gimm O, Johansson K. 2012.
BACKGROUND: The aim of the present study was to compare an ultrasonically activated instrument (US), monopolar electrosurgery, and bipolar electrosurgery (ES) with respect to heat production, nerve function, and nerve morphology following in vivo application. MATERIALS AND METHODS: The biceps femoris muscle of anesthetized rats was cut in a standardized manner longitudinally 1 mm adjacent to the sciatic nerve using US shears, a monopolar ES knife, or a bipolar ES scissors. Activation time and temperature were recorded continuously within 1-4 mm of the activation site ipsilateral and contralateral to the nerve with two thermoelectric microsensors. Temperature rise and time delay of reaching the temperature maximum, as an expression of heat spread within tissue, maximum temperature, and thermal dose (equivalent time of exposure at 43 degrees C) were measured and calculated. A total of 49 functional experiments were conducted. The electromyographic (EMG) potential was recorded distally. Nerve dysfunction was defined as more than 10% loss of the evoked EMG amplitude. Forty-eight nerves were coded and submitted to blind histopathological examination, and morphological damage was graded on a 4-grade scale. RESULTS: The maximum temperature elevation and the thermal dose were significantly higher for the bipolar ES compared with the US instrument (p = 0.024, p = 0.049), and with much less variation of results for the US instrument. The monopolar ES maximum temperature and thermal dose were lower, but a very large variation occurred, probably as a result of more random electrical spread to the ground electrode and muscle motion artifacts. Functional loss was least common in the US group-without being significant-compared to bipolar and monopolar ES. Moderate and severe morphological damage was significantly less common in the US group than in the monopolar ES group (p = 0.041). We found no statistically significant correlation between the highest temperatures and the degree of morphological damage or functional loss. CONCLUSIONS: The temperature elevation depends strongly on the distance to the activated instrument. The bipolar ES scissors generates a higher maximum temperature and thermal dose with a greater variation in than the US. Functional loss and severe morphological damage were uncommon in all groups.
PubMed-ID: 22366981
http://dx.doi.org/10.1007/s00268-012-1471-x
Completion Thyroidectomy: Effect of Timing on Clinical Complications and Oncologic Outcome in Patients With Differentiated Thyroid Cancer. 
World J Surg, 36(5):1168-73.
Glockzin G, Hornung M, Kienle K, Thelen K, Boin M, Schreyer AG, Lighvani HR, Schlitt HJ, Agha A. 2012.
BACKGROUND: Despite improved preoperative diagnostics, incidental postoperative detection of differentiated thyroid cancer in the final histology is still common. In most of these cases, completion thyroidectomy is recommended by national and international guidelines, although secondary surgery is associated with an increased operative risk. The optimal timing of completion thyroidectomy is still controversial. METHODS: Between January 1993 and December 2009, a total of 128 patients underwent completion thyroidectomy for differentiated thyroid carcinoma: papillary (n = 87) and follicular (n = 41). These patients were divided into five groups according to the time of the completion thyroidectomy after primary surgery (groups A, 1-3 days; B, 4-7 days; C, 1-7 weeks; D, 7-12 weeks; E, >3 months). Clinical complications and oncologic outcomes were analyzed. The mean follow-up was 82.5 +/- 17 months. RESULTS: The overall rates of transient and persistent postoperative hypocalcemia were 7.0 and 3.1%, respectively. The rates of persistent hypocalcemia were significantly increased in groups B, C, and D in comparison to those in groups A and E (p < 0.003). The hypocalcemia rates were 7.1, 4.5, and 3.8% versus 0%, respectively. Transient or persistent vocal cord paresis was observed in eight (6.2%) and four patients (3.1%), respectively. The incidence of persistent vocal cord paresis (VCP) was significantly higher in groups B, C, and D than in groups A and E (p < 0.003). The VCP rates were 7.1, 4.5, and 3.8% versus 0%, respectively. There was no significant difference regarding survival or recurrence among the five groups. CONCLUSIONS: Considering perioperative morbidity and oncologic outcomes, completion thyroidectomy should be performed either within 3 days or beyond 3 months after primary surgery.
PubMed-ID: 22366982
http://dx.doi.org/10.1007/s00268-012-1484-5
Prospective Electromyographic Evaluation of Functional Postthyroidectomy Voice and Swallowing Symptoms.
World J Surg, 36(6):1354-60.
Lombardi CP, D'Alatri L, Marchese MR, Maccora D, Monaco ML, De CC, Raffaelli M. 2012.
BACKGROUND: Voice and swallowing symptoms following thyroidectomy in the absence of any demonstration of laryngeal nerves injury are usually considered a functional outcome of uncomplicated operations, mainly related to scar formation and emotional reaction. They could be related to unapparent laryngeal nerve or cricothyroid (CT) muscle injuries detectable only by laryngeal electromyography (LEMG). We correlated such symptoms with LEMG patterns. METHODS: A total of 33 consenting patients undergoing total thyroidectomy (TT) were enrolled. Video-strobolaryngoscopy (VSL), acoustic voice analysis (AVA), and maximum phonation time (MPT) were performed preoperatively and 3 months postoperatively. Subjective evaluation of voice (Voice Impairment Score, or VIS) and swallowing (Swallowing Impairment Score, or SIS) were obtained preoperatively and 1 and 3 months postoperatively. At 1 month postoperatively LEMG was performed examining thyroarytenoid (TA) and CT muscles to evaluate the inferior laryngeal nerve (ILN) and the external branch of the superior laryngeal nerve (EBSLN), respectively. RESULTS: One patient experienced transient vocal cord palsy and was excluded. The remaining 32 patients completed the postoperative evaluation. No significant difference was found between preoperative and postoperative AVA and MPT parameters. Mean VIS was significantly worse than preoperatively 1 and 3 months after TT. No significant difference was found between preoperative and postoperative SIS. LEMG evaluation of TA muscle showed decreased voluntary activity and spontaneous fibrillation potentials in one patient. LEMG of the CT muscle did not reveal any sign of EBSLN injury. CONCLUSIONS: Patients frequently complain of subjective symptoms early after TT. LEMG demonstrated the absence of subclinical laryngeal nerve injury in all but one patient, confirming their functional nature.
PubMed-ID: 22382763
http://dx.doi.org/10.1007/s00268-012-1481-8
Indications for Surgery and Significance of Unrecognized Cancer in Endemic Multinodular Goiter.
World J Surg, 36(6):1286-92.
Lasithiotakis K, Grisbolaki E, Koutsomanolis D, Venianaki M, Petrakis I, Vrachassotakis N, Chrysos E, Zoras O, Chalkiadakis G. 2012.
BACKGROUND: The exclusion of cancer in endemic goiter is often difficult mainly because of the high number of nodules and the as-yet unclear natural history of diagnosed cancer in endemic goiter patients. In a large number of consecutive patients who were to undergo total thyroidectomy for endemic multinodular goiter, we assessed indications for surgery and thyroid cancer outcome. METHODS: All patients who were to undergo total thyroidectomy for diffuse multinodular goiter on histological examination between January 1990 and October 2008 were evaluated. RESULTS: Of the 1,161 patients included in the study, 252 were cases of thyroid cancer (21.7%). Sensitivity of thyroid ultrasound (US) and fine-needle aspiration cytology (FNAC) for cancer detection was 30.3 and 64.1%, respectively. Differentiated thyroid carcinoma accounted for most of the tumors (96%), with 54.8% of them being papillary microcarcinomas, while bilateral-multicentric cancer occurred in 20.3%. In multivariate analysis, younger age (p = 0.06), sonographic findings (p = 0.03), and presence of histological thyroiditis (p = 0.09) were independently associated with the occurrence of tumors with diameter greater than 2 cm. The percentage of transient and permanent postoperative complications were approximately 25 and below 2%, respectively. After a median follow-up time of 78.5 months, overall recurrence rate was 6.7% and disease-specific mortality was 1.2%. CONCLUSION: As US and FNAC did not consistently detect cancer in patients with diffuse multinodular goiter in our endemic area, evidence-based indications for surgery in this group of patients is needed, although radical surgery and favorable tumor histology offer favorable outcomes in commonly diagnosed thyroid cancer after total thyroidectomy for endemic multinodular goiter.
PubMed-ID: 22395348
http://dx.doi.org/10.1007/s00268-012-1554-8
A Prospective Evaluation of Quick Intraoperative Parathyroid Hormone Assay at the Time of Skin Closure in Predicting Clinically Relevant Hypocalcemia After Thyroidectomy.
World J Surg, 36(6):1300-6.
Lang BH, Yih PC, Ng KK. 2012.
BACKGROUND: Post-thyroidectomy hypocalcemia is a major contributing factor in delayed hospital discharge and dissuading surgeons from ambulatory thyroidectomy. We prospectively evaluated the accuracy and reliability of quick parathyroid hormone level measurement at skin closure (PTH-SC) in predicting clinically relevant hypocalcemia (i.e., patients requiring calcium +/- calcitriol supplements on hospital discharge). METHODS: Of the 117 patients who underwent a total or completion total thyroidectomy and PTH-SC, 17 (14.5 %) had hypocalcemic symptoms or adjusted calcium <1.90 mmol/L requiring calcium and/or calcitriol supplements on discharge. Serum calcium was checked regularly in the perioperative period until stabilization and an additional quick PTH was checked on the following morning (PTH-D1). Univariate and multivariate analyses were performed to evaluate potential preoperative clinicopathologic factors and postoperative day 0 biochemical indicators. Youden's index and the area under the ROC curve (AUC) were used to determine the best cutoff value and predictability of significant variables or criteria, respectively. RESULTS: In the multivariate analysis, low preoperative adjusted calcium (p = 0.041) and low PTH-SC (p = 0.001) were the two independent variables associated with hypocalcemia. PTH-SC (</=1 or >1 pmol/L) had a higher specificity (95.0 %) and AUC (0.887) than serial calcium monitoring or PTH-D1 alone. Although 3/98 of patients with PTH-SC >1 pmol/L required calcium supplements on discharge, they required only the minimum amount to maintain normocalcemia. CONCLUSION: PTH-SC is an accurate and reliable means of predicting clinically relevant hypocalcemia. It would be reasonable to discharge those with PTH-SC >1 pmol/L on the same operative day as the risk of life-threatening hypocalcemia would seem unlikely.
PubMed-ID: 22399155
http://dx.doi.org/10.1007/s00268-012-1561-9
Biological Relevance of Medullary Thyroid Microcarcinoma.
J Clin Endocrinol Metab, 97(5):1547-53.
Machens A, Dralle H. 2012.
CONTEXT: The clinical relevance of medullary thyroid microcarcinoma, a calcitonin-secreting malignancy, as a valid target for biochemical screening programs has been called into doubt. OBJECTIVE: This investigation aimed at clarifying the intensity of lymphatic spread and exploring the potential for biochemical cure in medullary thyroid microcarcinoma. DESIGN: This was a retrospective analysis. SETTING: The setting was a tertiary referral center. PATIENTS: Included were 233 patients with hereditary (126 patients) or sporadic (107 patients) medullary thyroid microcarcinoma. INTERVENTIONS: The intervention was compartment-oriented surgery. MAIN OUTCOME MEASURE: Clinical-histopathological variables were stratified by primary tumor diameter (2-mm increments) and biochemical cure. RESULTS: With incremental tumor diameter, increasingly more patients with medullary thyroid microcarcinoma harbored lymph node metastases: from 6 to 62% of patients (P < 0.001) for hereditary and from 13 to 43% of patients (P = 0.01) for sporadic disease. The corresponding biochemical cure rates declined from 96 to 71% (P = 0.001) and from 85 to 77% (P = 0.01). Distant disease (two instances of lung metastasis and one instance of bone and liver metastasis) was exceptional, affecting 1.3% of patients with medullary thyroid microcarcinoma. Strongest predictors of a patient's failure to achieve normal calcitonin serum levels were positive nodal status (79 vs. 11% in hereditary and 79 vs. 12% in sporadic disease; both P < 0.001) and the number of involved nodes (means of 6.6 vs. 0.3 nodes in hereditary and 8.8 vs. 0.4 nodes in sporadic disease; both P < 0.001). CONCLUSIONS: Sporadic and hereditary medullary thyroid microcarcinoma carry a significant risk of lymph node metastasis and postoperative calcitonin elevation.
PubMed-ID: 22399508
http://dx.doi.org/10.1210/jc.2011-2534
A Novel Definition of Extrathyroidal Invasion for Patients With Papillary Thyroid Carcinoma for Predicting Prognosis.
World J Surg, 36(6):1231-40.
Hotomi M, Sugitani I, Toda K, Kawabata K, Fujimoto Y. 2012.
OBJECTIVES: Extrathyroidal invasion is one of the most significant risk factors for patients with papillary thyroid carcinoma (PTC). The purpose of this study was to evaluate a novel definition of extrathyroidal invasion for patients with PTC as a method for predicting a patient's prognosis. METHODS: The prospective study was conducted for consecutive 930 patients with primary PTC who received surgery during 1993-2009. We defined only patients who had preoperative recurrent laryngeal nerve palsy or patients in whom the tumor had invaded to the mucosa of the trachea and/or esophagus as Ex3. Patients with minimal invasion were classified as Ex1, and patients with massive invasion, when we could shave off the tumors, were classified as Ex2. Patients without extrathyroidal invasion were classified as Ex0. RESULTS: Patients classified Ex3 showed significantly shorter disease-free survival (p = 0.03) and disease-specific survival (p = 0.007) than patients classified Ex2. The time to recurrence at resection sites was shorter in patients classified Ex3 than in patients classified Ex2 (p = 0.02). The time to death due to distant metastasis of patients classified Ex3 was significantly shorter than that of patients classified Ex2 (p = 0.02). Within the patients classified Ex3, disease-specific survival of patients with invasion to other nearby structures was shorter than that of patients with invasion to only recurrent laryngeal nerve (p = 0.008). CONCLUSIONS: The degree and site of invasion is an important prognostic factor for PTC. Our novel classification of extrathyroidal invasion is valuable in predicting the prognosis of PTC.
PubMed-ID: 22402972
http://dx.doi.org/10.1007/s00268-012-1518-z
Cosmesis and Body Image After Minimally Invasive or Open Thyroid Surgery.
World J Surg, 36(6):1279-85.
Bokor T, Kiffner E, Kotrikova B, Billmann F. 2012.
BACKGROUND: Minimally invasive techniques, such as laparoscopic appendectomy or minimally invasive thyroid surgery, are thought to produce better cosmetic results. However, cosmesis in thyroid surgery was rarely investigated using a standardized approach. The objectives of this study were to evaluate body image and cosmesis in patients who had either minimally invasive (MI) or conventional open (CO) thyroid surgery. METHODS: Two hundred fifty patients of 540 participated (46.3 %): 50 patients (20.0 %) had MI thyroid surgery and 200 (80.0 %) had CO thyroid surgery. The patients filled out a body image questionnaire that investigated body image, cosmesis, and self-confidence. SPSS 19.0 software was used for statistical analysis. RESULTS: Although the mean incision size was significantly shorter in the MI group than in the CO group (2.8 vs. 3.5 cm), the mean scores from the body image questionnaire (body image score, cosmetic score, and self-confidence score) were similar for both groups (p > 0.05). No significant differences in postoperative complications were observed in these groups (p > 0.05). CONCLUSIONS: Studies in the literature that evaluate body image and cosmesis in thyroid surgery using standardized methods are scarce. In our department, the results of a questionnaire showed that the MI approach has no advantage for body image and cosmesis over the CO approach. Further prospective randomized studies using different tools with a larger sample size are needed to investigate the use of MI procedures for thyroid surgery.
PubMed-ID: 22407089
http://dx.doi.org/10.1007/s00268-012-1563-7
Intraoperative Neuromonitoring Does Not Reduce the Incidence of Recurrent Laryngeal Nerve Palsy in Thyroid Reoperations: Results of a Retrospective Comparative Analysis.
World J Surg, 36(6):1348-53.
Alesina PF, Rolfs T, Hommeltenberg S, Hinrichs J, Meier B, Mohmand W, Hofmeister S, Walz MK. 2012.
PURPOSE: Recurrent laryngeal nerve (RLN) palsy is the major concern of reoperative thyroid surgery, and the introduction of neuromonitoring could reduce the rate of this complication. The present study is a retrospective analysis of the experience with completion thyroidectomy with and without neuromonitoring in a referral center. METHODS: Between October 1999 and April 2011, 246 patients [37 men, 209 women; mean age, 55 +/- 12.5 (range, 25-80) years] underwent 250 reoperations for recurrent goiter (n = 203), hyperthyroidism (n = 26), or recurrent thyroid cancer (n = 17). The mean interval between the initial and the reoperative procedure was 17.5 years. According to the availability of the neuromonitoring system and to the surgeon preference, 91 operations were performed with neuromonitoring (NM-group), whereas 159 were performed with direct nerve visualization (NV-group) alone. Patients' characteristics, perioperative data, and postoperative complications were collected in a prospectively maintained database. RESULTS: In the NM-group, 51 unilateral and 40 bilateral resections were performed. The NV-group included 122 unilateral and 37 bilateral procedures. The number of nerves at risk after previous surgery was 128 (NM-group) and 161 (NV-group), respectively. We registered eight RLN palsy in the NM-group (6.2 %) and four in the NV-group (2.5 %; p = 0.1). CONCLUSIONS: The routine use of intraoperative neuromonitoring seems not to reduce the incidence of RLN during redo thyroid surgery, at least in the setting of a tertiary referral center.
PubMed-ID: 22411090
http://dx.doi.org/10.1007/s00268-012-1548-6
Clinical Features, Treatment, and Long-Term Outcome of Papillary Thyroid Cancer in Children and Adolescents Without Radiation Exposure.
World J Surg, 36(6):1241-6.
Enomoto Y, Enomoto K, Uchino S, Shibuya H, Watanabe S, Noguchi S. 2012.
BACKGROUND: Cancer of the thyroid gland is rare in children and adolescents. A history of neck irradiation is a well-established risk factor for tumor development, and most previous reports focused on cases that were induced by radiation exposure. We present here a retrospective review of the clinical features, treatment, and long-term outcome of children and adolescents with papillary thyroid cancer (PTC) without a history of radiation exposure who were treated at our institution over a period of ~50 years. METHODS: We retrospectively investigated 142 PTC patients without an irradiation history who were younger than 20 years of age when treated from 1961 to 2005 (17 males and 125 females; mean age = 16.3 +/- 2.7 years; follow-up = 21.8 +/- 12.0 years). The clinicopathological results were evaluated using the medical records. Disease-free survival (DFS) and cause-specific survival (CSS) were assessed with the Kaplan-Meier method and compared with the log-rank test. Parametric analyses were performed using Student's t test and nonparametric analyses were performed using the Mann-Whitney U test. RESULTS: At diagnosis, three patients had distant lung metastasis and 33 had gross neck lymph node (LN) metastasis. All patients were treated with surgery (hemi/partial thyroidectomy in 45 patients, subtotal thyroidectomy in 85, total thyroidectomy in 12, no LN dissection in 50, central compartment dissection in 20, and modified radical neck dissection in 72), and postoperative external beam radiation therapy was administered to 59. Postoperative ablative therapy using I(131) was not performed in this series. Recurrence was found for regional LN (n = 25), lung (n = 9), remnant thyroid (n = 5), and others (n = 4). DFS and CSS at 40 years were 74.1 and 97.5%, respectively. DFS was significantly worse in patients aged <16 years with a family history of thyroid cancer, preoperative neck gross LN metastasis, maximum tumor diameter, and extrathyroidal invasion. Preoperative gross neck LN metastasis and distant metastasis at diagnosis were significant factors for CSS. No other factors contributed to DFS and CSS. When the clinical features of children and adolescents were compared, the incidence of preoperative gross neck LN metastasis and distant metastasis at diagnosis and tumors with a maximum diameter >10 mm were significantly higher in the children group than in the adolescent group. DFS was significantly shorter in the children group than in the adolescent group, but no significant difference was found in CSS between these two groups. CONCLUSIONS: The prognosis of PTC in children and adolescents is excellent, regardless of the extent of thyroidectomy and LN dissection. We recommend that only children or adolescents with preoperative gross neck LN metastasis and distant metastasis at diagnosis should be subjected to postoperative ablative therapy.
PubMed-ID: 22411092
http://dx.doi.org/10.1007/s00268-012-1558-4
A Population-Based Prospective Cohort Study of Complications After Thyroidectomy in the Elderly.
J Clin Endocrinol Metab, 97(5):1645-53.
Grogan RH, Mitmaker EJ, Hwang J, Gosnell JE, Duh QY, Clark OH, Shen WT. 2012.
CONTEXT: Data on the risk of postthyroidectomy complications in elderly patients are sparse, unclear, and conflicting. OBJECTIVE: We sought to use a population-based cohort to determine whether thyroid operations in the elderly are as safe as those done in younger patients. DESIGN: This was a prospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program database from 2005 to 2008, with 30-d postoperative follow-up. SETTING: The American College of Surgeons National Surgical Quality Improvement Program data set contains operative cases from a nationwide sampling of academic and community-based as well as high-volume and low-volume hospitals. PATIENTS: All thyroidectomy and parathyroidectomy patients reported to the database during the study period were included in the analysis resulting in an experimental cohort of 7915 thyroidectomy cases and a control cohort of 3575 parathyroidectomy cases. MAIN OUTCOME MEASURES: We aggregated 83 complications into the following outcome measures: urinary tract infection, wound infection, systemic infection, cardiac complications, pulmonary complications, 30-d mortality, and total hospital length of stay. RESULTS: Increased age is a risk factor for significant pulmonary, cardiac, and infectious complications after thyroidectomy. Elderly patients are twice as likely (odds ratio 2.1, 95% confidence interval 1.4-3.3), and the superelderly are 5 times as likely (odds ratio 4.9, 95% confidence interval 2.5-9.6) to have a complication compared with their young counterparts. Preexisting comorbidities are effect modifiers and increase the risk of complications even further. CONCLUSIONS: Elderly thyroidectomy patients are at increased risk for major systemic complications. A systematic approach to the care of elderly thyroidectomy patients is necessary to minimize their risk of serious postoperative complications.
PubMed-ID: 22419716
http://dx.doi.org/10.1210/jc.2011-1162
Cost Impact of Molecular Testing for Indeterminate Thyroid Nodule Fine-Needle Aspiration Biopsies.
J Clin Endocrinol Metab, 97(6):1905-12.
Yip L, Farris C, Kabaker AS, Hodak SP, Nikiforova MN, McCoy KL, Stang MT, Smith KJ, Nikiforov YE, Carty SE. 2012.
INTRODUCTION: Molecular testing of fine-needle aspiration (FNA) results helps diagnose thyroid cancer, although the additional cost of this adjunct has not been studied. We hypothesized that FNA molecular testing of two indeterminate categories (follicular lesion of undetermined significance and follicular/Hurthle cell neoplasm) can be cost saving. METHODS: For a hypothetical group of euthyroid patients with a 1-cm or larger solitary thyroid nodule, a decision-tree model was constructed to compare the estimated costs of initial evaluation according to the current American Thyroid Association guidelines, either with molecular testing (MT) or without [standard of care (StC)]. Model endpoints were either benign FNA results or definitive histological diagnosis. RESULTS: Molecular testing added $104 per patient to the overall cost of nodule evaluation (StC $578 vs. MT $682). In this distributed cost model, MT was associated with a decrease in the number of diagnostic lobectomies (9.7% vs. StC 11.6%), whereas initial total thyroidectomy was more frequent (18.2% vs. StC 16.1%). Although MT use added a diagnostic cost of $5031 to each additional indicated total thyroidectomy ($11,383), the cumulative cost was still less than the comparable cost of performing lobectomy ($7684) followed by completion thyroidectomy ($11,954) in the StC pathway, when indicated by histological results. In sensitivity analysis, savings were demonstrated if molecular testing cost was less than $870. CONCLUSIONS: Molecular testing of cytologically indeterminate FNA results is cost saving predominantly because of reduction in two-stage thyroidectomy. Appropriate use of emerging molecular testing techniques may thus help optimize patient care, improve resource use, and avoid unnecessary operation.
PubMed-ID: 22419727
http://dx.doi.org/10.1210/jc.2011-3048
Combining Early Postoperative Parathyroid Hormone and Serum Calcium Levels Allows for an Efficacious Selective Post-Thyroidectomy Supplementation Treatment.
World J Surg, 36(6):1307-13.
Raffaelli M, De CC, Carrozza C, D'Amato G, Zuppi C, Bellantone R, Lombardi CP. 2012.
BACKGROUND: Optimal treatment protocol to prevent symptomatic hypocalcemia following total thyroidectomy is still matter of debate. We prospectively evaluated the efficacy of a selective supplementation protocol based on both early postoperative intact parathyroid hormone (iPTH) and serum calcium levels. METHODS: Two hundred thirty consecutive patients were divided in three different groups of treatment according to iPTH levels 4 h after total thyroidectomy (4 h-iPTH) and serum calcium levels in the first postoperative day (1PO-Ca): group A (4 h-iPTH > 10 pg/ml, 1PO-Ca >/= 8.5 mg/dl), no treatment; group B (4 h-iPTH > 10 pg/ml, 1PO-Ca < 8.5 mg/dl), oral calcium (OC) 3 g per day; and group C (4 h-iPTH </= 10 pg/ml), OC 3 g + calcitriol (VD) 1 mug per day. Development of biochemical and/or symptomatic hypocalcemia was evaluated. RESULTS: Fifty-nine patients (25.6%) had subnormal 4 h-iPTH levels (</=10 pg/ml) (group C). Among patients with normal 4 h-iPTH levels, 25 (10.9%) had subnormal 1PO-Ca (<8.5 mg/dl) (group B). The remaining 146 patients (63.5%) had normal 4 h-iPTH and 1PO-Ca levels (group A). One patient in group A, 2 in group B, and 18 in group C developed biochemical hypocalcemia. Only one patient in group C experienced major symptoms. Treatment was discontinued within 1 month in all the patients in group B. At a mean follow-up of 303 days, five patients in group C were still under supplementation treatment. CONCLUSION: The proposed supplementation protocol seems efficacious in preventing symptomatic hypocalcemia. It could allow a safe and early discharge of most patients, thus avoiding the constraints and the costs of routine supplementation.
PubMed-ID: 22422171
http://dx.doi.org/10.1007/s00268-012-1556-6
Assessment of Swallowing Function Impairment in Patients With Benign Goiters and Impact of Thyroidectomy: a Case Control Study.
World J Surg, 36(6):1293-9.
Sabaretnam M, Mishra A, Chand G, Agarwal G, Agarwal A, Verma AK, Mishra SK. 2012.
BACKGROUND: Swallowing-related quality of life (QoL) in patients with benign thyroid goiters is not much studied. The aim of this study was to assess swallowing function impairment in patients with benign goiters, compare it to a control population, and also find the impact of thyroidectomy and various factors on the outcome of swallowing function. METHODS: We performed a prospective case-control study from September 2009 to September 2011 which consisted of 124 patients who were to undergo primary thyroid surgery and 100 age- and sex-matched controls. A translated and validated modified swallowing quality-of-life (SWAL-QOL) questionnaire was used to assess patients' perception of dysphagia. Presurgery scores of patients and controls and pre- and postsurgery scores (>6 months after surgery) of patients were compared. RESULTS: The mean age of males and females in the control and patient groups were 37.7 vs. 39.5 years and 37.4 vs. 39.8 years, respectively. Twelve patients (9.7%) complained of dysphasia at presentation. Sixty-three patients (50.8%) underwent total thyroidectomy and 61 (49.2%) had hemithyroidectomy at the time of initial evaluation, 75, 23.4, and 1.6% of patients were euthyroid, hyperthyroid, and hypothyroid, respectively. Presurgery scores of patients in all of the 11 domains of the SWAL-QOL were lower compared to those of controls. Comparing separately with the matched controls, females had significant differences in nine domains (except for sleep and fatigue) of the SWAL-QOL questionnaire but males did not. Postoperatively, both male and female patients showed significant improvement in the scores of all the domains. Female gender, hyperthyroidism, thyroid nodularity, retrosternal extension, procedure, and weight of the resected specimen were the factors associated with significant improvement in various domains. CONCLUSION: Dysphagia seems to be an underestimated problem in patients with benign goiters. Uncomplicated thyroidectomy results in significant improvement in swallowing-related QoL irrespective of patient profile and extent of thyroidectomy.
PubMed-ID: 22422173
http://dx.doi.org/10.1007/s00268-012-1562-8
"Doctor, My Thyroid Is Choking Me": Common Sense and Scientific Inquiry.
Arch Surg, 147(7):626.
Schneider D, Chen H. 2012.
PubMed-ID: 22430098
http://dx.doi.org/10.1001/archsurg.2012.236
Level VI Lymph Node Dissection Does Not Decrease Radioiodine Uptake in Patients Undergoing Radioiodine Ablation for Differentiated Thyroid Cancer.
World J Surg, 36(6):1255-61.
Yoo D, Ajmal S, Gowda S, Machan J, Monchik J, Mazzaglia P. 2012.
BACKGROUND: In patients with well-differentiated thyroid cancer, the incidence of pathologic central compartment lymph node metastases is reported to be approximately 50%. Recently level VI lymph node dissection has been advocated as a means of reducing recurrence rates in these patients, even if there are no clinically apparent nodal metastases. This study investigates whether level VI lymph node dissection decreases the percent radioiodine uptake when patients undergo radioiodine ablation. METHODS: All thyroid cancer patients entered into the endocrine surgery database at a tertiary care center from 2006 to 2010 were reviewed. Those treated with radioactive iodine were analyzed with respect to performance of a central compartment lymph node dissection and the percent uptake of radioiodine ((131)I) on the preablation scan at 72 h. RESULTS: There were 277 patients with well-differentiated thyroid cancer who underwent radioiodine ablation. In all, 75% were female, and the mean age was 47.7 years. A total of 87 patients underwent total thyroidectomy and level VI lymph node dissection (TT + LVIND). The mean number of level VI nodes resected was 6 (1-27), and 60.9% of patients had nodal metastases. Altogether, 190 had a total thyroidectomy (TT) only, and the median number of nodes resected was 0 (0-10). The percent uptake of radioiodine on the preablation scan was 0.93% in patients who had undergone TT + LVIND and 1.2% in those with TT alone (p = 0.17). The median number of radioactive foci noted within the thyroid bed was two in both groups (p = 0.64). The mean preablation thyroglobulin levels, measured after thyroxine withdrawal or thyrogen stimulation, were 4.0 ng/ml in the TT + LVIND group versus 4.7 ng/ml in the TT group (p = 0.07). The average ablative dose of (131)I was 111.8 mCi in the dissection group and 98.5 mCi in the TT-only group. CONCLUSIONS: There is no evidence that uptake of (131)I is reduced by performance of a central neck dissection in patients with well-differentiated thyroid cancer. Preablation thyroglobulin levels were not altered by level VI lymph node dissection.
PubMed-ID: 22430670
http://dx.doi.org/10.1007/s00268-012-1507-2
Activation of the RAS/RAF/ERK Signaling Pathway Contributes to Resistance to Sunitinib in Thyroid Carcinoma Cell Lines.
 J Clin Endocrinol Metab, 97(6):E898-E906.
Piscazzi A, Costantino E, Maddalena F, Natalicchio MI, Gerardi AM, Antonetti R, Cignarelli M, Landriscina M. 2012.
CONTEXT: Sunitinib is currently being evaluated in advanced human thyroid carcinomas, based on the rationale that the vascular endothelial growth factor and platelet-derived growth factor receptors and the RET/PTC rearrangement are valuable targets for the treatment of this malignancy. However, criteria for selecting thyroid tumors that may benefit from sunitinib are lacking. DESIGN: The effect of activating somatic mutations in the KRAS and BRAF genes on the responsiveness to sunitinib was evaluated in a panel of thyroid cancer cell lines harboring wild-type KRAS and BRAF genes, the RET/PTC1 rearrangement, the G12R KRAS, or the V600E BRAF mutation. RESULTS: Sunitinib was found to selectively inhibit cell proliferation, induce cell accumulation in the G0-G1 phase, and inhibit the phosphorylation of ERK1/2 in both KRAS/BRAF wild-type thyroid cancer cells and in tumor cells harboring the RET/PTC rearrangement, whereas it was completely ineffective in.
PubMed-ID: 22442268
http://dx.doi.org/10.1210/jc.2011-3269
Day-Case Thyroid Surgery.
Br J Surg, 99(6):741-3.
Doran HE, Palazzo F. 2012.
PubMed-ID: 22467490
http://dx.doi.org/10.1002/bjs.8756
Circulating MicroRNA Profiles As Potential Biomarkers for Diagnosis of Papillary Thyroid Carcinoma.
J Clin Endocrinol Metab, 97(6):2084-92.
Yu S, Liu Y, Wang J, Guo Z, Zhang Q, Yu F, Zhang Y, Huang K, Li Y, Song E, Zheng XL, Xiao H. 2012.
CONTEXT: There are no known effective and reliable biomarkers to distinguish benign thyroid nodules from papillary thyroid carcinomas (PTC). Previous studies have indicated that serum microRNA (miRNA) profiles may be diagnostic and/or prognostic markers for numerous other cancers. OBJECTIVE: We studied circulating miRNA profiles in patients with PTC or benign nodules and healthy controls to identify serum miRNA that may be useful as markers for PTC. DESIGN, SETTING, AND PARTICIPANTS: Genome-wide serum miRNA expression profiles were determined using Solexa sequencing followed by extensive quantitative RT-PCR validation in 245 subjects (106 patients with PTC, 95 patients with benign nodules, and 44 healthy controls). A panel of miRNA was used to assess the expression of specific miRNA in the sera and thyroid tissues of patients with PTC or benign nodules. RESULTS: The expression of serum let-7e, miR-151-5p, and miR-222 was significantly increased in PTC cases relative to benign cases and healthy controls. Receiver operating characteristic curve analyses indicated that use of these three miRNA had a high diagnostic sensitivity and specificity for PTC. Serum let-7e, miR-151-5p, and miR-222 levels were found to be well correlated with certain clinicopathological variables, such as nodal status, tumor size, multifocal lesion status, and Tumor-Node-Metastasis stage. Expression of serum miR-151-5p and miR-222 in a subset of PTC patients decreased significantly after tumor excision. Increased expression of miR-151-5p and miR-222 was also found in the tissue of PTC patients. CONCLUSIONS: Our study demonstrates that serum miRNA profiles may be used as novel and minimally invasive diagnostic markers for PTC.
PubMed-ID: 22472564
http://dx.doi.org/10.1210/jc.2011-3059
Advances in the Follow-Up of Differentiated or Medullary Thyroid Cancer.
Nat Rev Endocrinol, 8(8):466-75.
Elisei R, Pinchera A. 2012.
The long-term survival of patients with thyroid cancer and the possibility of tumour recurrence up to 30-40 years after the achievement of a disease-free status illustrate the importance of lifelong follow-up in these individuals. This Review discusses the most innovative aspects of follow-up protocols for patients with differentiated thyroid cancer, that is, of papillary or follicular hystotype, and those with medullary thyroid cancer. Particular focus is placed on the relevance of new ultrasensitive assays for thyroglobulin measurement and the option of using recombinant human TSH to stimulate thyroglobulin secretion. Methods to compensate for the loss of diagnostic significance of serum thyroglobulin levels in patients with differentiated thyroid cancer and circulating anti-thyroglobulin antibodies are highlighted, as well as the role of the postoperative calcitonin stimulation test and the clinical relevance of determining the doubling time of calcitonin and carcinoembryonic antigen in patients with medullary thyroid cancer. Moreover, this Review gives some insights into the role of molecular thyroid cancer testing, both for prognostic and for therapeutic purposes. Finally, a general overview of traditional imaging procedures, such as neck ultrasonography, CT, MRI and bone scintigraphy, is provided alongside a comparison with new nuclear imaging tests such as PET.
PubMed-ID: 22473335
http://dx.doi.org/10.1038/nrendo.2012.38
Risk Factors for Medically Treated Hypocalcemia After Surgery for Graves' Disease: a Swedish Multicenter Study of 1,157 Patients.
World J Surg, 36(8):1933-42.
Hallgrimsson P, Nordenstrom E, Almquist M, Bergenfelz AO. 2012.
BACKGROUND: For reasons that remain unclear, surgery for Graves' disease is associated with a higher risk of hypocalcemia than surgery for benign atoxic goiter. In the present study, we evaluated risk factors for postoperative hypocalcemia in patients undergoing operation for Graves' disease. METHODS: Data from 1,157 patients who underwent operation for Graves' disease between 2004 and 2008 were extracted from the Scandinavian database for Thyroid and Parathyroid Surgery. Risk factors for postoperative hypocalcemia (in-hospital i. v. calcium; treatment with vitamin D analog at discharge, at 6 weeks, and at 6 months postoperatively) were evaluated by logistic regression analysis. RESULTS: Risk factors for i. v. calcium were low hospital volume of thyroid surgery (odds ratio [OR]: 95 % confidence interval [95 % CI], 0.99: 0.99-1.00), age (0.95: 0.91-1.00), operative time (1.02: 1.01-1.02), university hospital (12.91: 2.68-62.30), and reoperation for bleeding (10.32: 1.51-70.69). The risk for treatment with vitamin D at discharge increased with operative time (1.01: 1.00-1.02), excised gland weight (1.01: 1.00-1.01), parathyroid autotransplantation (5.19: 2.28-11.84), and reoperation for bleeding (12.00: 2.43-59.28). At 6 weeks, vitamin D medication was associated with gland weight (1.00: 1.00-1.01), and preoperative medication with beta-blockers (4.20: 1.67-10.55). At 6 months, vitamin D medication was associated with gland weight (1.00: 1.00-1.01) and reoperation for bleeding (10.59: 1.58-71.22). CONCLUSIONS: Risk factors for medically treated hypocalcemia varied at different times of follow-up. Young age, operative time, type of hospital, and parathyroid autotransplantation were associated with early postoperatively hypocalcemia. Preoperative beta-blocker treatment was a risk factor at the first follow-up. At early and late follow-up, gland weight and reoperation for bleeding were associated with medically treated hypocalcemia.
PubMed-ID: 22476788
http://dx.doi.org/10.1007/s00268-012-1574-4
Do We Overtreat Post-Thyroidectomy Hypocalcemia?
World J Surg, 36(7):1503-8.
Huang SM. 2012.
BACKGROUND: Calcium and calcitriol supplements are standard for patients with post-thyroidectomy serum calcium <2.0 mmol/L; however, we wondered whether we overtreat post-thyroidectomy hypocalcemia with intraoperative parathyroid hormone (PTH). We examined quick-intraoperative intact PTH (QiPTH) assay results to find a suitable treatment for post-thyroidectomy hypocalcemia. METHODS: We studied 197 bilateral thyroidectomy patients. Post-thyroidectomy hypocalcemia was defined as serum calcium <2.0 mmol/L. A QiPTH assay was done 15 min after the thyroidectomy (QiPTH(15)), and hypoparathyroidism was defined as PTH <15 ng/L. The QiPTH(15) assay was used to determine the effects of the thyroidectomy on postoperative PTH levels and serum calcium levels. The natural course and medical response of hypocalcemia was observed in patients with a QiPTH(15) >/= 15 ng/L. RESULTS: None of the 187 patients with a QiPTH(15) >/= 15 ng/L developed postoperative hypoparathyroidism. However, 79 patients developed transient hypocalcemia, and those with Graves' disease (47/94) had significantly (p < 0.05) higher hypocalcemia than those with non-Graves' thyroid disease (32/93). The serum calcium of these 79 patients declined to its lowest level within the first postoperative 18 h. Seven patients with serum calcium <1.75 mmol/L were successfully treated using a calcium supplement only, and the others recovered spontaneously without treatment. CONCLUSIONS: When post-thyroidectomy QiPTH(15) was >/= 15 ng/L, postoperative hypoparathyroidism was excluded, but more than one-third of the patients developed post-thyroidectomy hypocalcemia. However, most of them recovered without treatment, and a few recovered after taking only a calcium supplement. We believe that using QiPTH(15) results as a guide will prevent overtreatment of post-thyroidectomy hypocalcemia.
PubMed-ID: 22491818
http://dx.doi.org/10.1007/s00268-012-1580-6
The Impact of Age and Gender on Papillary Thyroid Cancer Survival.
J Clin Endocrinol Metab, 97(6):E878-E887.
Jonklaas J, Nogueras-Gonzalez G, Munsell M, Litofsky D, Ain KB, Bigos ST, Brierley JD, Cooper DS, Haugen BR, Ladenson PW, Magner J, Robbins J, Ross DS, Skarulis MC, Steward DL, Maxon HR, Sherman SI. 2012.
CONTEXT: Thyroid cancer predominately affects women, carries a worse prognosis in older age, and may have higher mortality in men. Superimposed on these observations is the fact that most women have attained menopause by age 55 yr. OBJECTIVE: The objective of the study was to determine whether men contribute disproportionately to papillary thyroid cancer (PTC) mortality or whether menopause affects PTC prognosis. DESIGN: Gender-specific mortality was normalized using age-matched subjects from the U.S. population. Multivariate Cox proportional hazard regression models incorporating gender, age, and National Thyroid Cancer Treatment Cooperative Study Group stage were used to model disease-specific survival (DSS). PARTICIPANTS AND SETTING: Patients were followed in a prospective registry. MAIN OUTCOME MEASURE: The relationships between gender, age, and PTC outcomes were analyzed. RESULTS: The unadjusted hazard ratio (HR) for DSS for women was 0.40 [confidence interval (CI) 0.24-0.65]. This female advantage diminished when DSS was adjusted for age at diagnosis and stage with a HR encompassing unity (HR 0.72, CI 0.44-1.19). Additional multivariate models of DSS considering gender, disease stage, and various age groupings showed that the DSS for women diagnosed at under 55 yr was improved over men (HR 0.33, CI 0.13-0.81). However, the HR for DSS increased to become similar to men for women diagnosed at 55-69 yr (HR 1.01, CI 0.42-2.37) and at 70 yr or greater (HR 1.17, CI 0.48-2.85). CONCLUSIONS: Although the overall outcome of women with PTC is similar to men, subgroup analysis showed that this composite outcome is composed of two periods with different outcomes. The first period is a period with better outcomes for women than men when the diagnosis occurs at younger than 55 yr; the second is a period with similar outcomes for both women and men diagnosed at ages greater than 55 yr. These data raise the question of whether an older age cutoff would improve current staging systems. We hypothesize that older age modifies the effect of gender on outcomes due to menopause-associated hormonal alterations.
PubMed-ID: 22496497
http://dx.doi.org/10.1210/jc.2011-2864
Clinical Implication of Highly Sensitive Detection of the BRAF V600E Mutation in Fine-Needle Aspirations of Thyroid Nodules: a Comparative Analysis of Three Molecular Assays in 4585 Consecutive Cases in a BRAF V600E Mutation-Prevalent Area.
J Clin Endocrinol Metab, 97(7):2299-306.
Lee ST, Kim SW, Ki CS, Jang JH, Shin JH, Oh YL, Kim JW, Chung JH. 2012.
CONTEXT: Detection of the BRAF V600E mutation in fine-needle aspiration cytology (FNAC) specimens may increase the value of FNAC. OBJECTIVE: The objectives of the study was to compare the diagnostic performance of BRAF assays that differ in sensitivity and to examine the associations between the BRAF V600E mutation status and the clinicopathological features in papillary thyroid carcinoma (PTC). DESIGN AND SETTING: Three molecular assays were performed in all subjects and compared with regard to FNAC and histology results. PARTICIPANTS: We evaluated 4585 consecutive patients who were found to have malignant or indeterminate thyroid nodules by ultrasonography. OUTCOME MEASURES: All FNAC samples were tested for the BRAF V600E mutation using conventional Sanger sequencing, dual-priming oligonucleotide-PCR, and mutant enrichment with 3'-modified oligonucleotide (MEMO) sequencing. RESULTS: The detection sensitivities of the three molecular assays for the BRAF V600E mutation were 20, 2, and 0.1%, respectively. Compared with conventional Sanger sequencing (n = 673), dual-priming oligonucleotide-PCR and MEMO sequencing detected more tumors with the BRAF V600E mutation (n = 919 and n = 1044, respectively), especially tumors with a benign, indeterminate, or nondiagnostic cytology. All BRAF-positive tumors that were histologically examined were shown to be PTC, regardless of cytology results. The clinical sensitivities of the three assays for detecting PTC were 54.8, 74.4, and 79.7%, respectively. BRAF V600E mutations in microcarcinomas (</= 10 mm) were detected more efficiently as the detection sensitivity of the assay increased (P < 0.001). Tumor size correlated significantly with multifocality, extrathyroidal extension, and lymph node metastasis (P = 0.003, P < 0.001 and P < 0.001, respectively), but the BRAF V600E mutation status was not associated with any of those features. CONCLUSION: Highly sensitive and specific molecular assays such as MEMO sequencing are optimal for detecting the BRAF mutations in thyroid FNAC because these techniques can detect PTC that might be missed by cytology or less sensitive molecular assays.
PubMed-ID: 22500044
http://dx.doi.org/10.1210/jc.2011-3135
Reduction of False-Negative Papillary Thyroid Carcinomas by the Routine Analysis of BRAF(T1799A) Mutation on Fine-Needle Aspiration Biopsy Specimens: a Prospective Study of 814 Thyroid FNAB Patients.
 Ann Surg, 255(5):986-92.
Canadas-Garre M, Becerra-Massare P, Lopez de la Torre-Casares, Villar-del MJ, Cespedes-Mas S, Vilchez-Joya R, Muros-de FT, Garcia-Calvente C, Piedrola-Maroto G, Lopez-Nevot MA, Montes-Ramirez R, Llamas-Elvira JM. 2012.
OBJECTIVES: To evaluate prospectively the usefulness of the routine determination of BRAF(T1799A) mutation on thyroid fine-needle aspiration biopsy (FNAB) to detect cytopathology false negative papillary thyroid carcinomas (PTC) and, therefore, as a tool to improve the sensitivity of the preoperative cytopathological diagnosis of PTC in thyroid nodules. BACKGROUND: FNAB is the most reliable diagnostic test to discriminate between malignant and benign thyroid nodules, but nondiagnostic results remain a clinical management dilemma. BRAF(T1799A) mutation is the most prevalent genetic alteration in thyroid cancers and is specific for PTC, characteristics that make it the most potentially helpful genetic tool to improve the diagnostic accuracy of FNAB. METHODS: An exhaustive recruitment of all patients subjected to thyroid FNAB in our institution during 4 years was performed. BRAF(T1799A) mutation was determined on thyroid FNAB specimens by PCR and restriction fragment length polymorphism, plus direct sequencing in positive samples. RESULTS: BRAF(T1799A) mutation on FNAB detected 47.2% (17/36) of PTC cases. It confirmed preoperatively 45.5% (5/11) of the PTC cases in the indeterminate category and decreased the rate of cytopathology false-negatives in 33.3% (6/18), improving the combined (BRAF(T1799A) mutation + cytopathological analysis) sensitivity of the detection of PTC on FNAB in 16.7%. CONCLUSIONS: BRAF(T1799A) mutation improves the diagnosis of PTC on FNAB, mainly because of the detection of cytopathology false-negatives, and it can be helpful in the routine analysis of thyroid nodules, especially in clinical settings with moderate sensitivity to detect PTC on FNAB.
PubMed-ID: 22504197
http://dx.doi.org/10.1097/SLA.0b013e31824e8d70
A High Percentage of BRAFV600E Alleles in Papillary Thyroid Carcinoma Predicts a Poorer Outcome.
J Clin Endocrinol Metab, 97(7):2333-40.
Guerra A, Fugazzola L, Marotta V, Cirillo M, Rossi S, Cirello V, Forno I, Moccia T, Budillon A, Vitale M. 2012.
CONTEXT: BRAF(V600E) is considered a negative prognostic marker in papillary thyroid carcinoma (PTC), but unexplained conflicting results are present in the literature. In light of the new finding that most PTC consist of a mixture of tumor cells with wild-type and mutant BRAF, we examined the associations between the percentage of BRAF(V600E) alleles and both the clinicopathological parameters at time of diagnosis and the disease outcome in a large series of PTCs. STUDY DESIGN: Tumors from 168 patients with PTC were genotyped for BRAF(V600E) using BigDye Terminator sequencing and pyrosequencing, and the clinical parameters were analyzed. The associations between clinicopathological characteristics, including disease recurrence at follow-up (median 5.1 yr) and the percentage of mutant BRAF alleles were assessed. RESULTS: The observed prevalence of BRAF(V600E) was higher when using pyrosequencing then when using BigDye Terminator sequencing (53.6 vs. 36.9%). In the PTC positive for BRAF(V600E), the percentage of mutant alleles ranged from 5.1 to 44.7% of the total BRAF alleles, with a median of 20.6%. The presence or the percentage of BRAF(V600E) alleles did not correlate significantly with sex, multicentricity, lymph node metastasis, or tumor stage. The percentage of BRAF(V600E) alleles directly correlated with age at diagnosis and tumor volume (R(2) = 0.223, P = 0.039, and R(2) = 0.166, P < 0.001, respectively). The percentage of BRAF(V600E) alleles (P = 0.014), tumor volume (P = 0.012), and lymph node metastasis (P = 0.008) predicted the disease outcome. The odds ratio of recurrence for PTC with BRAF(V600E) alleles of 30% or greater, compared with that for PTC with BRAF(V600E) alleles of less than 30%, was 5.31 (P = 0.002). CONCLUSIONS: A high percentage of BRAF(V600E) alleles defines a PTC molecular subtype and predicts a poorer disease outcome. The analysis of BRAF mutations by pyrosequencing is useful to refine the risk stratification of patients with PTC.
PubMed-ID: 22508706
http://dx.doi.org/10.1210/jc.2011-3106
Secretory Capacity of the Parathyroid Glands After Total Thyroidectomy in Normocalcemic Subjects.
J Clin Endocrinol Metab, 97(7):2341-6.
Anastasiou OE, Yavropoulou MP, Papavramidis TS, Tzouvara C, Triantafyllopoulou K, Papavramidis S, Yovos JG. 2012.
CONTEXT: Hypocalcemia, transient or permanent, represents a common complication after total thyroidectomy, but data on the secretory capacity of the parathyroid glands in thyroidectomized patients without clinical or biochemical hypocalcemia are limited. STUDY DESIGN: To address this issue, we studied the parathyroid response to acute hypocalcemia induced by iv infusion of sodium bicarbonate in normocalcemic patients submitted to total thyroidectomy at the early postoperative period and 3 months later. PATIENTS AND METHODS: Sixty patients who underwent total thyroidectomy for benign thyroid disease and did not develop clinical or biochemical hypocalcemia and hypoparathyroidism postoperatively and 50 healthy volunteers were included in the study. Patients (at 48 h and 3 months after surgery) and controls (after overnight fast) were subjected to a sodium bicarbonate infusion test. RESULTS: In healthy volunteers plasma intact PTH increased significantly at 3 min after infusion (4.42 +/- 0.15 ng/ml vs. 11.22 +/- 0.5 ng/ml, P < 0.001) and gradually returned to baseline values. In the thyroidectomized patients, mean PTH levels were also increased after sodium bicarbonate infusion but to a significantly lesser degree compared with healthy controls (1.77 mean fold increase vs. 2.57 mean fold increase, respectively, P < 0.001). Using as criterion the lowest fold increase of plasma PTH levels at 3 min after infusion observed in healthy volunteers, 38% of the thyroidectomized patients at 48 h after surgery and 6.6% of the patients at 3 months after surgery demonstrated a diminished PTH response to acute hypocalcemia induced by sodium bicarbonate infusion. CONCLUSION: In thyroidectomized patients, normal postoperative calcium and PTH values do not exclude a reduced secretory response of the parathyroids to hypocalcemic stimuli.
PubMed-ID: 22511794
http://dx.doi.org/10.1210/jc.2012-1170
Sentinel Lymph Node Biopsy Using Carbon Nanoparticles for Chinese Patients With Papillary Thyroid Microcarcinoma.
Eur J Surg Oncol, 38(8):718-24.
Hao RT, Chen J, Zhao LH, Liu C, Wang OC, Huang GL, Zhang XH, Zhao J. 2012.
AIMS: To compare the efficacies of methylene blue (MB) and carbon nanoparticles (CNs) as tracers for sentinel lymph node biopsy (SLNB), and assess the value of SLNB in predicting the cervical LN status of patients with thyroid microcarcinoma. METHODS: This retrospective analysis comprised 200 thyroid microcarcinoma patients who underwent intraoperative SLNB. Among them, 100 patients were injected with MB dye. The other 100 patients received a CN suspension injection. Routine pathological examination was performed in all resected specimens. RESULTS: SLNs detected in the experimental and control groups were 126 and 102, respectively, of which the metastatic LNs confirmed by histopathology were 77 and 48, respectively. The staining rate of cervical level VI LNs in the experimental group was significantly higher than that in the control group (P<0.001). For the CN method, the sensitivity, specificity, accuracy rate, and false negative rate were 93.3%, 100%, 97%, and 5.2%, respectively, whereas the corresponding figures for the MB method were 80.6%, 100%, 93%, and 9.9%, respectively. The positive rate of cancer metastases for SLNs in the experimental group was 61.1%, which is significantly higher than that in the control group (47.1%; P=0.034). CONCLUSIONS: In contrast to the MB method, CNs can maintain the durability of SLN imaging and accurately forecast the LN status of patients with thyroid microcarcinoma; in addition, the CN method was found to be feasible and repeatable. The CN method better aids the screening and selection of patients who are most likely to benefit from cervical LN dissection.
PubMed-ID: 22521260
http://dx.doi.org/10.1016/j.ejso.2012.02.001
Endocrine Surgeon-Performed US Guided Thyroid FNAC Is Accurate and Efficient.
World J Surg, 36(8):1947-52.
Al-azawi D, Mann GB, Judson RT, Miller JA. 2012.
BACKGROUND: Ultrasound guided fine needle aspiration cytology (US-FNAC) is a key diagnostic technique used to assess thyroid nodules. This procedure has been the domain of radiologists, but it is increasingly performed by endocrine surgeons. In the present study we aimed to assess the accuracy and clinical efficiency of US-FNAC performed by endocrine surgeons. PATIENTS AND METHODS: This study was a retrospective review of consecutive patients in a 3-year period who underwent US-FNAC performed by endocrine surgeons and radiologists. Medical records, cytology results, and surgical pathology results were collected and analyzed. RESULTS: A total of 576 US-FNAC were performed on 402 patients during the study period. The endocrine surgeons and radiologists performed 299 and 277 US-FNAC, respectively. The FNAC inadequacy rate was 5.3 % for the endocrine surgeons and 9.3 % for the radiologists (p = 0.05). For thyroid cancer, the sensitivity, specificity, and false negatives of the US-FNAC for the endocrine surgeons was 87 %, 98 %, and 3 %, respectively while that for the radiologists was 88 %, 95 %, and 3.5 %, respectively. Patients with thyroid cancer had a shorter time to surgery in the endocrine surgeons' group (mean 15.3 days) compared to the radiologists' group (mean: 53.3 days; p = 0.01). CONCLUSIONS: US-FNAC performed by an experienced endocrine surgeon is accurate and allows efficient surgical management for patients with thyroid cancer.
PubMed-ID: 22526037
http://dx.doi.org/10.1007/s00268-012-1592-2
Simultaneous Medullary and Differentiated Thyroid Cancer: a Population-Level Analysis of an Increasingly Common Entity.
 Ann Surg Oncol, 19(8):2635-42.
Wong RL, Kazaure HS, Roman SA, Sosa JA. 2012.
BACKGROUND: Simultaneous medullary thyroid carcinoma (MTC) and differentiated thyroid carcinoma (DTC) is a rare entity. This is the first population-level analysis of the characteristics and outcomes of simultaneous MTC/DTC. METHODS: In the Surveillance, Epidemiology, and End Results (SEER) database (1988-2008), patients with simultaneous MTC/DTC were retrospectively compared with those with MTC alone using chi(2), ANOVA, log-rank tests, Cox multivariate regression, and Kaplan-Meier analyses. RESULTS: A total of 162 patients had simultaneous MTC/DTC; 1,699 had MTC alone. MTC was diagnosed first in 67.9 % of simultaneous MTC/DTC cases. Simultaneous MTC/DTC increased from 2.7 % of all MTCs in 1988-1997 to 12.3 % in 2003-2008. Compared with MTC alone, simultaneous MTC/DTC had smaller mean MTC tumor size (2.9 vs. 2.2 cm; p = 0.005) and lower rates of MTC extrathyroidal extension (25.4 vs. 16.8 %; p = 0.015) and distant metastases (15.7 vs. 9.3 %; p = 0.032). Patients diagnosed with DTC first had smaller mean MTC tumor sizes (p = 0.01), whereas patients diagnosed with MTC first had tumor sizes similar to those of MTC alone. Compared with MTC alone, patients with simultaneous MTC/DTC were more likely to receive thyroidectomy (84.7 vs. 93.2 %; p = 0.003) and radioisotopes (4.4 vs. 25 %; p < 0.001). On Kaplan-Meier analysis, disease-specific survival rates were higher for simultaneous MTC/DTC than for MTC alone (10-year survival rates 87 vs. 81 %; p = 0.056). CONCLUSIONS: Simultaneous MTC/DTC is diagnosed earlier in tumor development than MTC alone, with a trend toward better prognosis. This entity likely represents a primary tumor with an incidental pathologic finding of a second malignancy. Each malignancy should be treated according to its respective stage and current guidelines.
PubMed-ID: 22526904
http://dx.doi.org/10.1245/s10434-012-2357-8
Role of Ultrasonographic/Clinical Profile, Cytology, and BRAF V600E Mutation Evaluation in Thyroid Nodule Screening for Malignancy: a Prospective Study.
J Clin Endocrinol Metab, 97(7):2354-61.
Rossi M, Buratto M, Bruni S, Filieri C, Tagliati F, Trasforini G, Rossi R, Beccati MD, Degli Uberti EC, Zatelli MC. 2012.
CONTEXT: Ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) is the most reliable nonsurgical test for distinguishing benign from malignant thyroid nodules. However, there is no consensus on which nodules should undergo FNAB. AIMS: The aims of this study were to evaluate the utility of US-guided FNAB in the diagnostic assessment of nodules with or without clinical/US features suggestive for malignancy and to investigate the additional contribution of BRAF V600E mutation analysis in the detection of differentiated thyroid cancer. DESIGN AND METHODS: Thyroid cytoaspirates from 2421 nodules at least 4 mm in diameter were performed in 1856 patients who underwent cytological evaluation and biomolecular analysis. RESULTS: Cytology showed high positive predictive value and specificity for the diagnosis of malignant lesions. BRAF V600E mutation was found in 115 samples, 80 of which were also cytologically diagnosed as papillary thyroid cancer. BRAF mutation analysis significantly enhanced the diagnostic value of cytology, increasing FNAB diagnostic sensitivity for malignant nodules by approximately 28%. Micro PTC (63% of diagnosed papillary thyroid carcinoma) showed a high prevalence of multifocality, extrathyroidal extension, and lymph node metastases, underlining the malignant potential of thyroid microcarcinomas. Each investigated US/clinical characteristic of suspected malignancy correlated with the presence of a thyroid cancer in thyroid nodules with diameter of at least 4 mm. CONCLUSIONS: These data indicate that nodules of at least 4 mm may underlie a thyroid cancer independently of US/clinical characteristics of suspected malignancy, suggesting the need to perform FNAB. The diagnostic sensitivity for thyroid cancer is significantly increased by BRAF V600E mutation analysis, indicating that the screening for BRAF mutation in FNAB samples has a relevant diagnostic potential.
PubMed-ID: 22535974
http://dx.doi.org/10.1210/jc.2011-3494
Prevalence of Upper Aerodigestive Symptoms in Patients Who Underwent Thyroidectomy With and Without the Use of Intraoperative Laryngeal Nerve Monitoring.
Thyroid, 
Silva IC, Netto ID, Vartanian JG, Kowalski LP, Carrara-de-Angelis E. 2012.
Background: Upper aerodigestive symptoms (UADS) have been reported by patients who have had thyroidectomies. This study evaluated the long-term prevalence of UADS after thyroidectomy in patients who did and who did not have intraoperative laryngeal nerve monitoring (IONM). Methods: This was a cross-sectional study of patients with normal vocal fold mobility who had a thyroidectomy. It included patients who did and did not have this surgery with IONM. All patients answered a questionnaire regarding UADS occurring one or more years after thyroidectomy. The questionnaire dealt with UADS relating to voice and swallowing symptoms and sought to quantify their severity. The 208 patients who underwent thyroidectomy without IONM were designated the CG group. The 100 patients who underwent thyroidectomy with IONM were designated the neuromonitored (NMG) group. Results: The proportion of patients in the CG group who reported UADS was 45%; 25.9% of these patients reported voice symptoms, and 33.6% reported swallowing symptoms. The proportion of patients in the NMG group who reported UADS was 39%; 27% of these patients reported voice symptoms, and 22% reported swallowing symptoms. Thus, patients in the CG group had more swallowing symptoms and a greater severity of UADS-related symptoms than patients in the NMG group. Conclusions: In this study, IONM had a favorable effect in terms of decreasing the prevalence and severity of UADS occurring one year or more after thyroidectomy.
PubMed-ID: 22545701
http://dx.doi.org/10.1089/thy.2011-0118
Ultrasonographic Screening for Thyroid Cancer in Siblings of Patients With Apparently Sporadic Papillary Carcinoma.
Thyroid, 
Rosario PW, Mineiro AF, Lacerda RX, Prates BS, Silva LC, Calsolari MR. 2012.
Background: Epidemiological studies have shown a higher risk of thyroid cancer among individuals who have a relative with papillary thyroid cancer (PTC) compared to those without a family history. This study evaluated the prevalence of thyroid cancer among subjects with only one first-degree relative (sibling) with PTC who had no palpable nodules, factors predictive of this malignancy, and the characteristics of tumors discovered during ultrasonographic screening. Methods: A total of 757 siblings of 447 patients with apparently sporadic PTC were examined. Nodules were palpable in 34 subjects (excluded). The 723 individuals without palpable abnormalities were submitted to thyroid ultrasonography and comprised the group of interest. A control group consisting of 241 volunteers without a family history of thyroid cancer matched for gender and age to the study group was also submitted to thyroid ultrasonography. All nodules >/= 5 mm were examined by fine needle aspiration cytology. Subjects with benign cytology were not submitted to surgery; whereas the subjects presenting malignant, suspicious for a malignancy, indeterminate, or inadequate cytology were referred for thyroidectomy. Results: Ultrasonography detected nodule(s) in 303 (41.9%) study subjects. PTC was observed in 5.94% of the 723 subjects studied (8% women and 3.75% men, p 0.017) and in 14.2% of the 303 subjects with non-palpable nodular disease. In the control group, 80 (33.2%) of the volunteers had nodules. PTC was observed in 1.2% of them and in 3.8% of those with nodular disease. In addition, 7.17% of the 447 patients had siblings with PTC detected only by ultrasonography. Multicentricity of the tumor was the main predictor of the presence of malignancy in siblings of patients with PTC. Twenty-two subjects (3% of those screened) had tumors that were not intrathyroid microcarcinomas (whereas all three tumors detected in controls were intrathyroid microcarcinomas). Screening permitted an earlier diagnosis of the disease when compared to siblings with a spontaneous diagnosis. Conclusions: The present results favor ultrasonographic screening of first-degree relatives of patients with apparently sporadic multicentric PTC, especially among women.
PubMed-ID: 22545722
http://dx.doi.org/10.1089/thy.2011-0349
Management of Grave's Disease Is Improved by Total Thyroidectomy.
World J Surg, 36(8):1943-6.
Annerbo M, Stalberg P, Hellman P. 2012.
BACKGROUND: A retrospective analysis was performed on 267 consecutive patients with Graves' disease (GD). The principal aim of this study was to evaluate the risk for recurrence and complications when changing the surgical method from subtotal (ST) to total thyroidectomy (TT). METHODS: Information from 267 consecutive patients operated on for GD between 2000 and 2006 was collected at Uppsala University Hospital (143) and Falun County Hospital (128). There were 229 women and 38 men. Four patients were operated on twice. A total of 40 STs and 229 TTs were performed. Results were compared to those of a previous cohort from the same hospital, with a majority of STs (157/176) performed from 1980 to 1992. RESULTS: The risk for relapse of GD was reduced from 20 to 3.3 % after the shift from ST to TT. In terms of surgical complications, 2.2 % demonstrated permanent vocal cord paralysis and 4.5 % had persistent hypocalcemia, not significant when compared to the previous cohort. In spite of TT, there were four recurrences, all due to remnant thyroid tissue high up at the hyoid bone. Changing the surgical method did not affect postoperative progression of dysthyroid ophthalmopathy (DO, 7.0 vs. 7.5 %). There were no differences in outcome with respect to which hospital the patients had their operation. CONCLUSION: Change from ST to TT dramatically reduced the risk for recurrence of GD without increasing the rate of complications. TT is not more effective than ST in hampering progression of DO as has been advocated by some. Careful surgical dissection up to the hyoid bone is necessary to avoid recurrence.
PubMed-ID: 22547016
http://dx.doi.org/10.1007/s00268-012-1617-x
Reoperative Central Compartment Dissection for Patients With Recurrent/Persistent Papillary Thyroid Cancer: Efficacy, Safety, and the Association of the BRAF Mutation.
Laryngoscope, 122(7):1634-40.
Tufano RP, Bishop J, Wu G. 2012.
OBJECTIVES/HYPOTHESIS: The aims of this study were to present our experience with reoperative central compartment dissection (RCCD) for recurrent/persistent papillary thyroid cancer (PTC), and to explore the association between the BRAF mutation status and the clinicopathologic characteristics and outcomes of a large cohort of PTC patients who have undergone RCCD. STUDY DESIGN: Case series with chart review. METHODS: This is a retrospective study. One hundred twenty consecutive patients between July 2001 and June 2010 who underwent RCCD for recurrent/persistent PTC performed by a single surgeon (r.p.t.) were reviewed. Data reviewed included demographic information; records from previous operations, RCCD, and any other concurrent procedures; pre- and postoperative serum and ionized calcium levels; pre- and postoperative fiberoptic laryngoscopic examination reports; postoperative notes; and pathology reports. V600E mutations in the BRAF gene were detected by performing pyrosequencing for the 107 patients deemed evaluable for the BRAF mutation. RESULTS: The median time to tumor recurrence (TTR) was 36 months (range, 6-791 months). All recurrent laryngeal nerves (RLNs; 161/161) that were at risk were successfully identified. There were seven new findings of abnormal post-RCCD vocal fold (VF) motion that were the result of intentional RLN resection. Among them, six were because of the need for resection of a local recurrence, and one was because of bulky lymph nodes circumferentially involving the RLN. There were no findings of unexpected RLN injury or VF paralysis. Fifteen patients developed hypocalcemia as a result of RCCD that improved with oral calcium and vitamin D supplementation. Among them, 12 cases developed only post-RCCD transient hypocalcemia (</=6 months), and three patients developed permanent hypocalcemia. No patient exhibited central compartment recurrent/persistent PTC in the post-RCCD period based on semiannual high-resolution neck ultrasound examination with a median follow-up of 41.5 months (range, 6-123 months). Eighty (74.8%) of 107 cases demonstrated the BRAF V600E mutation. The presence of the BRAF mutation was significantly associated with a shorter TTR (P = .015) compared with the BRAF mutation-negative group. The BRAF mutation-positive group had a higher incidence of concurrent lateral lymph node metastases (P = .0064) than the BRAF mutation-negative group. CONCLUSIONS: Recurrent/persistent PTC in the central compartment typically harbors the BRAF mutation. The time to central neck recurrence from initial treatment is significantly shorter in the BRAF-positive population of patients compared to the BRAF-negative group, making it more likely that a recurrence will be identified early in the surveillance period. Although we have demonstrated that RCCD can be performed safely and effectively for nodal metastases, there is still risk involved, and this must be carefully weighed by the multidisciplinary team and the patient in optimizing a tailored plan for management.
PubMed-ID: 22549559
http://dx.doi.org/10.1002/lary.23371
MTOR Pathway Overactivation in BRAF Mutated Papillary Thyroid Carcinoma.
J Clin Endocrinol Metab, 97(7):E1139-E1149.
Faustino A, Couto JP, Populo H, Rocha AS, Pardal F, Cameselle-Teijeiro JM, Lopes JM, Sobrinho-Simoes M, Soares P. 2012.
CONTEXT: There are several genetic and molecular evidences suggesting dysregulation of the mammalian target of rapamycin (mTOR) pathway in thyroid neoplasia. Activation of the phosphatidylinositol-3-kinase/AKT pathway by RET/PTC and mutant RAS has already been demonstrated, but no data have been reported for the BRAF(V600E) mutation. OBJECTIVE: The aim of this study was to evaluate the activation pattern of the mTOR pathway in malignant thyroid lesions and whether it may be correlated with known genetic alterations, as well as to explore the mechanisms underlying mTOR pathway activation in these neoplasias. RESULTS: We observed, by immunohistochemical evaluation, an up-regulation/activation of the mTOR pathway proteins in thyroid cancer, particularly in conventional papillary thyroid carcinoma (cPTC). Overactivation of the mTOR signaling was particularly evident in cPTC samples harboring the BRAF(V600E) mutation. Transfection assays with BRAF expression vectors as well as BRAF knockdown by small interfering RNA revealed a positive association between BRAF expression and mTOR pathway activation, which appears to be mediated by pLKB1 Ser428, and emerged as a possible mechanism contributing to the association between BRAF mutation and mTOR pathway up-regulation. When we evaluated the rapamycin in the growth of thyroid cancer cell lines, we detected that cell lines with activating mutations in the MAPK pathway show a higher sensitivity to this drug. CONCLUSIONS: We determined that the AKT/mTOR pathway is particularly overactivated in human cPTC harboring the BRAF(V600E) mutation. Moreover, our results suggest that the mTOR pathway could be a good target to enhance therapy effects in certain types of thyroid carcinoma, namely in those harboring the BRAF(V600E) mutation.
PubMed-ID: 22549934
http://dx.doi.org/10.1210/jc.2011-2748
Radioiodine for Thyroid Cancer--Is Less More?
N Engl J Med, 366(18):1732-3.
Alexander EK, Larsen PR. 2012.
PubMed-ID: 22551133
http://dx.doi.org/10.1056/NEJMe1202172
Ectopic Thyroid Mass in the Heart.
Lancet, 379(9827):1762.
Landeta F, Hoffmeier A, Fuchs M, Scheld H, Maintz D, Stypmann J, Schober O, Kirchhof P, Spieker T, Waltenberger J. 2012.
PubMed-ID: 22559902
http://dx.doi.org/10.1016/S0140-6736(12)60111-1
Histone Deacetylase Inhibition Modulates E-Cadherin Expression and Suppresses Migration and Invasion of Anaplastic Thyroid Cancer Cells.
J Clin Endocrinol Metab, 97(7):E1150-E1159.
Catalano MG, Fortunati N, Pugliese M, Marano F, Ortoleva L, Poli R, Asioli S, Bandino A, Palestini N, Grange C, Bussolati B, Boccuzzi G. 2012.
CONTEXT: Anaplastic thyroid cancer cells are characterized by a mesenchymal phenotype, as revealed by spindle-shaped cells and absent or reduced levels of E-cadherin. Epigenetic silencing is considered one of the leading mechanisms of E-cadherin impairment, which causes the acquisition of the invasive and metastatic phenotype of anaplastic thyroid cancer. OBJECTIVES: In this study we investigated the effects of histone deacetylase inhibition on E-cadherin expression, cell motility, and invasion in anaplastic thyroid cancer cell cultures. DESIGN: Three stabilized cell lines and primary cultures of anaplastic thyroid cancer were treated with various histone deacetylase inhibitors. After treatment, we evaluated histone acetylation by Western blotting and E-cadherin expression by RT-real time PCR. The proper localization of E-cadherin/beta-catenin complex was assessed by immunofluorescence and Western blot. Transcription activity of beta-catenin was measured by luciferase reporter gene and cyclin D1 expression. The effect on cell motility and invasion was studied both in vitro using scratch-wound and transwell invasion assays and in anaplastic thyroid carcinomas tumor xenografts in mice in vivo. RESULTS: Histone deacetylase inhibition induced the E-cadherin expression and the proper membrane localization of the E-cadherin/beta-catenin complex, leading to reduced cancer cell migration and invasion. CONCLUSIONS: We here demonstrate an additional molecular mechanism for the anticancer effect of histone deacetylase inhibition. The antiinvasive effect in addition to the cytotoxic activity of histone deacetylase inhibitors opens up therapeutic perspectives for the anaplastic thyroid tumor that does not respond to conventional therapy.
PubMed-ID: 22563106
http://dx.doi.org/10.1210/jc.2011-2970
Thyroid Cancer Characteristics in the Population Surrounding Three Mile Island.
Laryngoscope, 122(6):1415-21.
Goyal N, Camacho F, Mangano J, Goldenberg D. 2012.
OBJECTIVES/HYPOTHESIS: To determine differences in disease characteristics between the thyroid cancer populations in the area around the Three Mile Island (TMI) nuclear power plant and the rest of the state of Pennsylvania. STUDY DESIGN: Retrospective cross-sectional study. METHODS: Data from the Pennsylvania Cancer Registry from 1985 to 2008 were reviewed and information regarding age at diagnosis, sex, race, residential status, county of residence, thyroid pathology, thyroid surgery, and staging was recorded. Dauphin, Lancaster, and York counties were defined as the TMI area. RESULTS: Records of 26,357 thyroid cancer patients were reviewed, with 2,611 patients within the TMI area. A higher proportion of papillary thyroid cancer (P < .001) and lower proportion of follicular thyroid cancer (P < .001) were noted in the TMI area population. Thyroid cancer cases from the TMI area were found to be more likely to be diagnosed before the age of 65 years (P < .001), be Pennsylvania born (P < .001), be well differentiated (P < .001), be <10 mm in size (P < .001), and be localized without spread (P < .001). Although the TMI area shows a higher incidence of thyroid cancer as compared to the rest of the state, this was not statistically significant. CONCLUSIONS: The TMI population showed a higher proportion of papillary thyroid cancer and less aggressive pathology and earlier diagnosis compared to the rest of Pennsylvania. No statistically significant difference in thyroid cancer incidence was noted. Overall, the study does not show a clear link with more advanced thyroid cancer and proximity to the TMI nuclear reactors.
PubMed-ID: 22565486
http://dx.doi.org/10.1002/lary.23314
Association Between Benign Thyroid and Endocrine Disorders and Subsequent Risk of Thyroid Cancer Among 4.5 Million U.S. Male Veterans.
J Clin Endocrinol Metab, 97(8):2661-9.
Balasubramaniam S, Ron E, Gridley G, Schneider AB, Brenner AV. 2012.
CONTEXT: Risk factors for thyroid cancer (TC) in males are poorly understood. OBJECTIVES, SETTING, AND PARTICIPANTS: Our aim was to evaluate the relationship between history of benign thyroid and endocrine disorders and risk of TC among 4.5 million male veterans admitted to U.S. Veterans Affairs hospitals between July 1, 1969, and September 30, 1996. DESIGN: We conducted a retrospective cohort study based on hospital discharge records with 1053 cases of TC. MAIN OUTCOME MEASURES: We estimated relative risks (RR) and computed 95% confidence intervals (CI) for TC using time-dependent Poisson regression models. To evaluate potential ascertainment bias and/or delayed diagnosis of TC, we also analyzed RR by time between diagnosis of benign disorder and TC (<5 or >/= 5 yr). RESULTS: RR for TC were significantly elevated with many disorders and were often higher less than 5 yr compared with 5 yr or more before TC diagnosis. RR (95% CI) less than 5 yr/at least 5 yr were 67.9 (42.4-108.8)/28.9 (9.2-90.2) for thyroid adenoma, 77.8 (64.5-93.1)/25.9 (17.9-38.0) for nontoxic nodular goiter, 23.9 (13.8-41.3)/12.9 (4.8-34.4) for thyroiditis, 8.8 (6.9-11.3)/6.0 (3.8-9.6) for hypothyroidism, 6.4 (4.4-9.4)/ 2.0 (0.8-4.8) for thyrotoxicosis, and 1.2 (1.0-1.4)/1.1 (0.9-1.5) for diabetes. For some disorders, RR also significantly varied by attained age and race with younger patients and Blacks having higher RR than older patients and Whites. CONCLUSIONS: We found strong associations for a history of thyroid adenoma, nodular goiter, thyroiditis, or hypothyroidism with TC in males allowing for increased surveillance/delayed diagnosis and evidence that some of these associations are modified by age and race.
PubMed-ID: 22569239
http://dx.doi.org/10.1210/jc.2011-2996
The Impact of Distant Metastases at Presentation on Prognosis in Patients Differentiated Carcinoma of the Thyroid Gland.
Thyroid, 
Nixon IJ, Whitcher M, Palmer FL, Shaha AM, Shah JP, Patel S, Ganly I. 2012.
Background Distant metastases at presentation are rare in well differentiated thyroid cancer (WDTC). The objective of this study is to report outcomes for patients presenting with distant metastases managed by thyroidectomy and radioactive iodine therapy. Methods 52 patients with distant metastases from thyroid cancer diagnosed prior to thyroid surgery (n=32) or on post-op RAI scan following thyroid surgery (n=20) were identified from a database of patients with WDTC treated between 1985-2005. The median age was 58 years (range 12-83 years), with a male to female ratio of 3:2. Forty-seven patients (90%) had total thyroidectomy, 2 (4%) thyroid lobectomy , and 3 patients (6%) were found to be unresectable. Distant metastases were classified into pulmonary and extrapulmonary. Overall survival (OS), disease specific survival (DSS) and locoregional recurrence free survival (LRRFS) were calculated by the Kaplan Meier method. Factors predictive of outcome were determined by univariate and multivariate analyses Results 39 patients (75%) were diagnosed with pulmonary metastases alone and 13 (25%) with extrapulmonary metastases. The sites of extrapulmonary metastases were bone in 9, mediastinum in 1, pyriform sinus in 1, skin in 1, and 1 patient had synchronous lung, bone and intracerebral metastases. Following thyroid surgery 47 patients (90%) were treated with RAI alone and 2 patients had external beam radiation in addition to RAI. With a median follow up after surgery of 78.5 months, the 5-year OS and DSS were 65% and 68% respectively. 29 patients (56%) died during follow up, of whom 24 (46%) died of thyroid cancer. 6 patients (12%) developed recurrent disease in the lateral neck and 3 patients (6%) developed recurrence in the thyroid bed. Age over 45yrs, follicular pathology and extrapulmonary metastases were predictive of lower 5yr DSS ( 56% vs 100%, p<0.001; 50% vs 70% , p=0.004 and 46% vs. 75%, p=0.013 respectively). Conclusion Approximately half of patients with WDTC presenting with distant metastases die of disease within 5 years of initial diagnosis despite thyroid surgery and RAI. Age over 45 years, extrapulmonary metastases and follicular pathology were significant predictors of poor outcome.
PubMed-ID: 22582949
http://dx.doi.org/10.1089/thy.2011-0535
Detection of Subcentimeter Metastatic Cervical Lymph Node by 18F-FDG PET/CT in Patients With Well-Differentiated Thyroid Carcinoma and High Serum Thyroglobulin but Negative 131I Whole-Body Scan.
Clin Nucl Med, 37(6):561-7.
Kunawudhi A, Pak-art R, Keelawat S, Tepmongkol S. 2012.
PURPOSE: This study aimed to evaluate the diagnostic value of 18F-FDG PET/CT and identify the best parameter to detect subcentimeter cervical nodal metastasis in patients with a well-differentiated thyroid carcinoma (WDTC), elevated serum thyroglobulin (Tg) levels, but negative findings in the 131I whole-body scan (WBS). MATERIALS AND METHODS: We prospectively studied 30 consecutive patients with WDTC after standard surgery and radioiodine treatment. All patients had serum Tg greater than 10 ng/mL during thyroid hormone withdrawal but negative findings in the therapeutic 131I WBS. One whole-body CT scan and serial whole-body and neck PET scans were performed between 10 and 170 minutes after 18F-FDG injection. Parameters studied were SUVmax, percent change in SUVmax, SUV ratios of lesions to reference organs, and their percent change. Result in the PET/CT scan was correlated with histopathology and follow-up information. Patient-based and lesion-based (subcentimeter cervical lymph nodes) analyses were performed. Outcome of Tg level after lymph node resection was also analyzed. RESULTS: The overall sensitivity, specificity, accuracy, and positive and negative predictive values were 100%, 78%, 93%, 91%, and 100%, respectively. In lesion-based analysis, the differential SUVmax between 2 time points did not provide higher sensitivity than the individual SUVmax at the 60th or 90th minute. A combined SUVmax at the 90th minute greater than 2.75 and a percent change of SUVmax between the 60th and 90th minute greater than -1.1% provides the best diagnostic value with sensitivity, specificity, accuracy, and positive and negative predictive values of 81%, 90%, 83%, 97%, and 56%, respectively. After surgery, patients with completely resected PET-positive nodes without distant metastasis showed reduction of suppressed Tg to less than 2 ng/mL. CONCLUSIONS: Combined SUVmax at the 90th minute and the percent change of SUVmax between the 60th and 90th minute provides the best diagnostic value to differentiate benign from malignant conditions in subcentimeter lymph nodes.
PubMed-ID: 22614187
http://dx.doi.org/10.1097/RLU.0b013e318252d30e
Malignant and Benign Thyroid Nodules After Total Body Irradiation Preceding Hematopoietic Cell Transplantation During Childhood.
Eur J Endocrinol, 167(2):225-33.
Vivanco M, Dalle JH, Alberti C, Lescoeur B, Yakouben K, Carel JC, Baruchel A, Leger J. 2012.
BACKGROUND: The risk of radiation-induced benign and malignant thyroid nodules is well known. OBJECTIVE: The aim of this study was to determine the occurrence of thyroid nodules and carcinomas after fractionated total body irradiation (TBI) preceding hematopoietic stem cell transplantation (HSCT) for malignant hematological disease during childhood. METHODS: We conducted a retrospective university hospital-based observational study. The participants were 76 patients receiving fractionated TBI between 1989 and 2009 as part of the conditioning regimen for HSCT to treat malignant hematological disease, with a median age of 8.2 (5.7-11.4) years, for whom the last ultrasound examination was performed at a median age of 14.2 (11.2-17) years. The main outcome measure was cumulative incidence of thyroid nodules detected by ultrasound scans followed by biopsy if necessary. RESULTS: Thyroid nodules were examined in 21 (28%) patients, six (29%) of whom were diagnosed with thyroid carcinoma at the age of 2.2-18.6 years after TBI. The cumulative incidence of nodule occurrence increased with increasing time from diagnosis. The 10-year cumulative incidence of benign and malignant thyroid nodules was 16% (95% confidence interval (CI) 4-27%) and 8% (95% CI 0-16%) respectively. Seventeen (22%) patients had hypothyroidism (compensated n=12, in five patients it was transient). No significant independent risk factors were identified in the multivariable competing risk model as a function of nodule occurrence. CONCLUSION: Short-term and life-long monitoring, with screening for nodules of the thyroid gland using ultrasound scans, is recommended for survivors subjected to TBI for HSCT during childhood.
PubMed-ID: 22619350
http://dx.doi.org/10.1530/EJE-12-0073
Suspicious Cervical Lymph Nodes Detected After Thyroidectomy for Papillary Thyroid Cancer Usually Remain Stable Over Years in Properly Selected Patients.
J Clin Endocrinol Metab, 97(8):2706-13.
Robenshtok E, Fish S, Bach A, Dominguez JM, Shaha A, Tuttle RM. 2012.
CONTEXT: The risk of loco-regional recurrence in papillary thyroid cancer (PTC) patients ranges from 15-30%. However, the clinical significance of small-volume loco-regional recurrence detected by highly sensitive ultrasonography is unclear. OBJECTIVE: Our objective was to describe the natural history of abnormal cervical lymph nodes (LN) diagnosed after initial treatment. DESIGN: We conducted a retrospective cohort study. PATIENTS: 166 PTC with patients who had at least one abnormal LN outside the thyroid be on ultrasound and selected for active surveillance were included. MAIN OUTCOME MEASURE: LN growth during a period of active surveillance was the primary outcome. RESULTS: Most patients had classical PTC (85%) and an intermediate risk of recurrence (77%). The median LN size at the start of the observation period was 1.3 cm (range, 0.5-2.7 cm) in largest diameter, with all nodes having at least one abnormal sonographic characteristic (70% of patients had LN with at least two abnormal features). In almost all patients, the LN were in the lateral neck, primarily in levels 3 (43%) and 4 (58%). After a median follow-up of 3.5 yr, only 20% (33 of 166) grew at least 3 mm, 9% (15 of 166) grew at least 5 mm, and 14% (23 of 166) resolved. None of the clinical or sonographic features were predictive of LN growth (positive predictive value range = 0.21-0.57). There were no local complications (nerve damage or local invasion) related to the abnormal nodes and no disease-related mortality. CONCLUSIONS: Suspicious cervical LN in the lateral neck usually remain stable for long periods of time in properly selected PTC patients and can be safely followed with serial ultrasounds.
PubMed-ID: 22639292
http://dx.doi.org/10.1210/jc.2012-1553
Thyroidectomy Decreases Snoring and Sleep Apnea Symptoms.
Thyroid, 
Reiher AE, Mazeh H, Schaefer S, Chen H, Sippel RS. 2012.
Background: Patients with goiters often complain of compressive symptoms, which may contribute to symptoms of obstructive sleep apnea. However, the impact of thyroid enlargement on these symptoms is not clear. Therefore we sought to evaluate whether symptoms of sleep apnea resolved after thyroidectomy by using a validated questionnaire. Methods: The Berlin questionnaire, a validated sleep apnea assessment tool, was provided to patients at a single academic institution before and after thyroidectomy. Patients who admitted to symptoms of snoring were asked to complete the questionnaire before and 8 weeks after surgery to assess for improvement in symptoms. The questionnaire uses 3 categories of questions to determine risk of sleep apnea. Two symptom categories must be positive for a patient to be considered "high risk" for sleep apnea. Results: Forty-five patients completed both pre and post-op questionnaires. The average age of patients completing the questionnaire was 53+/-2, and 78% of patients were female. Average BMI was 33.3+/-1.4 kg/m2. Based on their pre-operative questionnaire score 71% of patients were considered to be high risk for obstructive sleep apnea, this decreased to 51% after surgery (p=0.002). Overall scores significantly improved after surgery (mean 2.0 vs. 1.6, p<0.0001). Specifically, patients noted a significant decrease in snoring frequency after surgery (p=0.002), as well as a significant decrease in whether or not their snoring bothered others (p=0.004). The frequency of nodding off during the day also significantly decreased after surgery (p=0.02). Among patients with >/=25% improvement compared with those with <25% improvement in scores, the only significant difference found was a higher pre-op TSH among patients with <25% improvement (p=0.03). No significant difference was found between age, gender, presence of compressive symptoms, gland weight at resection, presence of thyroiditis, or the largest dimension of the gland at resection. Conclusions: Thyroid surgery appears to significantly improve symptoms of obstructive sleep apnea in patients who screened positive for symptoms prior to surgery. Evaluation of patients with obstructive sleep apnea should include evaluation of thyroid disease, as symptoms of sleep apnea may improve with thyroidectomy.
PubMed-ID: 22642308
http://dx.doi.org/10.1089/thy.2011-0527
The Impact of Implementation of the Bethesda System for Reporting Thyroid Cytopathology on the Surgical Treatment of Thyroid Nodules.
Am Surg, 78(6):706-10.
Richmond BK, O'Brien BA, Mangano W, Thompson S, Kemper S. 2012.
Published data suggest that the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) is valuable in directing therapy of thyroid nodules. Literature examining the effect of the BSRTC on management when compared with pre BSRTC is lacking, however. This study evaluates the impact of applying the BSRTC retrospectively to a series of patients who underwent surgery after a fine-needle aspiration biopsy (FNAB) classified using the pre BSRTC system, and investigates how the BSRTC application to the same population would have ultimately affected the management strategy. One hundred patients who had previously undergone both FNAB and thyroidectomy before implementation of the BSRTC were randomly selected. Each FNAB was examined by a single cytopathologist (blinded to both the original interpretation and the surgical pathology findings) and reclassified using the BSRTC. Accuracy of both systems was examined using the final pathology as the true diagnosis. Of 68 FNABs initially classified as indeterminate, 32 (47.1%) were reclassified as benign. There was no significant difference in overall rates of detection of malignancy on final pathology in specimens classified as benign, both pre and post application of the BSRTC (P = 0.70). Application of the BSRTC resulted in a significant percentage of indeterminate specimens being reclassified as benign, presumably due to more standardized criteria for interpretation and reporting. No significant change in detection of malignancy was observed. We conclude that application of the BSRTC may result in lower rates of thyroidectomy, while preserving the same diagnostic accuracy in the detection of thyroid malignancy.
PubMed-ID: 22643269
Scoring System for Predicting Recurrences in Patients With Papillary Thyroid Microcarcinoma.
Eur J Endocrinol , 167(2):267-75.
Buffet C, Golmard JL, Hoang C, Tresallet C, Du Pasquier FL, Fierrard H, Aurengo A, Menegaux F, Leenhardt L. 2012.
CONTEXT: Papillary thyroid microcarcinomas (PMC) defined as tumors </=10 mm in diameter (including pT1a and pT3 according to the latest pTNM classification) have good prognosis, although recurrence is possible. Clinicians are interested in using a scoring system for predicting recurrences. OBJECTIVE: To identify the prognostic factors for recurrence in patients with PMC and to develop a scoring system based on lymph node involvement, multifocality, and sex. To determine the impact of extrathyroidal invasion (ETI) and a threshold value for analyzing multifocality. METHODS: Single-center retrospective study of a cohort of 1669 patients with PMC managed from 1960 to 2007. The Kaplan-Meier survival rate and prognostic factors of events were analyzed using log-rank tests and uni- and multivariate Cox model-based analyses. A scoring system was proposed. RESULTS: Sixty-eight recurrences were observed. Initial lymph node metastases (P=0.0001), multifocality (P=0.05), and male sex (P=0.01) were significantly associated with recurrence, although there was a period effect (after 1990). PMC size was not a significant variable. Our scoring system allows us to separate patients into three risk groups according to their recurrence-free probability. For PMC Nx patients, total foci size of multifocal tumors >20 mm was significantly associated with recurrence (P<0.0001). Radioiodine (RAI) ablation was associated with better outcome only in PMC with ETI. CONCLUSION: Our scoring system classifies recurrence risk. In PMC Nx patients, multifocality is important in planning therapeutic strategies. Recurrence probability of pT3 PMC appears lower if RAI ablation is performed.
PubMed-ID: 22648965
http://dx.doi.org/10.1530/EJE-12-0105
Outcomes and Prognostic Factors of 251 Patients With Minimally Invasive Follicular Thyroid Carcinoma.
Thyroid , 
Sugino K, Kameyama K, Ito K, Nagahama M, Kitagawa W, Shibuya H, Ohkuwa K, Yano Y, Uruno T, Akaishi J, Suzuki A, Masaki C, Ito K. 2012.
Background: Radioiodine ablation after total thyroidectomy is the generally accepted treatment for patients with widely invasive follicular thyroid carcinoma (FTC). The therapeutic strategy for minimally invasive FTC, on the other hand, is still a matter of controversy. The histological diagnosis of minimally invasive FTC is often made after lobectomy. The aim of this study was to determine the factors associated with the development of distant metastases in patients with minimally invasive FTC. Methods: Between 1989 and 2006, 251 patients with minimally invasive FTC underwent initial surgery at our hospital. Their median follow up period was 7.2 years. There were 194 females and 57 males. Their mean age at the time of surgery was 46 years. Distant metastases were diagnosed in 54 patients (21.5%). In 22 of them distant metastases were diagnosed at the time of the initial surgery (M1), and in the other 32 they were diagnosed during the follow-up period. Age at initial surgery, sex, primary tumor size, histological findings (differentiation, extent of vascular and capsular invasion), completion total thyroidectomy and distant metastases at initial surgery were assessed as prognostic factors for distant-metastases-free survival (DMFS) and cause-specific survival (CSS). The Kaplan-Meier method and log rank test were used to analyze time-dependent variables. The Cox proportional hazard model was used to perform the multivariate analyses. Results: Univariate analysis showed that age (45 years or older) and primary tumor size (4 cm or more) were significant prognostic factors related to postoperative distant metastases in the group of 229 patients without distant metastases at time of the initial surgery. The cumulative survival rate was significantly poorer in M1 patients, patients aged 45 years or older, and patients whose primary tumor size was 4 cm or more. Multivariate analyses showed that age was a significant prognostic factor both for DMFS and CSS. Conclusion: Age was the most powerful prognostic factor for patients with minimally invasive follicular thyroid cancer. The prognoses of patients younger than 45 years old were excellent and distant metastases rarely occurred. Routine completion total thyroidectomy and radioiodine ablation is thought unnecessary for these patients.
PubMed-ID: 22671036
http://dx.doi.org/10.1089/thy.2012-0051
One Month Is Sufficient for Urinary Iodine to Return to Its Baseline Value After the Use of Water Soluble Iodinated Contrast Agents in Post-Thyroidectomy Patients Requiring Radioiodine Therapy.
Thyroid, 
Padovani R, Kasamatsu TS, Nakabashi CC, Camacho CP, Andreoni DM, Malouf EZ, Marone MM, Maciel RM, Biscolla RP. 2012.
Background: There is a concern regarding the use of iodinated contrast agents (ICA) for chest and neck computed tomography (CT) to localize metastatases in patients with differentiated thyroid cancer (DTC). This is because the iodine in ICA can compete with 131I and interfere with subsequent whole scans or radioactive iodine treatment. The required period for patients to eliminate the excess of iodine is not clear. Therefore, to know the period for iodine levels to return to baseline after the injection of ICA would permit a more reliable indication of CT for DTC patients. The most widely used marker to assess the plasmatic iodine pool is the urinary iodine (UI) concentration, which can be collected over a period of 24 hours (24U) or as a single spot urinary sample (sU). As 24U collections are more difficult to perform, sU samples are preferable. It has not been established, however, if the measurement of iodine in sU is accurate for situations of excess iodine. Methods: We evaluated 25 patients with DTC who received ICA to perform chest or neck CT. They collected 24U and sU urinary samples before the CT scan and one week and one, two and three months after the test. Urinary iodine (UI) was quantified by a semi-automated colorimetric method. Results: Baseline median UI levels were 21.8 mug/dL for 24U and 26 mug/dL for sU. One week after ICA, UI median levels were very high for all patients, 800 mug/dL. One month after ICA, however, UI median levels return to baseline in all patients, 19.0 mug/dL for 24U and 20 mug/dL for sU. Although the values of median urinary iodine obtained from sU and 24U samples were signicantly different, we observed a significant correlation between samples collected in 24U and sU in all evaluated periods. Conclusion: One month is required for UI to return to its baseline value after the use of ICA and for patients (after total thyroidectomy and radioiodine therapy) to eliminate the excess of iodine. In addition, sU samples, although not statistically similar to 24U values, can be used as a good marker to evaluate patients suspected of contamination with iodine.
PubMed-ID: 22671246
http://dx.doi.org/10.1089/thy.2012-0099
Gasless Video-Assisted Bilateral Thyroidectomy by the Anterior Chest Wall Approach: 4 Years of Experience.
Surg Laparosc Endosc Percutan Tech, 22(3):255-9.
Cai Q, Huang XM, Sun W, Zheng YQ, Liang FY, Han P, Jiang XY. 2012.
Thyroidectomy can be performed in a variety of ways, and gasless video-assisted approaches have recently become more popular. We performed a study of thyroidectomy on 77 patients with bilateral thyroid lesions carried out using a gasless video-assisted unilateral anterior chest wall approach. Seventy-seven patients underwent bilateral thyroidectomy by the gasless video-assisted unilateral anterior chest wall approach, whereas 64 patients underwent conventional surgery during the same time frame and were considered to be the control group. The eligibility criteria for thyroid surgery by gasless video-assisted unilateral anterior chest wall approach were: no previous neck surgical history, no radiotherapy history, a diagnosis of benign thyroid tumor according to preoperative computed tomographic scan, no inflammation-related diseases or thyroid hyperfunction, no lymphadenectasis, and bilateral tumors </= 4 cm in diameter (1 side </= 2 cm, located in the lower part of the thyroid and near the surface of the thyroid). The 2 groups were compared by surgical style, complications, operative time, cosmetic result, and postoperative pain. The 2 groups were matched in terms of age and sex; the scoring for operative procedure (P=0.443), postoperative drainage (P=0.686), and postoperative pain (P=0.294) were not significantly different. The gasless video-assisted group had less bleeding during surgery than the conventional group and had better cosmetic results (P<0.001), but also had longer surgical durations (P=0.003) and higher costs of hospitalization (P<0.001). Neither group had any permanent recurrent laryngeal nerve paralysis or hypocalcemia, nor were there recurrences duration followed up for 21 +/- 10 months. The gasless video-assisted group had 1 case of ecchymoma and 1 case of temporary recurrent laryngeal nerve paralysis, but both recovered within a month. The complication rates in the 2 groups were not significantly different (chi=1.423, P=0.292). The gasless video-assisted thyroidectomy by the unilateral anterior chest wall approach is a safe and feasible way to treat patients with benign bilateral thyroid lesion with good cosmetic results. The gasless video-assisted thyroidectomy is a valid surgical option for selected patients and that its application will grow in the future.
PubMed-ID: 22678323
http://dx.doi.org/10.1097/SLE.0b013e3182508380
Long-Term Surveillance of Papillary Thyroid Cancer Patients Who Do Not Undergo Postoperative Radioiodine Remnant Ablation: Is There a Role for Serum Thyroglobulin Measurement?
J Clin Endocrinol Metab, 97(8):2748-53.
Durante C, Montesano T, Attard M, Torlontano M, Monzani F, Costante G, Meringolo D, Ferdeghini M, Tumino S, Lamartina L, Paciaroni A, Massa M, Giacomelli L, Ronga G, Filetti S. 2012.
CONTEXT: Serum thyroglobulin (Tg) assays are considered fundamental in postoperative surveillance of differentiated thyroid cancer (DTC) patients. However, the postsurgical profile of Tg levels has never been specifically investigated in patients who do not undergo radioiodine remnant ablation (RRA). OBJECTIVES: Our objective was to explore the evolution of Tg levels over time in DTC patients treated with total or near-total thyroidectomy without RRA. DESIGN: We retrospectively analyzed 290 consecutively diagnosed cases of low-risk (American Thyroid Association criteria) DTC treated with thyroidectomy alone and followed yearly with neck ultrasonography and serum Tg assays. We compared final Tg values in this group and a matched group of 495 RRA-positive patients. Temporal trends of serial Tg levels were also analyzed in 78 of the RRA-negative patients monitored with a high-sensitivity immunoradiometric assay. RESULTS: After follow-up of 2.5-22 yr (median 5 yr), final Tg levels were undetectable (<1 ng/ml) in 274 of 290 RRA-negative patients (95%) and 492 of 495 RRA-positive controls (99%). In the subset of 78 RRA-negative patients, undetectable Tg levels (<0.2 ng/ml) were recorded in 60% at the first postoperative evaluation (3-12 months) and in 79% after 5 yr. Tg levels increased in the single patient who experienced disease recurrence during the observation period. CONCLUSION: In most RRA-negative patients, postoperative serum Tg values spontaneously drop to undetectable levels within 5-7 yr after thyroidectomy. Thus, in later phases, Tg assays may be a valuable tool for follow-up even in patients who do not undergo RRA.
PubMed-ID: 22679061
http://dx.doi.org/10.1210/jc.2012-1123
Loss of the Nerve Monitoring Signal During Bilateral Thyroid Surgery.
Br J Surg, 99(8):1089-95.
Dralle H, Sekulla C, Lorenz K, Nguyen TP, Schneider R, Machens A. 2012.
BACKGROUND: This study aimed to assess current use of recurrent laryngeal nerve monitoring (RLNM) for bilateral thyroid surgery in Germany. It explored the willingness of surgeons to change strategy after loss of signal (LOS) on the first side of resection. METHODS: Surgical departments in Germany equipped with nerve monitors were asked to complete a structured questionnaire, specifying the number of thyroidectomies done in 2010, and the frequencies of RLNM, vagal stimulation, and electromyographic (EMG) recording before and after thyroidectomy. They were also asked about the surgical plan for bilateral goitre after LOS on the first side of resection. RESULTS: Based on manufacturers' sales data, 1119 (89.1 per cent) of 1256 surgical departments in Germany were equipped with nerve monitors in 2010. A total of 595 departments (53.2 per cent), accounting for approximately 75 per cent of all thyroidectomies in Germany during that year, returned a completed questionnaire. RLNM was used in 91.7-93.5 per cent of thyroidectomies, with the addition of routine vagal stimulation in 49.3 per cent before, and 73.8 per cent after resection. EMG responses to vagal stimulation were recorded in 54.8 per cent before, and 72.5 per cent after resection. Some 93.5 per cent of surgeons changed the resection plan for the other side in bilateral thyroid surgery after LOS had occurred on the first side. CONCLUSION: RLNM is now the standard of care during thyroidectomy in Germany. After LOS on the first side of resection in bilateral goitre, more than 90 per cent of respondents declared their willingness to change the resection plan for the contralateral side to avoid the risk of bilateral recurrent laryngeal nerve palsy.
PubMed-ID: 22696115
http://dx.doi.org/10.1002/bjs.8831
[Intraoperative Complications of Neck Surgery]
Intraoperative Komplikationen Bei Operationen Im Halsbereich.
Chirurg, 83(7):626-32.
Simon D, Lassau M, Schmidt-Wilcke P, Boucher M. 2012.
Intraoperative complications of neck surgery are uncommon and rarely life-threatening and exact anatomical knowledge and precise dissection are most important for prevention. Anatomical variants (e.g. non-recurrent nerve, extralaryngeal branching) predispose to damage of the recurrent laryngeal nerve. The use of intraoperative neuromonitoring (IONM) can prevent bilateral nerve damage but in cases of accidental nerve damage primary reconstruction can improve vocal cord function. Autotransplantation of parathyroid tissue can reduce the rate of hypoparathyroidism but cannot be postulated as a routine measure. Intraoperative bleeding can usually be well controlled and greater danger for the patient emanates from early postoperative bleeding for which many techniques (clip, ligature, vessel sealing) can be employed for prevention. Lesions of the thoracic duct can be controlled by clip, ligation or stitch. Smaller lesions of the trachea and esophagus can be secured with direct suture or muscle flap plasty. In cases of larger lesions plastic reconstruction or organ replacement can be necessary.
PubMed-ID: 22718222
http://dx.doi.org/10.1007/s00104-011-2210-9
Minimizing Unnecessary Surgery for Thyroid Nodules.
N Engl J Med, 367(8):765-7.
Jameson JL. 2012.
PubMed-ID: 22731671
http://dx.doi.org/10.1056/NEJMe1205893
Preoperative Diagnosis of Benign Thyroid Nodules With Indeterminate Cytology.
N Engl J Med, 367(8):705-15.
Alexander EK, Kennedy GC, Baloch ZW, Cibas ES, Chudova D, Diggans J, Friedman L, Kloos RT, LiVolsi VA, Mandel SJ, Raab SS, Rosai J, Steward DL, Walsh PS, Wilde JI, Zeiger MA, Lanman RB, Haugen BR. 2012.
BACKGROUND: Approximately 15 to 30% of thyroid nodules evaluated by means of fine-needle aspiration are not clearly benign or malignant. Patients with cytologically indeterminate nodules are often referred for diagnostic surgery, though most of these nodules prove to be benign. A novel diagnostic test that measures the expression of 167 genes has shown promise in improving preoperative risk assessment. METHODS: We performed a 19-month, prospective, multicenter validation study involving 49 clinical sites, 3789 patients, and 4812 fine-needle aspirates from thyroid nodules 1 cm or larger that required evaluation. We obtained 577 cytologically indeterminate aspirates, 413 of which had corresponding histopathological specimens from excised lesions. Results of a central, blinded histopathological review served as the reference standard. After inclusion criteria were met, a gene-expression classifier was used to test 265 indeterminate nodules in this analysis, and its performance was assessed. RESULTS: Of the 265 indeterminate nodules, 85 were malignant. The gene-expression classifier correctly identified 78 of the 85 nodules as suspicious (92% sensitivity; 95% confidence interval [CI], 84 to 97), with a specificity of 52% (95% CI, 44 to 59). The negative predictive values for "atypia (or follicular lesion) of undetermined clinical significance," "follicular neoplasm or lesion suspicious for follicular neoplasm," or "suspicious cytologic findings" were 95%, 94%, and 85%, respectively. Analysis of 7 aspirates with false negative results revealed that 6 had a paucity of thyroid follicular cells, suggesting insufficient sampling of the nodule. CONCLUSIONS: These data suggest consideration of a more conservative approach for most patients with thyroid nodules that are cytologically indeterminate on fine-needle aspiration and benign according to gene-expression classifier results. (Funded by Veracyte.).
PubMed-ID: 22731672
http://dx.doi.org/10.1056/NEJMoa1203208
BRAFV600E Mutation and Papillary Thyroid Cancer: Chicken or Egg?
J Clin Endocrinol Metab, 97(7):2295-8.
Xing M. 2012.
PubMed-ID: 22774213
http://dx.doi.org/10.1210/jc.2012-2201
Loss of the Nerve Monitoring Signal During Bilateral Thyroid Surgery (Br J Surg 2012; 99: 1089-1095).
Br J Surg, 99(8):1096.
Mihai R. 2012.
PubMed-ID: 22777802
http://dx.doi.org/10.1002/bjs.8857
The Impact of Benign Gene Expression Classifier Test Results on the Endocrinologist-Patient Decision to Operate on Patients With Thyroid Nodules With Indeterminate FNA Cytopathology.
Thyroid, 
Duick DS, Klopper J, Diggans JC, Friedman L, Kennedy GC, Lanman RB, McIver B. 2012.
Background: Seventy five percent of thyroid nodules with indeterminate fine needle aspiration (FNA) cytology are found to be benign post-operatively. A novel genomic test, the Afirma(R) gene expression classifier (AGEC), has been available for clinical use in the United States since late 2010. In 2010, two modest-sized validation studies showed that the AGEC could identify a benign gene expression signature in indeterminate cytology thyroid FNA samples with negative predictive value greater than 95%. The objective of this study was to evaluate how the AGEC impacted the joint decision of the endocrinologist and patient to operate when FNA cytology was indeterminate but the AGEC reading of the nodule was benign. Methods: In this cross-sectional cohort study, data was contributed retrospectively by 51 endocrinologists at 21 practice sites that had previously obtained >/= 3 benign AGEC readings in >/= 1cm nodules with indeterminate FNA cytology readings. Information regarding demographic data, nodule size and location, decision to operate, surgery type (hemithyroidectomy (HT) or total thyroidectomy (TT)) and reason for recommending surgery was retrospectively collected. Results: Compared to a 74% previous historical rate of surgery for cytologically indeterminate nodules, the operative rate fell to 7.6% during the period that AGEC were obtained in the clinical practices, a highly significant reduction in the decision to operate (p < 0.001). The rate of surgery on cytologically indeterminate nodules that were benign by the AGEC reading did not differ from the historically reported rate of operation on cytologically benign nodules (p=0.41). The four primary reasons reported by the physicians for operating on nodules with a benign AGEC reading, in descending order, were: large nodule size (46.4%), symptomatic nodules (25.0%), rapidly growing nodules (10.7%), or a second suspicious or malignant nodule in the same patient (10.7%). These reasons are concordant with those typically given for operation on cytologically benign nodules. Conclusions: In a substantial group of medical practices, obtaining an AGEC test in patients with cytologically indeterminate nodules was associated with a striking reduction in rate of diagnostic thyroidectomy. Approximately one surgery was avoided for every two AGEC tests run on thyroid FNAs with indeterminate cytology.
PubMed-ID: 22783846
http://dx.doi.org/10.1089/thy.2012-0180
The Additive Clinical Value of 18F-FDG PET/CT in Defining the Recurrence of Disease in Patients With Differentiated Thyroid Cancer Who Have Isolated Increased Antithyroglobulin Antibody Levels.
Clin Nucl Med, 37(8):755-8.
Ozkan E, Soydal C, Araz M, Aras G, Ibis E. 2012.
AIM: The aim of this study was to investigate the additive clinical value of 18F-FDG PET/CT in defining the recurrence of disease in patients with differentiated thyroid cancer (DTC) who have isolated increased antithyroglobulin antibody (TgAb) levels with undetectable thyroglobulin (Tg) levels and negative 131I whole-body scintigraphy (wbs). MATERIALS AND METHODS: Clinical follow-up data of 231 patients with DTC who underwent 18F-FDG PET/CT between June 2006 and March 2011 were evaluated retrospectively. There were a total of 48 patients who underwent 18F-FDG PET/CT for isolated increased serum TgAb levels. When 17 patients who have lymphocytic thyroiditis were excluded, the remaining 31 patients [27 women and 4 men; mean (SD) age, 50.29 (15.2) y] were included in this study. The inclusion criteria were undetectable serum Tg and increased TgAb levels under the condition of thyroid-stimulating hormone greater than 30 IU/mL with negative 131I wbs and absence of pathologic findings in neck ultrasound and thoracic CT if performed. Findings from the 18F-FDG PET/CT were compared with the clinical follow-up data and the results of histopathologic examinations. RESULTS: Results of 18F-FDG PET/CT were negative in 15 and positive in 16 patients. Sixteen FDG-positive sites (15 lymph nodes and 1 bone) were seen in 16 patients who had positive findings in 18F-FDG PET/CT. In the comparison with 18F-FDG PET/CT findings and clinical follow-up data and histopathologic examination results, 4, 12, 2, and 13 patients were false-positive, true-positive, false-negative and true-negative retrospectively. In the receiver operating characteristic analysis, a 5.4 cutoff SUVmax value was calculated with 82% sensitivity and 81% specificity in distinguishing malignant and benign lesions. As a result, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 18F-FDG PET/CT in the detection of recurrent disease were calculated as 75%, 76%, 75%, 86%, and 80%, respectively. CONCLUSIONS: Isolated increased TgAb levels might be a predictor of the recurrent DTC and 18F-FDG PET/CT might be an additive imaging method in detecting the recurrent disease in patients with DTC who have increased TgAb levels with undetectable Tg levels and negative 131I wbs.
PubMed-ID: 22785502
http://dx.doi.org/10.1097/RLU.0b013e31825ae77b
Complications of Central Neck Dissection in Patients With Papillary Thyroid Carcinoma: Results of a Study on 1087 Patients and Review of the Literature.
Thyroid, 22(9):911-7.
Giordano D, Valcavi R, Thompson GB, Pedroni C, Renna L, Gradoni P, Barbieri V. 2012.
BACKGROUND: Prophylactic central neck dissection (CND) has been proposed in the treatment of patients affected by papillary thyroid carcinoma (PTC) with clinically negative neck lymph nodes. The procedure allows pathologic staging of lymph nodes of the central compartment and treatment of the micrometastases. Nevertheless, the morbidity that its routine use adds to the total thyroidectomy must be taken into account. The aim of this study was to characterize the morbidity that CND adds to the total thyroidectomy. METHODS: This was a retrospective study of 1087 patients with PTC and clinically negative neck lymph nodes. Patients were divided into three study groups: Group A, total thyroidectomy; Group B, total thyroidectomy and ipsilateral CND; Group C, total thyroidectomy and bilateral CND. Primary endpoints of the study were evaluated by comparing the rates of transient and permanent recurrent laryngeal nerve (RLN) injury and hypoparathyroidism in the three study groups. RESULTS: Analysis of data showed no significant differences in the rate of transient (Group A: 3.6%, Group B: 3.9%, and Group C: 5.5%; p=0.404) and permanent (Group A: 1%, Group B: 0.5%, and Group C: 2.3%; p=0.099) RLN injury between the three study groups. Both ipsilateral CND and bilateral CND were associated with a higher rate of transient hypoparathyroidism (Group: A 27.7%, Group B: 36.1%, and Group C: 51.9%; p=0.014; odds ratio [OR]: 1.477; 95% confidence interval [CI]: 1.091-2.001; p<0.001; OR: 2.827; 95% CI: 2.065-3.870, respectively). Bilateral CND had a higher rate of permanent hypoparathyroidism (Group A: 6.3%, Group B: 7%, and Group C: 16.2%; p<0.001; OR: 2.860; 95% CI: 1.725-4.743). CONCLUSIONS: The increased rates of transient and permanent hypoparathyroidism in our series suggest a critical review of indications for the routine use of prophylactic CND for PTC. Prophylactic CND ipsilateral to the tumor associated with total thyroidectomy may represent an effective strategy for reducing the rate of permanent hypoparathyroidism. Concomitant completion contralateral paratracheal lymph node neck dissection should be performed in presence of lymph node metastasis on intraoperative frozen-section pathology. This approach limits the use of bilateral CND to patients with intraoperative pathological findings of lymph node metastases.
PubMed-ID: 22827494
http://dx.doi.org/10.1089/thy.2012.0011
Risk of Malignancy in Thyroid Incidentalomas Detected by 18F-Fluorodeoxyglucose Positron Emission Tomography: a Systematic Review.
Thyroid, 22(9):918-25.
Soelberg KK, Bonnema SJ, Brix TH, Hegedus L. 2012.
Background: The expanding use of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) has led to the identification of increasing numbers of patients with an incidentaloma in the thyroid gland. We aimed to review the proportion of incidental thyroid cancers found by (18)F-FDG PET or PET/computed tomography imaging. Methods: Studies evaluating thyroid carcinomas discovered incidentally in patients or healthy volunteers by (18)F-FDG PET were systematically searched in the PubMed database from 2000 to 2011. The main exclusion criteria were known thyroid disease, lack of assigned diagnoses, investigation of diffuse uptake only, or investigation of patients with head and neck cancer, or cancer in the upper part of the thorax. Results: Twenty-two studies met our criteria comprising a total of 125,754 subjects. Of these, 1994 (1.6%) had unexpected focal hypermetabolic activity, while 999 of 48,644 individuals (2.1%) had an unexpected diffuse hypermetabolic activity in the thyroid gland. A diagnosis was assigned in 1051 of the 1994 patients with a focal uptake, 366 of whom (34.8%) had thyroid malignancy. Likewise, a diagnosis was assigned in 168 of 999 patients with a diffuse uptake, 7 of whom (4.4%) had thyroid malignancy. In the eight studies reporting individual maximum standardized uptake values (SUV(max)), the mean SUV(max) was 4.8 (standard deviation [SD] 3.1) and 6.9 (SD 4.7) in benign and malignant lesions, respectively (p<0.001). Conclusions: Incidentally found thyroid nodules, using (18)F-FDG PET, are at high risk of harboring malignancy if uptake is focal. SUV are significantly higher in malignant than in benign nodules. The pronounced inhomogeneity and other shortcomings of the studies are discussed.
PubMed-ID: 22827552
http://dx.doi.org/10.1089/thy.2012.0005
Postradioiodine Treatment Whole-Body Scan in the Era of 18-Fluorodeoxyglucose Positron Emission Tomography for Differentiated Thyroid Carcinoma With Elevated Serum Thyroglobulin Levels.
Thyroid, 22(8):832-8.
Leboulleux S, El B, I, Borget I, Elleuch M, Deandreis D, Al GA, Chougnet C, Bidault F, Mirghani H, Lumbroso J, Hartl D, Baudin E, Schlumberger M. 2012.
BACKGROUND: Patients with differentiated thyroid cancer (DTC) who have a suspicious recurrent or persistent disease based on an elevated serum thyroglobulin (Tg) or Tg antibodies (TgAb) are usually referred for empiric radioiodine ((131)I) administration to localize and treat the disease. The aim of this retrospective monocentric study was to assess the sensitivity of postempiric (131)I whole-body scan (WBS) compared to 18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in such patients who had an initial normal postablation WBS. METHODS: Among 47 consecutive patients with DTC who had a normal postablation WBS and were referred for empiric (131)I administration, 34 patients (12M, 22F; mean age 53 years) underwent FDG PET/CT and form the basis of this report: 23 patients had persistently elevated serum Tg levels, 10 had elevated Tg levels observed during follow-up after they initially became under 1 ng/mL, and 1 had appearance of TgAb during follow-up. Postempiric (131)I WBS and FDG PET/CT were analyzed by independent readers. RESULTS: A total of 75 lesions were found in 23 patients, distributed in 36 organs. Lesions were located in the neck (30), lungs (28), mediastinum (11), and bones (6). The sensitivities for the detection of individual lesions and for the diagnosis of metastatic organs were 88% and 97% for PET/CT and 16% and 22% for WBS, respectively (p<0.01). PET/CT was abnormal in 22 patients, among which 5 also had an abnormal postempiric (131)I WBS. There was only one patient with an abnormal postempiric (131)I WBS and a normal FDG PET/CT. This patient underwent two further (131)I administrations, with the last WBS being normal and the last stimulated Tg level being undetectable. Other patients were either treated with surgery, or classified as radioactive iodine refractory and treated with levothyroxine suppressive therapy or tyrosine kinase inhibitors. CONCLUSION: In patients with suspicious recurrence based on the Tg level after a normal postablation WBS, FDG PET/CT is the preferred scintigraphic method to localize disease rather than postempiric (131)I WBS. Empiric (131)I administration may be used only in patients who do not have a significant FDG uptake.
PubMed-ID: 22853728
http://dx.doi.org/10.1089/thy.2012.0081
Racial Disparities in Voice Outcomes After Thyroid and Parathyroid Surgery.
Surgery, 
Radowsky JS, Helou LB, Howard RS, Solomon NP, Stojadinovic A. 2012.
BACKGROUND: There is evidence that the outcomes of head and neck surgery may differ across racial and ethnic groups. Vocal changes related to the operation are an anticipated risk of thyroidectomy and parathyroidectomy. Race-specific voice outcomes after thyroid and parathyroid operations have not been reported. Therefore, our aim was to examine the potential disparity in voice outcomes between white and black patients after thyroid or parathyroid operations. PATIENTS AND METHODS: Eighty-seven patients (59 white and 28 black) were included in a prospective observational trial. Subjects were evaluated before operation, and 2 weeks, 3 months, and 6 months postoperatively using a comprehensive battery of functional voice assessments of voice characteristics. The association of race with voice outcomes over time was evaluated with generalized linear models. RESULTS: Aside from volume of pathologic specimen (black, 117.5 cm(3) vs white, 43.2 cm(3); P = .004), presence of multinodular goiter (black, 32.1% vs white, 6.8%; P = .004) or Hashimoto's thyroiditis (black, 3.6% vs white, 28.8%; P = .009), there were no differences between racial groups. Blacks were more likely than whites to have negative voice outcomes (odds ratio, 2.6; 95% confidence interval, 1.1-6.2; P = .034] throughout the postoperative period, especially at 6 months (black, 25% vs white, 4%; P = .018). This finding was related principally to divergent scores on the voice-related quality-of-life scale, the Voice Handicap Index. CONCLUSION: We observed greater rates of self-reported, negative voice outcomes among blacks than whites after thyroid or parathyroid operations. The precise mechanism for this disparity has not been described. The observed racial disparity in self-perceived voice impairment in this study merits further investigation.
PubMed-ID: 22862898
http://dx.doi.org/10.1016/j.surg.2012.06.001
Prevention of Complications in Transaxillary Single-Incision Robotic Thyroidectomy.
Thyroid, 
Nam KH, Owen R, Inabnet WB. 2012.
Background: Transaxillary robotic thyroidectomy, developed by the Yonsei University group from Seoul, Korea is a new approach that eliminates the need for a cervical incision. Originally, this technique was performed using a two-incision technique (ipsilateral axilla and anterior chest wall). More recently, the chest wall incision is being eliminated and a less invasive robotic thyroid procedure is being performed through a single axillary incision. Summary: The complexity of this new technique introduces the potential for new complications particularly during the initial learning curve that are not routinely or previously associated with conventional open thyroidectomy. This article will aide surgeons in overcoming the learning curve of transaxillary single-incision robotic thyroidectomy, giving a detailed explanation of the robotic surgical procedure, the possible complications, and complication management. Conclusions: If surgeons have mastery of the multiple steps of the robotic surgical procedure and a good understanding of possible complications and how to prevent them, transaxillary single-incision robotic thyroidectomy can be performed safely and offers numerous advantages over multi-incision robotic thyroidectomy as well as conventional open thyroidectomy.
PubMed-ID: 22866942
http://dx.doi.org/10.1089/thy.2012-0068
Approach to the Patient With Anaplastic Thyroid Carcinoma. 
J Clin Endocrinol Metab, 97(8):2566-72.
Smallridge RC. 2012.
Anaplastic thyroid carcinoma is the least common but most lethal of thyroid cancers. All patients are classified as stage IV, with the primary lesion restricted to the thyroid gland in stage IVA; locoregional lymph nodes may exist in IVA/IVB; and IVC disease is defined by distant metastases. Prognosis is highly dependent on disease extent at presentation, and staging and establishing a plan of care must be accomplished quickly. Although almost all studies are biased due to their retrospective nature, the most important factors associated with longer survival are completeness of surgical resection (achievable in only a minority of patients) and high-dose (>40 Gy) external beam radiotherapy (preferably intensity modulated radiation therapy). Recent reports suggest that a multimodal approach (surgery, radiation, and chemotherapy) is beneficial. Given the high lethality even with apparent local disease, combination systemic therapy (cytotoxics and/or targeted agents) may improve outcomes in stage IVA/IVB patients. Newer, more effective drug combinations are urgently needed for IVC patients who want aggressive therapy. A candid discussion of the prognosis and management options, including palliative care/hospice, should be held with the patient and caregiver as soon as possible after diagnosis to clarify the patient's preference and expectations. Prospective multicenter clinical trials, incorporating molecular analyses of tumors, are required if we are to improve survival in anaplastic thyroid carcinoma.
PubMed-ID: 22869844
http://dx.doi.org/10.1210/jc.2012-1314
Recombinant Human Thyroid Stimulating Hormone-Assisted Radioactive Iodine Remnant Ablation in Thyroid Cancer Patients at Intermediate to High Risk of Recurrence.
Thyroid, 22(10):1007-15.
Hugo J, Robenshtok E, Grewal R, Larson S, Tuttle RM. 2012.
BACKGROUND: Multiple studies have demonstrated successful radioactive iodine remnant ablation (RRA) following preparation with recombinant human thyroid stimulating hormone (rhTSH). Short-term studies in relatively low-risk patients have also suggested that rhTSH-stimulated RRA can have an effective adjuvant therapy function in destroying residual microscopic thyroid cancer cells. However, very few of these studies have included a significant number of intermediate or high-risk patients. The goal of this study was to examine clinical outcomes after rhTSH stimulated RRA in a larger cohort of thyroid cancer patients at higher risk of recurrence and disease-specific mortality. METHODS: A retrospective chart review identified 586 thyroid cancer patients prepared for RRA with either a thyroid hormone withdrawal (THW) (n=321) or rhTSH preparation (n=265). The primary end points included both the best response to initial therapy and the clinical status at final follow-up. Clinical outcomes were compared within each of the American Thyroid Association (ATA) risk groups (low, intermediate, and high) and American Joint Committee on Cancer (AJCC) stages (I-IV) based on the method of preparation for RRA (THW vs. rhTSH). RESULTS: Preparation with rhTSH was more likely to be associated with an excellent response to therapy (39.4% for rhTSH vs. 30% for TWH, p=0.03) and fewer additional therapies (29% for rhTSH vs. 37% for TWH, p=0.05) than THW. However, after a median follow-up period of 9 years, the final clinical outcomes were not significantly different with respect to recurrence rates (1.5% for rhTSH vs. 1.2% for TWH), likelihood of having persistent disease (46% for rhTSH vs. 48% for THW) or likelihood of having no evidence of disease (53% for rhTSH vs. 52% for TWH). Furthermore, clinical outcomes were similar between rhTSH and THW preparation across all ATA risk groups and AJCC stages. CONCLUSIONS: rhTSH preparation for RRA is associated with a small, but statistically significant improvement in an initial response to therapy and similar final clinical outcomes across a wide range of risk of recurrence and risk of disease-specific mortality. These data suggest that rhTSH preparation for RRA can be effectively used in intermediate and high-risk patients without known distant metastases.
PubMed-ID: 22873801
http://dx.doi.org/10.1089/thy.2012.0183
Implantation at Sternocleidomastoid and Chest Wall After Endoscopic Thyroid Carcinoma Surgery.
Surg Laparosc Endosc Percutan Tech, 22(4):e239-e242.
Li S, Zhang F, Zhang Y, Liang Y, Qi X, Yang X, Jiang J. 2012.
Endoscopic thyroidectomy has been widely accepted by surgeons and patients for less postoperative pain, faster postoperative recovery, and excellent cosmetic effect. However, there still existed some limitations. Here, we reported a woman who suffered local implantation metastasis at sternocleidomastoid and chest wall after endoscopic thyroid carcinoma surgery. Although the implantation after endoscopic surgery is uncommon, this case reminds us to use endoscopic surgery for thyroid diseases with caution, especially for thyroid cancer. Following strict endoscopic surgery indications, comprehensive preoperative evaluation, meticulous intraoperative surgical handling, and effective protective measures, the incidence of locoregional implantation or recurrence might be dramatically reduced.
PubMed-ID: 22874712
http://dx.doi.org/10.1097/SLE.0b013e318259f43b
The Prognostic Significance of Nodal Metastases From Papillary Thyroid Carcinoma Can Be Stratified Based on the Size and Number of Metastatic Lymph Nodes, As Well As the Presence of Extranodal Extension ATA Surgical Affairs Committee's Taskforce on Thyroid Cancer Nodal Surgery.
Thyroid, 
Randolph G, Duh QY, Heller KS, LiVolsi VA, Mandel SJ, Steward D, Tufano RP, Tuttle RM. 2012.
Background: Prophylactic dissections have facilitated identification of small volume cervical lymph node metastases in patients with papillary thyroid carcinoma (PTC). Since most staging systems do not stratify risk based on size or number of lymph node metastases, even a single microscopic lymph node metastasis can upstage a patient to an intermediate risk of recurrence in the American Thyroid Association (ATA) system and to an increased risk of death in the American Joint Committee on Cancer (AJCC) staging system (stage III if the metastatic node is in the central neck or stage IVa if the microscopic lymph node metastasis is identified in the lateral neck). Such "microscopic upstaging" may lead to potentially unnecessary or additional treatments. The goal is to determine if specific characteristics of lymph node metastases can be used to stratify risk of recurrence in PTC. Summary: In patients with pathological proven cervical lymph node metastases (pN1), the median risk of loco-regional lymph node recurrence varies markedly by clinical staging, with recurrence rates for patients who are initially clinically N0 (cN0) of 2% vs. rates of recurrence for patients who are initially clinically N positive (cN1) of 22%, Furthermore, the median risk of recurrence in pN1 patients varies markedly by the number of positive nodes, <5 nodes (4%) vs. >5 nodes (19%). Additionally, the presence of extranodal extension was associated with a median risk of recurrence of 24% (range 15% to 32%) and possibly worse disease specific survival. Conclusion: Previously all patients with N1 disease were judged at the same level of risk for recurrance. However, small volume subclinical microscopic N1 disease clearly conveys a much smaller risk of recurrence than large volume, macroscopic clinically apparent nodalmetastases. Armed with this information clinicians will be better able to tailor treatment and follow-up recommendations. Implications of N1 stratification for PTC into small volume microscopic disease vs. clinically apparent macroscopic disease relate to issues of prophylactic neck dissection utility, need for pathologic nodal size description and potential modifications to the AJCC TNM and ATA risk recurrence staging systems.
PubMed-ID: 22881837
http://dx.doi.org/10.1089/thy.2012-0043
Images in Clinical Medicine. Chvostek's and Trousseau's Signs.
N Engl J Med, 367(11):e15.
Jesus JE, Landry A. 2012.
PubMed-ID: 22970971
http://dx.doi.org/10.1056/NEJMicm1110569
Management of Patients With Primary Hyperparathyroidism and Concurrent Thyroid Disease: an Evolving Field.
Ann Surg Oncol, 19(5):1428-9.
Spanheimer PM, Weigel RJ. 2012.
PubMed-ID: 22395994
http://dx.doi.org/10.1245/s10434-012-2286-6
An Intrathyroidal Parathyroid: Thyroid Vein Sampling Prior to Lobectomy.
Am Surg, 78(7):818-9.
Abdo A, Kowdley GC. 2012.
PubMed-ID: 22748545
An Unusual Association of Cerebral Schwannoma, Parathyroid Adenoma, and Papillary Thyroid Carcinoma.
Am Surg, 78(8):E375-E376.
Manchanda C, Nagpal K, Cosgrove JM, Saraiya R. 2012.
PubMed-ID: 22856482

Parathyroids
Meta-Analyses
- None -
Randomized controlled trials
- None -
Other Articles
Cinacalcet (Sensipar) Provides No Measurable Clinical Benefits for Patients With Primary Hyperparathyroidism and May Accelerate Bone Loss With Prolonged Use.
Ann Surg Oncol, 19(5):1466-71.
Norman J, Lopez J, Politz D. 2012.
BACKGROUND: Cinacalcet (Sensipar) has been shown to decrease calcium levels in patients with primary hyperparathyroidism (PHPT); however, few other endpoints have been studied and long-term effects are not known. METHODS: At the discretion of a referring doctor, 70 patients began Cinacalcet as an alternative to surgery for PHPT. Patients were followed as long as the drug was tolerated at which time all underwent parathyroidectomy. RESULTS: Before treatment, serum calcium levels averaged 11.7 +/- 0.5 (range, 11.0-15.1) and PTH averaged 156 +/- 42 (range, 88-815); 93% had two or more classic parathyroid symptoms (average, 5.3; range, 0-9). Cinacalcet was discontinued in 19 patients (26%) within 4 months because of nausea/vomiting. The remainder (n = 51) were treated from 8 to 28 months. Calcium levels decreased in all patients but remained variable. PTH levels decreased in 80% of patients but always remained elevated. Only 3 (6%) had symptom relief (p = 0.8), whereas 11 (21.6%) felt worse (p < 0.05). Twenty-three patients took Cinacalcet for >1.5 years, 14 of which showed significant (>1 SD) decreases in bone density (p < 0.05), and none had increases in bone density. All had curative outpatient parathyroid surgery followed by partial or complete resolution of symptoms within 3 months in 88% (p < 0.001). CONCLUSIONS: Cinacalcet reduces serum calcium but is not tolerated by many patients. Cinacalcet does not provide symptom relief of PHPT and more commonly increases subjective symptoms. Prolonged use is associated with continued bone loss in some patients, possibly due to persistent elevated PTH levels. With very few exceptions, pHPT can be cured via a quick outpatient operation, which remains the treatment of choice.
PubMed-ID: 21922336
http://dx.doi.org/10.1245/s10434-011-2065-9
Re: The Necessity and Reliability of Intraoperative Parathyroid Hormone (PTH) Testing in Patients With Mild Hyperparathyroidism and PTH Levels in the Normal Range.
World J Surg, 36(2):483-5.
Agarwal S, Agarwal A, Chand G. 2012.
PubMed-ID: 21947460
http://dx.doi.org/10.1007/s00268-011-1281-6
Parathyroid Four-Dimensional Computed Tomography: Evaluation of Radiation Dose Exposure During Preoperative Localization of Parathyroid Tumors in Primary Hyperparathyroidism.
World J Surg, 36(6):1335-9.
Mahajan A, Starker LF, Ghita M, Udelsman R, Brink JA, Carling T. 2012.
BACKGROUND: Parathyroid four-dimensional computed tomography (4DCT) provides greater sensitivity than sestamibi with single photon emission CT (SPECT, or SeS) for preoperative localization of parathyroid tumors in patients with primary hyperparathyroidism (PHPT). The radiation dose imparted to the patient during preoperative parathyroid imaging, however, has not been analyzed. METHODS: Patients with biochemically unequivocal PHPT referred for minimally invasive parathyroidectomy underwent 4DCT or SeS. 4DCT was performed using a 64 detector row CT scanner, and SeS used a standardized protocol of 20 mCi of technetium-99m followed by planar and SPECT imaging. The CT radiation dose was estimated using the Imaging Performance Assessment of CT Scanners (ImPACT) calculator, and the SeS dose was estimated using the US Nuclear Regulatory Commission Regulation (NUREG) method. RESULTS: The calculated effective doses of 4DCT and SeS were 10.4 and 7.8 mSv, respectively, in contrast to an estimated annual background radiation exposure of approximately 3 mSv. The dose to the thyroid with 4DCT, however, was about 57 times higher (92.0 vs. 1.6 mGy) than that with SeS. Based on age- and sex-dependent risk factors, the calculated risk of 4DCT-related thyroid cancer developing in a 20 year old woman was 1,040/million (i.e., about 0.1%). CONCLUSIONS: 4DCT, a superior preoperative imaging modality for locating parathyroid tumors, imparts a significantly higher thyroid radiation dose than SeS. Given the enhanced risk of thyroid cancer in individuals with radiation exposure at a young age, 4DCT should be used judiciously in young PHPT patients.
PubMed-ID: 22146947
http://dx.doi.org/10.1007/s00268-011-1365-3
Evaluation of Selected Cognitive Functions Before and After Surgery for Primary Hyperparathyroidism.
Langenbecks Arch Surg, 397(5):825-31.
Babinska D, Barczynski M, Stefaniak T, Oseka T, Babinska A, Babinski D, Sworczak K, Lachinski AJ, Nowak W, Sledzinski Z. 2012.
BACKGROUND AND AIMS: Cognitive functions have been reported to be impaired in patient with primary hyperparathyroidism (pHPT). The aim of this psychological study was to evaluate cognitive disturbances in pHPT in relation to serum calcium levels before and after surgery. PATIENTS AND METHODS: A prospective, case-control study with 1-year follow-up of 35 pHPT patients versus 35 matched controls was undertaken. All patients were tested before surgery and at 12-18 months following surgery with a battery of selected cognitive function psychological tools: Benton Visual Retention Test (BVRT), Wisconsin Card Sorting Test (WCST), Memory Verbal Learning Test (DCS), The Rey's Auditory Verbal Learning Test (RAVLT), Trail Making Test A & B, Verbal Fluency Test, and Beck Depression Inventory. In addition to psychological testing, serum calcium, parathyroid hormone and phosphate levels were evaluated. RESULTS: The following cognitive functions of pHPT patients versus controls were deteriorated before surgery: impaired concentration, decreased nonverbal learning process, difficulties in using direct memory, verbal fluency and visual constructive abilities. However, no correlation was found between serum calcium levels and the results of neuropsychological tests. In longitudinal comparison of pHPT patients before and 1 year after surgery, there was a significant improvement in visual memory, visual-constructive abilities and direct memory. CONCLUSIONS: pHPT patients have significantly decreased concentration level, nonverbal learning process, access to verbal resources and constructional and visual memory ability. Thus, neuropsychological testing may be useful in the decision making for early surgery in patients with mild asymptomatic disease in order to avoid further deterioration of cognitive functions.
PubMed-ID: 22160326
http://dx.doi.org/10.1007/s00423-011-0885-5
A Predictive Model of Suitability for Minimally Invasive Parathyroid Surgery in the Treatment of Primary Hyperparathyroidism [Corrected].
World J Surg, 36(5):1175-81.
Kavanagh DO, Fitzpatrick P, Myers E, Kennelly R, Skehan SJ, Gibney RG, Hill AD, Evoy D, McDermott EW. 2012.
BACKGROUND: Improved preoperative localizing studies have facilitated minimally invasive approaches in the treatment of primary hyperparathyroidism (PHPT). Success depends on the ability to reliably select patients who have PHPT due to single-gland disease. We propose a model encompassing preoperative clinical, biochemical, and imaging studies to predict a patient's suitability for minimally invasive surgery. METHODS: For the purposes of the present study, 180 consecutive patients were included for analysis. A 5-variable model based on preoperative ionized serum calcium (>1.4 mmol/l), intact parathyroid hormone level (>/= 2 times the upper limit of normal), positive sestamibi scan for a single affected gland, positive ultrasound scan for a single gland, and concordance between the two imaging modalities for single-gland disease at a similar location was employed, where a score of 1 was allocated for each variable present. RESULTS: Of the 180 patients, 62 (34%) underwent bilateral exploration, 63 (36%) underwent unilateral exploration, and 55 (30%) underwent minimally invasive parathyroidectomy. The results showed that 92% had single-gland disease, 3% had double adenomas, and 5% had hyperplasia. Biochemical cure was achieved in 98.9%. Mean follow-up was 153 days (range: 80-342 days). With the predictive scoring model, a score of >/= 3 had a positive predictive value of 100% for single-gland disease. CONCLUSIONS: A scoring model encompassing preoperative biochemical and imaging data can be successfully employed to predict suitability for minimally invasive surgery in the majority of patients with single-gland disease.
PubMed-ID: 22170475
http://dx.doi.org/10.1007/s00268-011-1377-z
The Additional Value of Intraoperative Parathyroid Hormone Assessment Is Marginal in Patients With Nonfamilial Primary Hyperparathyroidism: a Prospective Cohort Study.
Am J Surg, 204(1):1-6.
Twigt BA, van DT, Vollebregt AM, Kortlandt W, Vriens MR, Borel Rinkes IH. 2012.
BACKGROUND: The success of minimally invasive parathyroidectomy is attributed to evolving preoperative imaging techniques and intraoperative parathyroid hormone (IOPTH) measurement. The additional value of IOPTH measurement in patients undergoing surgery for primary hyperparathyroidism (pHPT) was evaluated. METHODS: Between 1999 and 2010 there were 119 patients who underwent surgery for pHPT at our institutions. In all patients, preoperative imaging was performed and IOPTH samples were collected prospectively but the results were not disclosed during surgery. RESULTS: Postoperative calcium level normalized in 114 patients (96%). The 5 surgical failures represented the maximum yield of IOPTH sampling. Three of these patients would have been identified intraoperatively by an inadequate IOPTH decrease, whereas IOPTH decreased inaccurately in the other 2 patients. In addition, in 1 of these 3 patients no abnormal gland was found during minimally invasive parathyroidectomy and subsequent conventional neck exploration. Therefore, only 2 reoperations would have been prevented (1.7%). CONCLUSIONS: IOPTH would have changed the outcome in 2 patients, increasing the biochemical cure rate from 96% to 98%. We believe that although it can be helpful in certain cases, it may not be necessary routinely in patients treated for pHPT.
PubMed-ID: 22192616
http://dx.doi.org/10.1016/j.amjsurg.2011.07.017
Does the Final Intraoperative PTH Level Really Have to Fall into the Normal Range to Signify Cure?
Ann Surg Oncol, 19(6):1862-7.
Reiher AE, Schaefer S, Chen H, Sippel RS. 2012.
BACKGROUND: Intraoperative parathyroid hormone (IOPTH) helps shorten the duration of surgery and increase the likelihood of surgical cure. Although general consensus agrees that the IOPTH should fall by 50%, there is much debate as to whether the IOPTH needs to fall into the normal range. METHODS: We retrospectively reviewed a prospective database of patients undergoing surgery for treatment of primary hyperparathyroidism. We included all patients with an IOPTH that fell by >50% by 10 or 15 min, but that did not fall into the normal range (parathyroid hormone remained >/= 60 pg/ml). We excluded patients who had undergone prior neck surgery or had known multiple endocrine neoplasia 1 or 2. RESULTS: A total of 1,231 patients underwent a parathyroidectomy, 155 of whom met the study's inclusion/exclusion criteria (12.6%). A total of 117 patients had an IOPTH fall by 50% by 10 min, and 38 patients' IOPTH fell by 50% by 15 min. Overall surgical cure rate was 98.7%. One patient from the 10-minute group and one patient from the 15-minute group had persistent disease on follow-up. One patient in the 15-minute group had recurrent disease. With a mean +/- SEM 18.1 +/- 2.1 months' follow-up, the recurrence rate in this cohort was 0.6%. The average calcium at last follow-up was 9.4 +/- 0.0 mg/dl. CONCLUSIONS: Allowing the IOPTH to fall by 50% by 15 min, regardless of whether the IOPTH falls into the normal range, results in a high success rate when performed by experienced surgeons. This helps reduce intraoperative time used waiting for additional parathyroid hormone levels and the risks associated with unnecessary bilateral neck exploration.
PubMed-ID: 22203183
http://dx.doi.org/10.1245/s10434-011-2192-3
Thoracoscopic Removal of Mediastinal Parathyroid Lesions: Selection of Surgical Approach and Pitfalls of Preoperative and Intraoperative Localization.
World J Surg, 36(6):1327-34.
Iihara M, Suzuki R, Kawamata A, Horiuchi K, Okamoto T. 2012.
BACKGROUND: Thoracoscopic surgery has replaced conventional sternotomy or thoracotomy for resection of mediastinal parathyroid lesions. We review our experience with this type of surgery with reference to selection of the appropriate approach and the pitfalls of lesion localization before and during surgery. METHODS: During a 14-year period, we treated 14 patients with hyperparathyroidism, in whom a mediastinal lesion had been localized preoperatively by sestamibi scan. Primary hyperparathyroidism was present in 12 patients (single adenoma in 11, associated with MEN 1 in one) and secondary hyperparathyroidism in 2. Thoracoscopic procedures were performed by the three-port method. RESULTS: The thoracoscopic procedure was successful in eight patients who were shown preoperatively to have a deep-seated (5 anterior, 3 middle) mediastinal lesions. Intraoperative visual confirmation of parathyroid adenoma was difficult only in a 19-year-old patient with a tumor embedded in the thymus, necessitating partial thymectomy. One of the eight mediastinal lesions resected thoracoscopically was a sestamibi-positive thymoma. Secondary hyperparathyroidism recurred 4 years after thoracoscopic mediastinal parathyroidectomy in one patient, necessitating additional thoracoscopic removal of this supernumerary lesion. However, seven patients with mediastinal parathyroid lesions localized at the aortic arch or upper region were treated successfully via a cervical approach. None of the patients suffered any surgical complications. CONCLUSIONS: Thoracoscopic surgery is safe and feasible for resection of deep mediastinal parathyroid lesions. Such lesions localized preoperatively at the aortic arch or upper region can be treated via a cervical approach. Preoperative sestamibi scan can sometimes give a false-positive result in cases of concurrent thymoma.
PubMed-ID: 22205108
http://dx.doi.org/10.1007/s00268-011-1404-0
A Comparison of Outcomes for Younger and Older Adult Patients Undergoing Surgery for Primary Hyperparathyroidism.
Ann Surg Oncol, 19(6):1897-901.
Kandil E, Majid DS, Carson KA, Tufano RP. 2012.
BACKGROUND: In adolescents and young adults, primary hyperparathyroidism (PHPT) is an uncommon diagnosis. We compared the clinical characteristics of these patients to those of older adult patients with PHPT. We hypothesized that PHPT in adolescents and young adults is more often caused by single-gland disease and is amenable to minimally invasive parathyroidectomy (MIP). METHODS: We retrospectively reviewed the medical records of 452 consecutive patients who had surgery for PHPT. Patients ranged in age from 13 to 94 years and were dichotomized into younger (age <30 years, n = 17, 3.8%) and older (age >/= 30 years, n = 435, 96.2%) patients. Continuous baseline and intraoperative and postoperative measures were not normally distributed and were summarized with medians and interquartile ranges (IQRs). Groups were compared using Wilcoxon rank sum test or Fisher exact test, and significance was set at P < .05. RESULTS: Median [IQR] age was 24 [23-27] years for the younger group and 58 [51-66] years for the older group. Though not statistically significant, a smaller proportion of the younger patients compared with the older patients had a positive (99m)Tc-sestamibi scan (71%; 95% confidence interval [95% CI] = 44-90% vs. 83%; 95% CI = 79-86%) and showed a suspected parathyroid adenoma on ultrasound (65%; 95% CI = 38-86% vs. 80%; 95% CI = 76-83%). The younger and older age groups did not significantly differ on preoperative serum PTH levels (median [IQR]: 111 [76-145] pg/ml vs 110 [84-152] pg/ml; P = .73 respectively). The younger group had higher serum calcium levels (11.6 [11.1-12.2] mg/dl) compared with the older group (11.1 [10.7-11.5] mg/dl; P = .01). MIP was performed less frequently on the younger patients (70.6%) compared with older patients (88.7%; P = 0.04). Though the incidence of a single adenoma was somewhat more frequent in older patients (90%; 95% CI = 87-93%) than in younger patients (82%; 95% CI = 57-96%) it was the most frequent cause of PHPT in the younger patients. The younger and older groups did not significantly differ on percent drop from baseline for intraoperative PTH monitoring (81.7 vs 79.3%; P = .46), respectively. CONCLUSIONS: Younger patients with PHPT present with significantly higher serum calcium levels than older patients. However, younger patients are less likely to localize abnormal parathyroid glands on sestamibi or ultrasound. Though younger patients appear to have a higher incidence of hyperplasia compared with older patients, single gland disease is still the overall most frequent cause. Our data suggest that MIP should be more frequently considered in younger patients because of the high incidence of single gland disease.
PubMed-ID: 22207049
http://dx.doi.org/10.1245/s10434-011-2185-2
Abandoning Unilateral Parathyroidectomy: Why We Reversed Our Position After 15,000 Parathyroid Operations.
J Am Coll Surg, 214(3):260-9.
Norman J, Lopez J, Politz D. 2012.
BACKGROUND: Our group championed the techniques and benefits of unilateral parathyroidectomy. As our experience has matured, it seems this limited operation might be appropriate only occasionally. METHODS: A single surgical group's experience with 15,000 parathyroidectomies examined the ongoing differences between unilateral and bilateral techniques for 10-year failure/recurrence, multigland removal, operative times, and length of stay. RESULTS: With limited experience, 100% of operations were bilateral, decreasing to 32% by the 500(th) operation (p < 0.001), and long-term failure rates increased to 6%. Failures were 11 times more likely for unilateral explorations (p < 0.001 vs bilateral), causing gradual increases in bilateral explorations to 97% at the 14,000(th) operation (p < 0.001). Ten-year cure rates are unchanged for bilateral operations, and unilateral operations show continued slow recurrence rates of 5% (p < 0.001). Removal of more than one gland occurred 16 times more frequently when 4 glands were analyzed (p < 0.001), increasing cure rates to the current 99.4% (p < 0.001). Of 1,060 reoperations performed for failure at another institution, intraoperative parathyroid hormone levels fell >50% in 22% of patients, yet a second adenoma was subsequently found. Operative times decreased with experience; bilateral operations taking only 5.9 minutes longer on average (22.3 vs 16.4 minutes; p < 0.001), which is 25 minutes less than unilateral at the 500(th) operation (p < 0.001). By the 1,000(th) operation, incision size (2.5 +/- 0.2 cm), anesthesia, and hospital stay (1.6 hours) were identical for unilateral and bilateral procedures. CONCLUSIONS: Regardless of surgical adjuncts (scanning, intraoperative parathyroid hormone), unilateral parathyroidectomy will carry a 1-year failure rate of 3% to 5% and a 10-year recurrence rate of 4% to 6%. Allowing rapid analysis of all 4 glands through the same 1-inch incision has caused us to all but abandon unilateral parathyroidectomy.
PubMed-ID: 22265807
http://dx.doi.org/10.1016/j.jamcollsurg.2011.12.007
Preoperative Serum Osteocalcin May Predict Postoperative Elevated Parathyroid Hormone in Patients With Primary Hyperparathyroidism.
World J Surg, 36(6):1320-6.
Rianon N, Alex G, Callender G, Jimenez C, Hu M, Grubbs E, Moreno M, Wathoo C, Petak S, Perrier N. 2012.
BACKGROUND: Persistent postoperative elevation of parathyroid hormone (POePTH) following successful parathyroidectomy for primary hyperparathyroidism (PHPT) is presumed to result from bone remineralization. Predicting which patients may need treatment is difficult. This study investigated whether preoperative serum osteocalcin (OC), a bone turnover marker involved in mineralization, can predict POePTH. METHODS: A total of 198 patients (155 women and 43 men) with parathyroidectomy from November 2007 to October 2009 in MD Anderson Cancer Center, Houston, TX, USA, were included in our analysis. Separate multivariate regression models determined associations between preoperative OC and POePTH at 6 and 12 months postoperatively. Regression models were adjusted for demographics (age, gender, race, height, weight, BMI), preoperative BMD and bisphosphonate use, adenoma weight, serum levels of PTH, calcium, vitamin D, creatinine, and phosphate. Patients with baseline GFR <60 ml/min/1.73 m(2) and postoperative serum calcium >10.14 mg/dl at 6 and 12 months were excluded. RESULTS: Patients' mean age (+/-SD) was 60 (+/-14) years. POePTH (>80 pg/ml) occurred in 13 and 12% patients at 6 and 12 months, respectively. Preoperative serum creatinine and bisphosphonate use were positively associated with POePTH (p < 0.05) both at 6 and 12 months. Preoperative OC was predictive of POePTH (p < 0.05) at 6 months (beta 0.35; 95% confidence interval (CI), 0.11-0.58) and at 12 months (beta 0.79; 95% CI, 0.27-1.31). CONCLUSIONS: Preoperative OC may help to predict risk of POePTH in patients with PHPT. Research with longer follow-up in patients with no known baseline chronic kidney disease stratified by high versus normal preoperative serum creatinine is recommended.
PubMed-ID: 22278606
http://dx.doi.org/10.1007/s00268-012-1432-4
Preoperative Localizing Studies for Initial Parathyroidectomy in MEN1 Syndrome: Is There Any Benefit?
World J Surg, 36(6):1368-74.
Nilubol N, Weinstein L, Simonds WF, Jensen RT, Phan GQ, Hughes MS, Libutti SK, Marx S, Kebebew E. 2012.
BACKGROUND: The objective of the present study was to evaluate the utility of preoperative localizing studies in patients with MEN1 undergoing initial bilateral neck exploration (BNE) and parathyroidectomy for pHPT. METHODS: We performed a retrospective analysis of patients diagnosed with MEN1 who underwent initial parathyroidectomy between December 1993 and December 2010. Results of preoperative localizing studies were compared with intraoperative findings and outcome. RESULTS: Sixty patients with MEN1 (32 females and 28 males) underwent initial subtotal parathyroidectomy. The median age at the time of surgery was 33 years (range: 13-78 years). Fifty-three patients had one or more positive localizing study results. Neck ultrasonography, sestamibi scan, parathyroid protocol computed tomography scan, and neck and mediastinum magnetic resonance imaging were performed in 93, 91, 32, and 19% of patients, respectively. Fifty-three patients (88%) had cervical thymectomy. Twenty patients had 24 ectopic parathyroid glands; 18 glands were in the thymus (75%). Preoperative localizing studies identified 9 of 24 ectopic parathyroid glands (38%), including 4 ectopic glands outside the thymus in 4 patients (7%); 3 were detected by ultrasonography. There were no supernumerary glands identified on preoperative localizing studies. CONCLUSIONS: In patients with MEN1, preoperative localizing studies identified a subset of ectopic glands (38%). Preoperative localizing studies may alter the operative approach in 7% of patients. Ultrasonography can detect most ectopic parathyroid glands outside thymus. This suggests that routine preoperative localizing studies to identify ectopic and supernumerary enlarged parathyroid glands is not useful in the majority of patients with MEN1 undergoing bilateral neck exploration and subtotal parathyroidectomy with cervical thymectomy.
PubMed-ID: 22350475
http://dx.doi.org/10.1007/s00268-012-1451-1
Thyroid Cancer Detection With Dual-Isotope Parathyroid Scintigraphy in Primary Hyperparathyroidism.
Ann Surg Oncol, 19(5):1446-52.
Onkendi EO, Richards ML, Thompson GB, Farley DR, Peller PJ, Grant CS. 2012.
BACKGROUND: Thyroid cancer cells have been shown to take up (99m)Tc-sestamibi. The role for (99m)Tc-sestamibi scintigraphy (Tc-MIBI) in the diagnosis of thyroid cancer in patients with primary hyperparathyroidism (PHPT) is unclear. Our aim was to determine whether dual-isotope parathyroid scintigraphy is useful in identifying thyroid cancer. METHODS: A prospective database of 3,187 patients who underwent neck exploration for PHPT was reviewed to identify patients who had concurrent thyroid resection. Patients with benign and malignant thyroid disease were comparatively analyzed. RESULTS: A total of 470 patients underwent both thyroidectomy and parathyroidectomy (reoperations in 21%). Benign disease (n = 391, 83%) was more common than malignancy [papillary thyroid cancer (n = 75) and medullary thyroid cancer (n = 5); 1 had both]. Dual-isotope scintigraphy obtained in 374 patients (80%) had a sensitivity of 67% and a positive predictive value of 66% for parathyroid adenoma localization in these patients with thyroid disease. False-positive scintigraphy occurred in 22% with benign and 45% with malignant thyroid disease (P = 0.002). On Tc-MIBI imaging, 54 (86%) of 63 patients with malignancy had hot nodules, compared to 248 (81%) of 308 patients with benign disease (P = 0.49). On I-123 imaging, 34 (54%) of 63 patients with malignancy had cold nodules, compared to 42 (14%) of 304 patients with benign disease (P < 0.001). A dual-isotype phenotype of both Tc-MIBI-Hot and I-123-Cold had sensitivity 52%, specificity 88%, positive predictive value 47%, and negative predictive value 90% for detecting a thyroid malignancy. CONCLUSIONS: A Tc-MIBI-Hot/I-123-Cold phenotype is very specific for detecting thyroid malignancy. Patients with this imaging phenotype should strongly be considered for preoperative ultrasound-guided biopsy. Patients found intraoperatively to have false-positive parathyroid scintigraphy should be evaluated for thyroid cancer.
PubMed-ID: 22395991
http://dx.doi.org/10.1245/s10434-012-2282-x
Management of Patients With Primary Hyperparathyroidism and Concurrent Thyroid Disease: an Evolving Field.
Ann Surg Oncol, 19(5):1428-9.
Spanheimer PM, Weigel RJ. 2012.
PubMed-ID: 22395994
http://dx.doi.org/10.1245/s10434-012-2286-6
Postoperative Hungry Bone Syndrome in Patients With Secondary Hyperparathyroidism of Renal Origin.
World J Surg, 36(6):1314-9.
Goldfarb M, Gondek SS, Lim SM, Farra JC, Nose V, Lew JI. 2012.
BACKGROUND: Hungry bone syndrome (HBS) is a postoperative condition of severe hypocalcemia that can be seen in patients who have undergone parathyroidectomy (PTX) for secondary hyperparathyroidism (2HPT) of renal origin. This study examines HBS in patients after PTX for 2HPT. METHODS: Prospectively collected data was retrospectively reviewed in patients who underwent PTX for 2HPT of renal origin at a single institution. HBS was defined as the need for additional days of hospitalization or readmission for intravenous calcium supplementation due to clinical symptoms of hypocalcemia, including tingling, muscle spasms, and bone pain and/or immediate postoperative low serum calcium </=7.5 mg/dl. RESULTS: Of 79 patients who underwent PTX for 2HPT, 27.8% (n = 22) experienced HBS. Young age (</=45 years, p = 0.02) was the only preoperative variable that predicted HBS. Most patients developed HBS within 18 h after surgery and required a prolonged hospital stay (19/22) compared to those requiring hospital readmission within the first 7 days (3/22). Initial postoperative serum calcium levels within 18 h of surgery were significantly lower in those patients who developed HBS (7.1 vs. 8.3 mg/dl, p = 0.001), and those patients also had a greater absolute decrease in serum calcium (2.8 vs. 3.5 mg/dl, p = 0.04). CONCLUSION: HBS develops in a significant proportion of patients generally within the first 18 h after subtotal PTX for 2HPT. The only identifiable preoperative risk factor for HBS was young age. Additionally, low initial calcium levels and greater absolute decrease in serum calcium may help identify those patients that will develop HBS requiring judicious calcium supplementation.
PubMed-ID: 22399154
http://dx.doi.org/10.1007/s00268-012-1560-x
Effect of Renal Function on Skeletal Health in Primary Hyperparathyroidism.
J Clin Endocrinol Metab, 97(5):1501-7.
Walker MD, Dempster DW, McMahon DJ, Udesky J, Shane E, Bilezikian JP, Silverberg SJ. 2012.
CONTEXT: Current guidelines recommend parathyroidectomy in patients with primary hyperparathyroidism (PHPT) who have an estimated glomerular filtration rate (eGFR) less than 60 ml/min per 1.73 m(2). It is unclear, however, whether values below this threshold of renal impairment affect bone and mineral metabolism in PHPT. OBJECTIVE: The purpose of this study was to assess the effect of renal function on skeletal health in PHPT. DESIGN: This is a retrospective analysis of PHPT patients with (eGFR < 60 ml/min per 1.73 m(2)) and without chronic kidney disease (CKD) from our previously described PHPT cohort recruited from 1984 to 1991. SETTING: The study was conducted in a university hospital metabolic bone unit. PARTICIPANTS: One hundred thirty-eight women and men with PHPT were studied. OUTCOME MEASURES: We assessed bone mineral density (BMD) by dual-energy x-ray absorptiometry; quantitative histomorphometric indices from transiliac bone biopsies; and biochemical markers of mineral metabolism. RESULTS: Although there was no difference in serum or urinary calcium or PTH level, calcitriol levels were lower and phosphate levels higher in patients with CKD. BMD adjusted for weight did not differ at any site between groups. Histomorphometric analysis (n = 30 of 138) revealed a 45% greater eroded surface in those with CKD (P = 0.02). Eroded surface negatively correlated with eGFR (r = -0.46, P = 0.02) and phosphate (r = -0.48, P = 0.02) and positively correlated with serum calcium level (r = 0.51, P = 0.009) but not with PTH, alkaline phosphatase, vitamin D metabolites, or urinary calcium excretion. CONCLUSION: Although cardinal biochemical indices (such as calcium and PTH) and BMD do not differ in PHPT patients with an eGFR below 60 ml/min per 1.73 m(2), these patients have higher phosphate and histomorphometric evidence of altered bone remodeling compared with those without CKD.
PubMed-ID: 22399521
http://dx.doi.org/10.1210/jc.2011-3072
Anemia and Thrombocytopenia Improves After Curative Parathyroidectomy in a Patient of Primary Hyperparathyroidism (PHPT).
J Clin Endocrinol Metab, 97(5):1420-2.
Bhadada SK, Sridhar S, Ahluwalia J, Bhansali A, Malhotra P, Behera A, Mittal BR. 2012.
CONTEXT: Hematological manifestations are less known in primary hyperparathyroidism (PHPT). Anemia has been recognized as a complication of PHPT in 5-30% of the individuals in various series. OBJECTIVE: Our objective was to identify hematological improvement after the curative parathyroidectomy in a PHPT patient with anemia and thrombocytopenia. PATIENT AND METHODS: A 30-yr-old female presented with recurrent renal stone disease, anemia, and thrombocytopenia diagnosed as PHPT. Bone marrow examination revealed megakaryocytic thrombocytopenia. Two months after the curative parathyroidectomy, her symptoms and hematological parameters were improved. CONCLUSION: Our finding showed a causal association of both anemia and thrombocytopenia with marrow fibrosis in a symptomatic PHPT patient because both anemia and thrombocytopenia improved after the curative parathyroidectomy.
PubMed-ID: 22419706
http://dx.doi.org/10.1210/jc.2011-2845
Diagnosis and Management of Primary Hyperparathyroidism.
BMJ, 344:e1013.
Pallan S, Rahman MO, Khan AA. 2012.
PubMed-ID: 22431655
Classification of Parathyroid Cancer.
Ann Surg Oncol, 19(8):2620-8.
Schulte KM, Gill AJ, Barczynski M, Karakas E, Miyauchi A, Knoefel WT, Lombardi CP, Talat N, Diaz-Cano S, Grant CS. 2012.
PURPOSE: Parathyroid cancer is rare and often has a poor outcome. There is no classification system that permits prediction of outcome in patients with parathyroid cancer. This study was designed to validate two prognostic classification systems developed by Talat and Schulte in 2010 ("Clinical Presentation, Staging and Long-term Evolution of Parathyroid Cancer," Ann Surg Oncol 2010;17:2156-74) derived from a retrospective literature review of 330 patients. METHODS: This study contains 82 formerly unreported patients with parathyroid cancer. Death due to disease was the primary end point, and recurrence and disease-free survival were the secondary end points. Data acquisition used a questionnaire of predefined criteria. Low risk was defined by capsular and soft tissue invasion alone; high risk was defined by vascular or organ invasion, and/or lymph node or distant metastasis. A differentiated classification system further classified high-risk cancer into vascular invasion alone (class II), lymph node metastasis or organ invasion (class III), and distant metastasis (class IV). Statistical analyses included risk analysis, Kaplan-Meier analysis, and receiver-operating characteristic (ROC) analysis. RESULTS: Follow-up ranged 2-347 months (mean 76 months). Mortality was exclusive to the high- risk group, which also predicted a significant risk of recurrence (risk ratio 9.6; 95% confidence interval 2.4-38.4; P < 0.0001), with significantly lower 5-year disease-free survival (chi(2) = 8.7; P < 0.005 for n = 45). The differentiated classification also provided a good prognostic model with an area under the ROC curve of 0.83 in ROC analysis, with significant impairment of survival between classes (98.6%, 79.2%, 71.4%, 40.0%, P < 0.05 between each class). CONCLUSIONS: This study confirms the validity of both classification systems for disease outcome in patients with parathyroid cancer.
PubMed-ID: 22434247
http://dx.doi.org/10.1245/s10434-012-2306-6
Primary Hyperparathyroidism and Negative Tc99 Sestamibi Imaging: to Operate or Not?
Ann Surg Oncol, 19(7):2272-8.
Dy BM, Richards ML, Vazquez BJ, Thompson GB, Farley DR, Grant CS. 2012.
BACKGROUND: The indications for surgery in primary hyperparathyroidism (1HPT) are the same for patients with and without localization on imaging. However, patients with negative imaging may not be referred for surgery or the surgeon may be reluctant to operate. We compare outcomes in patients with negative imaging to those with localization. METHODS: A review of patients who underwent primary operation for 1HPT with a preoperative Tc99 sestamibi I-123 (MIBI) scan was conducted. Imaging, laboratory, operative findings, pathologic findings, and outcomes were used to compare patients with negative scans to those with localization. RESULTS: A total of 2,681 patients had an operation for 1HPT with preoperative MIBI. MIBI imaging was negative in 136 (5.7 %). The negative MIBI group had a lower calcium (10.9 vs. 11.0 mg/ml, P=0.02), phosphorus (2.9 vs. 3.1 mg/dl, P<0.001), and urinary calcium (251 vs. 287 mg/ml, P=0.02) and no difference in parathyroid hormone, 25-OH vitamin D, or bone loss. Multigland resection was higher with a negative scan (32 vs. 13 %, P<0.001). A curative operation was performed in 90.4 % with a negative MIBI compared to 97.5 % with localization (P<0.001). Patients who underwent successful surgery despite a negative MIBI scan had lower calcium (10.8 vs. 11.1 mg/ml, P=0.04) and parathyroid hormone (98 vs. 196 pg/ml, P=0.03) than those not cured. Patients with both a negative ultrasound result and negative MIBI had a cure rate of 89 %. CONCLUSIONS: A curative operation is performed at an acceptably lower rate with negative MIBI imaging. A decision for surgery with a negative MIBI finding should consider lower cure rates and symptom severity.
PubMed-ID: 22437201
http://dx.doi.org/10.1245/s10434-012-2325-3
An Unusual Ectopic Location of a Parathyroid Carcinoma Arising Within the Thyroid Gland.
J Clin Endocrinol Metab, 97(6):1829-33.
Cook MI, Qureshi YA, Todd CE, Cummins RS. 2012.
INTRODUCTION: Parathyroid carcinomas are very rare tumors and may arise in the normally located or ectopic gland. The latter present certain diagnostic difficulties, and there are no specific guidelines on their management. We present a case of parathyroid carcinoma arising within an ectopically located intrathyroid gland and discuss the diagnosis, management, and difficulties encountered. Furthermore, we review all six previously reported cases of this rare event and demonstrate the patterns in presentation, as well as the differences in management. CASE PRESENTATION: A 39-yr-old male presented with a right neck mass with biochemical derangement suggestive of a parathyroid lesion. However, radiological investigations were inconclusive as to the true nature of this lesion because they demonstrated a mass within the right thyroid lobe. A sestamibi (99m)technetium subtraction study was performed, which suggested an intrathyroid parathyroid carcinoma. The patient underwent successful surgical intervention. CONCLUSION: Although rare, ectopically located parathyroid glands can harbor malignant disease. Those located within the thyroid gland can be difficult to diagnose, and thus a combination of radiological modalities, including sestamibi (99m)technetium studies, need to be utilized. Although surgical resection is the most effective treatment, there are no specific guidelines as to the radicality of such treatment.
PubMed-ID: 22466351
http://dx.doi.org/10.1210/jc.2011-3115
Primary Hyperparathyroidism in MEN1 Patients: a Cohort Study With Longterm Follow-Up on Preferred Surgical Procedure and the Relation With Genotype.
Ann Surg, 255(6):1171-8.
Pieterman CR, van Hulsteijn LT, den HM, van der Luijt RB, Bonenkamp JJ, Hermus AR, Borel Rinkes IH, Vriens MR, Valk GD. 2012.
OBJECTIVE: To identify the optimal surgical strategy for multiple endocrine neoplasia type 1 (MEN1)-related primary hyperparathyroidism (pHPT). To describe the course of postoperative hypoparathyroidism and to assess whether genotype is associated with persistent/recurrent pHPT. BACKGROUND: Surgery is the preferred treatment in MEN1-related pHPT, but the surgical procedure of choice is still uncertain. METHODS: This retrospective cohort study was performed at the Departments of Endocrinology of the University Medical Centers of Utrecht and Nijmegen, the Netherlands. Patients were selected from the Dutch MEN1 database, including all patients 16 years or older treated for MEN1 from 1990 to 2009. Data were collected by medical record review. RESULTS: Seventy-three patients underwent parathyroid surgery. Persistent/recurrent pHPT occurred in 53% after less than 3 parathyroids resected (<SPTX), 17% after subtotal resection (SPTX), and 19% after total resection with autotransplantation (TPTX). Persistent (>/=6 months) postoperative hypoparathyroidism occurred in 24% after <SPTX, 39% after SPTX, and 66% after TPTX. Median duration of hypoparathyroidism was 1.5 years, in 65% successful cessation of vitamin D/calcium was possible, even after more than 10 years. After <SPTX, patients with nonsense or frameshift mutations in exons 2, 9, and 10 had a significantly lower risk of persistent/recurrent pHPT than patients with other mutations. After SPTX/TPTX persistence/recurrence did not differ with genotype. After SPTX/TPTX persistence/recurrence was more frequent (P = 0.07) in patients without bilateral transcervical thymectomy (TCT). CONCLUSIONS: SPTX with bilateral TCT is the procedure of choice for MEN1-related pHPT. Genotype seems to affect the chance of recurrence. Postoperative hypoparathyroidism lasting 6 months or more should not be considered permanent in MEN1.
PubMed-ID: 22470073
http://dx.doi.org/10.1097/SLA.0b013e31824c5145
Calcimimetics Versus Parathyroidectomy for Treatment of Primary Hyperparathyroidism: Retrospective Chart Analysis of a Prospective Database.
Ann Surg, 255(5):981-5.
Keutgen XM, Buitrago D, Filicori F, Kundel A, Elemento O, Fahey TJ, III, Zarnegar R. 2012.
OBJECTIVE: This study aims to determine the efficacy of calcimimetics in improving bone mineral density (BMD) in patients with primary hyperparathyroidism (pHPT) and compare those results to patients undergoing parathyroidectomy. BACKGROUND: Parathyroidectomy has been shown to improve BMD in pHPT, but calcimimetics have recently been advocated as a medical alternative to parathyroidectomy for pHPT. MATERIALS AND METHODS: We identified 17 patients that were treated with calcimimetics for pHPT. Seventeen patients with pHPT who underwent parathyroidectomy served as surgical controls. Serum calcium level, parathyroid hormone (PTH) level, and femur and spine BMD T scores were compared before and 1 year after therapy. RESULTS: Both groups were demographically matched. Calcium levels normalized in 70.6% of medically versus 100% of surgically treated patients (P = 0.026). PTH levels normalized in 35% of patients treated with calcimimetics versus 76% of surgical patients (P = 0.036). Femur BMD improved in 18.8% of medically treated patients versus 58.8% of surgical patients (P = 0.032). Spine BMD improved in 70.6% of medically treated patients versus 82.4% of surgical patients (P = 0.69). Further analysis demonstrated that regardless of treatment, normalization of PTH was associated with significant improvement in femur (P = 0.03) and spine BMD (P < 0.001). Normalization of calcium without normalization of PTH did not impact BMD. CONCLUSIONS: Parathyroidectomy results in greater normalization of serum calcium and PTH levels and significantly improves cortical BMD compared to calcimimetics. Regardless of treatment, normalization of PTH is associated with significant improvement in spine and femur BMD, suggesting that the superior effects of surgery may be mediated by better control of PTH.
PubMed-ID: 22470074
http://dx.doi.org/10.1097/SLA.0b013e31824c5252
Incidence of Concomitant Hyperparathyroidism in Patients With Thyroid Disease Requiring Surgery.
J Surg Res, 178(1):264-7.
Murray SE, Sippel RS, Chen H. 2012.
BACKGROUND: Thyroid disease and hyperparathyroidism (HPT) are among the most common endocrine disorders, however, their association has not been well established. The aim of the present study was to determine the incidence of concomitant HPT in patients with thyroid disease requiring surgery, because a single definitive surgery should ideally be performed. METHODS: We retrospectively reviewed a prospectively maintained database of patients who underwent thyroidectomy at a single institution. Data collected included the patients' initial indication for surgery, preoperative workup, and operative findings. RESULTS: Of the 1,049 patients who underwent thyroidectomy, 56 (5%) had concomitant HPT and underwent simultaneous parathyroidectomy. Of these 56 patients, 36 initially presented with thyroid disease and 20 with HPT. The mean age was 59 +/- 2 years, and 79% were women. The mean preoperative calcium and parathyroid hormone levels were elevated at 10.4 +/- 0.1 mg/dL and 87 +/- 7 pg/mL, respectively. Most of these patients had primary HPT (n = 54, 96%). Of the 36 patients presenting initially with thyroid disease, 26 had an elevated calcium or parathyroid hormone value and were preoperatively diagnosed with HPT. The remaining 10 patients had normal laboratory findings; however, a pathologically enlarged parathyroid gland was found at thyroidectomy. The overall cure rate for HPT within our series was 96%. CONCLUSION: The incidence of concomitant HPT in patients with thyroid disease requiring surgery is significant at 5%. Recognition of concurrent disease is important, because it allows for a single definitive surgery to treat both pathologies.
PubMed-ID: 22482770
http://dx.doi.org/10.1016/j.jss.2012.03.008
Sleeping Parathyroid Tumor: Rapid Hyperfunction After Removal of the Dominant Tumor.
J Clin Endocrinol Metab, 97(6):1834-41.
Yavuz S, Simonds WF, Weinstein LS, Collins MT, Kebebew E, Nilubol N, Phan GQ, Libutti SK, Remaley AT, Van DM, Marx SJ. 2012.
CONTEXT: Due to frequent multiplicity of tumors in multiple endocrine neoplasia type 1, it may be difficult to decide when to stop a parathyroid exploration. A fall of intraoperative serum PTH by a certain percentage during parathyroid surgery is often used as one criterion for ending the operation. RESULTS: We report two patients with primary hyperparathyroidism due to multiple endocrine neoplasia type 1 who had their first parathyroidectomy at the National Institutes of Health. In both cases, two and a half glands were removed, an extensive search was done for an occult parathyroid tumor, and intraoperative PTH decreased markedly to the lower limits of normal, suggesting a successful operation. Despite this, both patients became hypercalcemic within 3 d after the operation and showed persistent primary hyperparathyroidism. Detailed findings suggest the following course: chronic hypercalcemia had caused near total suppression of PTH secretion by an undiscovered parathyroid tumor (sleeping parathyroid tumor). When the hypercalcemia decreased after surgery due to the removal of the dominant parathyroid tumor(s), the abnormal yet previously suppressed tumor rapidly began to oversecrete PTH and thus caused postoperative hypercalcemia. CONCLUSIONS: Even a fall of the intraoperative PTH to the lower limits of the normal range cannot guarantee that removal of all parathyroid tumors has been complete in cases with multiple tumors. These findings likely reflect strikingly differing PTH secretory functions among distinct tumors in the same patient, with hypercalcemia at least from a dominant tumor suppressing PTH secretion by one or more other parathyroid tumors.
PubMed-ID: 22508712
http://dx.doi.org/10.1210/jc.2011-3030
Sestamibi-Negative Patients: to Operate or Image?
Ann Surg Oncol, 19(7):2086-7.
Lubitz CC, Chen H. 2012.
PubMed-ID: 22526912
http://dx.doi.org/10.1245/s10434-012-2369-4
Total Parathyroidectomy Versus Subtotal Parathyroidectomy in the Treatment of Tertiary Hyperparathyroidism.
Am Surg, 78(5):600-6.
Hsieh TM, Sun CK, Chen YT, Chou FF. 2012.
The purposes of this study are to evaluate the merits of surgical treatment, including subtotal parathyroidectomy (SP) and total parathyroidectomy (TP), in patients with tertiary hyperparathyroidism (THPT) and compare the outcome of the two surgical options. Medical records of patients undergoing parathyroidectomy for THPT were retrospectively reviewed and long-term outcomes between the two groups were compared. Fourteen out of 488 renal transplantation recipients required parathyroidectomy for THPT during a 24-year follow-up period with a median follow-up of 35.5 [interquartile range (IQR), 19.3-133.3] months. All patients had hypercalcemia, whereas 13 had varying symptoms and one was asymptomatic. Median serum calcium level decreased from 12.4 (IQR, 11.9-12.6) mg/dL preoperatively to 8.9 (IQR, 8.1-9.4) mg/dL postoperatively (P = 0.001), whereas median intact parathyroid hormone (iPTH) dropped from a preoperative level of 340.5 (IQR, 247-540) pg/mL to 55.1 (IQR, 24.4-66.4) pg/mL after surgery (P = 0.018). Comparison between patients receiving TP and SP revealed no difference in incidence of recurrence or permanent complications, whereas the former had significantly lower calcium levels (P = 0.048) and higher phosphorus levels (P = 0.017) compared with the latter. Moreover, a significant reduction in calcium level was noted in TP group on long-term follow-up compared with their immediately postoperative level (8.1 vs 9.0 mg/dL, respectively, P < 0.05), whereas there was no significant decrease in SP group. We concluded that parathyroidectomy is efficient and safe in treating THPT. Because TP would increase the risk of hypocalcemia, a less radical procedure (SP) is preferred.
PubMed-ID: 22546135
Surgery for Primary Hyperparathyroidism: Are the Consensus Guidelines Being Followed?
Ann Surg, 255(6):1179-83.
Yeh MW, Wiseman JE, Ituarte PH, Pasternak JD, Hwang RS, Wu B, Liu IL, Haigh PI. 2012.
OBJECTIVE: To determine parathyroidectomy (PTx) rates in patients who satisfy the consensus guidelines for surgical treatment of primary hyperparathyroidism (PHPT). BACKGROUND: Surgery for PHPT is recommended for all symptomatic patients and select asymptomatic patients meeting established consensus criteria. Adherence to the consensus guidelines has not been examined systematically, because of inadequate information regarding patients managed nonoperatively. METHODS: All nonuremic patients with PHPT during the period 1995-2008 were identified using the Kaiser Permanente-Southern California laboratory database, encompassing 3.5 million individuals annually. Multivariate logistic regression was used to examine predictors of PTx. RESULTS: We found 3388 patients with PHPT, of whom 265 (8%) were symptomatic (nephrolithiasis). Nephrolithiasis was predictive of PTx (OR 2.94 vs asymptomatic), with 51% of symptomatic patients undergoing surgery. Among asymptomatic patients, the proportion meeting consensus criteria was 39% during the early period (1995-2002) and 51% during the late period (2003-2008). The PTx rate for these patients exceeded that for asymptomatic patients not meeting consensus criteria but remained low (early 44% vs 19%, P < 0.0001; late 39% vs 16%, P < 0.0001). The following individual criteria were predictive of PTx: calcium >11.5 mg/dL (OR 2.27), hypercalciuria (OR 3.28, P < 0.0001), and age < 50 years (OR 1.54, P < 0.0001). However, the absolute PTx rates associated with satisfaction of these criteria were in the 50% range. Bone density scores did not influence likelihood of PTx and renal impairment predicted against PTx (OR 0.35, P < 0.0001). CONCLUSIONS: The consensus guidelines regarding PHPT have not been followed in our study population. PTx appears to be underutilized in both asymptomatic and symptomatic patients.
PubMed-ID: 22584631
http://dx.doi.org/10.1097/SLA.0b013e31824dad7d
Effect of Parathyroidectomy on Subclinical Cardiovascular Disease in Mild Primary Hyperparathyroidism.
Eur J Endocrinol, 167(2):277-85.
Walker MD, Rundek T, Homma S, DiTullio M, Iwata S, Lee JA, Choi J, Liu R, Zhang C, McMahon DJ, Sacco RL, Silverberg SJ. 2012.
OBJECTIVE: We recently demonstrated that mild primary hyperparathyroidism (PHPT) is associated with increased carotid intima-media thickness (IMT) and stiffness, and increased aortic valve calcification. It is unclear whether parathyroidectomy (PTX) improves these abnormalities. The purpose of this study was to determine whether cardiovascular abnormalities in PHPT improve with PTX. DESIGN: Forty-four patients with PHPT were studied using carotid ultrasound and transthoracic echocardiography before and after PTX. Carotid IMT, carotid plaque and stiffness, left ventricular mass index (LVMI), myocardial and valvular calcification, and diastolic function were measured before, 1- and 2-year post-PTX. RESULTS: Two years after PTX, increased carotid stiffness tended to decline to the normal range (17%, P=0.056) while elevated carotid IMT did not improve. Carotid plaque number and thickness, LVMI and cardiac calcifications did not change after PTX, while some measures of diastolic function (isovolumic relaxation time (IVRT) and tissue Doppler peak early diastolic velocity) worsened within the normal range. Indices did improve in patients with cardiovascular abnormalities at baseline. Increased carotid stiffness improved by 28% (P=0.004), a decline likely to be of clinical significance. More limited improvements also occurred in elevated IMT (3%, P=0.017) and abnormal IVRT (13%, P<0.05), a measure of diastolic dysfunction. CONCLUSIONS: In mild PHPT, PTX led to modest changes in some cardiovascular indices. Improvements were mainly evident in those with preexisting cardiovascular abnormalities, particularly elevated carotid stiffness. These findings are reassuring with regard to current international guidelines that do not include cardiovascular disease as a criterion for PTX.
PubMed-ID: 22660025
http://dx.doi.org/10.1530/EJE-12-0124
Surgical Approach and Outcomes in Patients With Lithium-Associated Hyperparathyroidism.
Ann Surg Oncol, 19(11):3465-71.
Marti JL, Yang CS, Carling T, Roman SA, Sosa JA, Donovan P, Guoth MS, Heller KS, Udelsman R. 2012.
BACKGROUND: Patients receiving lithium therapy are at elevated risk of developing hyperparathyroidism. In lithium-associated hyperparathyroidism (LAH), the incidence of multiglandular disease (MGD) is unclear, and the need for routine bilateral cervical exploration remains controversial. Therefore, in LAH patients, surgical approaches, pathologic findings, cure rates, and factors associated with persistent or recurrent disease were investigated. METHODS: Retrospective analysis of 27 patients with LAH undergoing parathyroidectomy with the intraoperative parathyroid hormone (PTH) assay. RESULTS: The median postoperative follow-up was 7 months; 17 patients had >6 months follow-up. Cervical exploration was unilateral in 9, bilateral in 18 (3 were converted from unilateral). Sixteen patients (62%) had MGD, 12 with four-gland hyperplasia and 4 with double adenomas. Ten patients (38%) had a single adenoma. Twenty-five (93%) of 27 patients had initially successful surgery. Of the 17 patients with >6 months follow-up, two had persistent disease and two experienced recurrent disease. All patients with a single adenoma remain free of disease. Three (75%) of four patients with persistent/recurrent disease had MGD and were receiving lithium at the time of surgery. Patients with persistent/recurrent disease were older (p = 0.01) and had experienced a longer duration of hypercalcemia (p = 0.04). CONCLUSIONS: LAH patients have a high incidence of MGD, and bilateral exploration is frequently necessary. With access to the intraoperative PTH assay, it is reasonable to initiate a unilateral approach because many patients will harbor single adenomas and can be reliably rendered normocalcemic. Patients with MGD remain at higher risk of persistent/recurrent disease.
PubMed-ID: 22669448
http://dx.doi.org/10.1245/s10434-012-2367-6
Tertiary Hyperparathyroidism in Kidney Transplant Recipients: Characteristics of Patients Selected for Different Treatment Strategies.
Transplantation, 94(1):70-6.
Yang RL, Freeman K, Reinke CE, Fraker DL, Karakousis GC, Kelz RR, Doyle AM. 2012.
BACKGROUND: Several treatment options exist for kidney transplant patients with tertiary hyperparathyroidism. However, the decision to endorse observation (OBS), medical therapy, or parathyroidectomy (PTX) remains controversial. METHODS: We performed a retrospective cohort study of kidney transplant patients with tertiary hyperparathyroidism at a single institution over a 7-year period. Patients were classified by treatment mode: OBS, medical therapy with cinacalcet (CIN), or PTX. Descriptive statistics were performed. Serum calcium levels and change in serum creatinine level were compared using analysis of variance with comparisons between individual groups using the Student's t test with a Bonferroni correction. Time to treatment was compared between CIN and PTX groups using the Student's t test. Complication rates were compared using the Fisher exact test. RESULTS: We identified 83 patients: 52 were treated by OBS; 13 were treated with CIN, and 18 underwent PTX. Six weeks after treatment, PTX resulted in lower serum calcium level (9.28 mg/dL) compared with CIN (10.20 mg/dL) (P<0.01). There was no difference in the change in serum creatinine level 1 year after treatment initiation (P=0.98). Time to treatment was shorter (1.7 vs. 3.3 years, P<0.01), and the highest pretreatment calcium level was higher (12.2 vs. 11.7 mg/dL, P<0.01) in patients treated with PTX compared with CIN. Complication rates differed by treatment group (P<0.01). A quarter of OBS patients showed persistent hypercalcemic symptoms, compared with only 7.7% in the CIN group and 0% in the PTX group (P<0.01). CONCLUSIONS: PTX led to a greater reduction in serum calcium level and lower chance of persistent hypercalcemic symptoms, without any appreciable harm to the kidney allograft.
PubMed-ID: 22706321
http://dx.doi.org/10.1097/TP.0b013e3182530699
Arterial Hypertension, Metabolic Syndrome and Subclinical Cardiovascular Organ Damage in Patients With Asymptomatic Primary Hyperparathyroidism Before and After Parathyroidectomy: Preliminary Results.
Int J Endocrinol, 2012:408295.
Luigi P, Chiara FM, Laura Z, Cristiano M, Giuseppina C, Luciano C, Giuseppe P, Sabrina C, Susanna S, Antonio C, Giuseppe C, Giorgio dT, Claudio L. 2012.
Background. Primary hyperparathyroidism (PHPT) is associated with high cardiovascular morbidity, and the role of calcium and parathyroid hormone is still controversial. Objective. To evaluate the prevalence and outcomes of metabolic syndrome, hypertension, and some cardiovascular alterations in asymptomatic PHPT, and specific changes after successful parathyroidectomy. Material and Methods. We examined 30 newly diagnosed PHPT patients (8 males, 22 females; mean age 56 +/- 6 yrs), 30 patients with essential hypertension (EH) (9 males, 21 females; mean age 55 +/- 4), and 30 normal subjects (NS) (9 males, 21 females: mean age 55 +/- 6). All groups underwent evaluation with ambulatory monitoring blood pressure, echocardiography, and color-Doppler artery ultrasonography and were successively revaluated after one year from parathyroidectomy. Results. PHPT patients presented a higher prevalence of metabolic syndrome (38%) with respect to EH (28%). Prevalence of hypertension in PHPT was 81%, and 57% presented altered circadian rhythm of blood pressure, with respect to EH (35%) and NS (15%). PHPT showed an important myocardial and vascular remodelling. During follow-up in PHPT patients, we found significant reduction of prevalence of metabolic syndrome, blood pressure, and "non-dipping phenomenon." Conclusions. Cardiovascular and metabolic alterations should be considered as added parameters in evaluation of patients with asymptomatic PHPT.
PubMed-ID: 22719761
http://dx.doi.org/10.1155/2012/408295
An Intrathyroidal Parathyroid: Thyroid Vein Sampling Prior to Lobectomy.
Am Surg, 78(7):818-9.
Abdo A, Kowdley GC. 2012.
PubMed-ID: 22748545
Creation of a "Wisconsin Index" Nomogram to Predict the Likelihood of Additional Hyperfunctioning Parathyroid Glands During Parathyroidectomy.
Ann Surg, 
Mazeh H, Chen H, Leverson G, Sippel RS. 2012.
OBJECTIVE:: The aim of our study was to create a preoperative "index" that could predict the likelihood of additional hyperfunctioning parathyroid glands and let the surgeon determine whether to wait for the intraoperative parathyroid hormone (ioPTH) or to explore further. BACKGROUND:: During parathyroidectomy for primary hyperparathyroidism (PHPT), discovering a minimally "enlarged" parathyroid gland creates a dilemma for the surgeon regarding the need for further exploration. Although ioPTH testing can potentially solve this problem after a 20- to 30-minute period, several surgeons recognize that further operative exploration may be more effective. METHODS:: We analyzed a prospective database of 1235 consecutive patients who underwent parathyroidectomy for PHPT at our institution between March 2001 and August 2010. The Wisconsin Index (WIN) was defined as the multiplication of preoperative serum calcium by preoperative parathyroid hormone (PTH). Patients were divided into 3 WIN categories: low (<800), medium (801-1600), and high (>1600). The utility of the WIN was then validated on a subsequent cohort of 216 patients. RESULTS:: The median age of the patients was 61 years (range, 10-91), and 77% of the patients were female. The mean preoperative calcium and PTH levels were 11.0 +/- 0 mg/dL and 127 +/- 3 pg/mL, respectively. The mean WIN for the entire cohort was 1461 +/- 38 and highly correlated with gland weight (P < 0.000001). A single adenoma was identified in 1000 patients (81%), double adenoma in 100 patients (8%), and hyperplasia in 135 patients (11%). The mean gland weights for the 3 WIN catagories were low = 370 +/- 33 mg, medium = 532 +/- 39 mg, and high = 985 +/- 28 mg, respectively (P < 0.000001). A WIN nomogram, consisting of the combination of WIN and parathyroid gland weight, accurately predicted the likelihood of additional hyperfunctioning parathyroid glands. For example, for a WIN of less than 800 and a gland weight of 500 mg, there is a 9% chance for additional hyperfunctioning parathyroid glands based on the WIN nomogram. In contrast, for the same gland weight, if the WIN is 801 to 1600, these chances increase to 28%, and if the WIN is more than 1600, the chance of multigland disease is 61%. Comparison between the predicted chances for another gland with the actual chance in the validation cohort identified an R value of 0.96. CONCLUSIONS:: The WIN nomogram predicts the likelihood of additional hyperfunctioning parathyroid glands during parathyroidectomy. This simple intraoperative tool may be used to guide the decision of whether to wait for ioPTH results or to proceed with further neck exploration.
PubMed-ID: 22801087
http://dx.doi.org/10.1097/SLA.0b013e31825ffbe1
Treatment of Secondary Hyperparathyroidism With Parathyroidectomy Instead of Cinacalcet: Time to Pick the Low-Hanging Fruit?
Am J Kidney Dis, 60(2):179-81.
Yuan CM, Nee R, Narayan R, Abbott KC. 2012.
PubMed-ID: 22805518
http://dx.doi.org/10.1053/j.ajkd.2012.05.004
An Unusual Association of Cerebral Schwannoma, Parathyroid Adenoma, and Papillary Thyroid Carcinoma.
Am Surg, 78(8):E375-E376.
Manchanda C, Nagpal K, Cosgrove JM, Saraiya R. 2012.
PubMed-ID: 22856482
Parathyroidectomies Using Intraoperative Parathormone Monitoring: When Should We Stop Measuring Intraoperative Parathormone Levels?
Am Surg, 78(8):844-50.
Gupta A, Unawane A, Subhas G, Herschman BR, Silapaswan S, Kolachalam R, Kestenberg W, Ferguson L, Jacobs MJ, Mittal VK. 2012.
Intraoperative parathyroid hormone monitoring (IOPM), in use for the last 15 years, has facilitated focused parathyroidectomy. We undertook this study to determine if a drop in IOPT hormone levels below 50 per cent of baseline were sufficient to terminate the procedure. We conducted a retrospective chart review (January 2007 to September 2010) of 104 patients who underwent initial parathyroidectomies with IOPM by general surgeons for primary hyperparathyroidism. Patients were followed up for serum calcium levels (range, 6 to 48 months). The number of specimens excised was significantly decreased when IOPT hormone levels dropped to greater than 50 per cent and came within the normal range earlier. Moreover, for single-gland parathyroid adenomas, once the parathyroid hormone values dropped to less than 50 per cent in the 5-minute sample, they continued to decrease in the subsequent samples. In 23 cases requiring further exploration, the parathyroid hormone values had already decreased to greater than 50 per cent in 14 cases but had not normalized (reference range, 8 to 74), leading to additional exploration. However, subsequent pathologic analysis showed that the initial gland removed was the adenoma in all these cases. A drop in the initial 5-minute parathyroid hormone value to less than 50 per cent of the baseline should serve as sufficient evidence to terminate the procedure. This would translate into significant laboratory and personnel cost savings over time. However, this should be carefully correlated with preoperative ultrasound/sestamibi findings.
PubMed-ID: 22856490

Adrenals
Meta-Analyses
- None -
Randomized controlled trials
Single-Incision Transperitoneal Laparoscopic Left Adrenalectomy.
World J Surg, 36(6):1395-9.
Vidal O, Astudillo E, Valentini M, Ginesta C, Garcia-Valdecasas JC, Fernandez-Cruz L. 2012.
BACKGROUND: Laparoscopic adrenalectomy via three or four trocars is a well-established procedure. This report describes the initial experience with single-incision laparoscopic surgery (SILS) using the transperitoneal approach for left adrenalectomy. METHODS: Between April 2010 and August 2011, all consecutive patients with adrenal masses, including Conn's syndrome, Cushing's adenoma, and nonfunctional adrenal tumors, who agreed to undergo SILS adrenalectomy were included in a prospective study. The left 2.5-cm subcostal incision was the sole point of entry. Data of patients who underwent SILS adrenalectomy were compared with those from an uncontrolled group of patients who underwent conventional laparoscopic adrenalectomy during the same study period. RESULTS: There were 20 patients in each study group (20 men, 20 women; mean age [SD] = 50 [6.5] years). SILS was successfully performed and none of the patients required conversion to an open procedure. In one case of SILS procedure, an additional lateral 5-mm port was needed for retraction of the kidney. The mean (SD) duration of the operation was 95 (20) min in the SILS group and 80 (8) min in the conventional laparoscopic adrenalectomy group (p = 0.052). There were no intraoperative or postoperative complications. There were no differences between the two study groups with respect to postoperative pain, number of patients who resumed oral intake within the first 24 h, final pathologic diagnosis, and length of hospital stay. CONCLUSION: SILS left adrenalectomy is a technically feasible and safe procedure in carefully selected patients. The definitive clinical, aesthetic and functional advantages of this technique require further analysis.
PubMed-ID: 22392358
http://dx.doi.org/10.1007/s00268-012-1555-7
Combination Chemotherapy in Advanced Adrenocortical Carcinoma.
N Engl J Med, 366(23):2189-97.
Fassnacht M, Terzolo M, Allolio B, Baudin E, Haak H, Berruti A, Welin S, Schade-Brittinger C, Lacroix A, Jarzab B, Sorbye H, Torpy DJ, Stepan V, Schteingart DE, Arlt W, Kroiss M, Leboulleux S, Sperone P, Sundin A, Hermsen I, Hahner S, Willenberg HS, Tabarin A, Quinkler M, de la Fouchardiere C, Schlumberger M, Mantero F, Weismann D, Beuschlein F, Gelderblom H, Wilmink H, Sender M, Edgerly M, Kenn W, Fojo T, Muller HH, Skogseid B. 2012.
BACKGROUND: Adrenocortical carcinoma is a rare cancer that has a poor response to cytotoxic treatment. METHODS: We randomly assigned 304 patients with advanced adrenocortical carcinoma to receive mitotane plus either a combination of etoposide (100 mg per square meter of body-surface area on days 2 to 4), doxorubicin (40 mg per square meter on day 1), and cisplatin (40 mg per square meter on days 3 and 4) (EDP) every 4 weeks or streptozocin (streptozotocin) (1 g on days 1 to 5 in cycle 1; 2 g on day 1 in subsequent cycles) every 3 weeks. Patients with disease progression received the alternative regimen as second-line therapy. The primary end point was overall survival. RESULTS: For first-line therapy, patients in the EDP-mitotane group had a significantly higher response rate than those in the streptozocin-mitotane group (23.2% vs. 9.2%, P<0.001) and longer median progression-free survival (5.0 months vs. 2.1 months; hazard ratio, 0.55; 95% confidence interval [CI], 0.43 to 0.69; P<0.001); there was no significant between-group difference in overall survival (14.8 months and 12.0 months, respectively; hazard ratio, 0.79; 95% CI, 0.61 to 1.02; P=0.07). Among the 185 patients who received the alternative regimen as second-line therapy, the median duration of progression-free survival was 5.6 months in the EDP-mitotane group and 2.2 months in the streptozocin-mitotane group. Patients who did not receive the alternative second-line therapy had better overall survival with first-line EDP plus mitotane (17.1 month) than with streptozocin plus mitotane (4.7 months). Rates of serious adverse events did not differ significantly between treatments. CONCLUSIONS: Rates of response and progression-free survival were significantly better with EDP plus mitotane than with streptozocin plus mitotane as first-line therapy, with similar rates of toxic events, although there was no significant difference in overall survival. (Funded by the Swedish Research Council and others; FIRM-ACT ClinicalTrials.gov number, NCT00094497.).
PubMed-ID: 22551107
http://dx.doi.org/10.1056/NEJMoa1200966
Other Articles
What Is the Best Criterion for the Interpretation of Adrenal Vein Sample Results in Patients With Primary Hyperaldosteronism?
Ann Surg Oncol, 19(6):1881-6.
Webb R, Mathur A, Chang R, Baid S, Nilubol N, Libutti SK, Stratakis CA, Kebebew E. 2012.
BACKGROUND: In patients with primary hyperaldosteronism, adrenal vein sampling (AVS) has emerged as a gold standard for distinguishing between unilateral and bilateral disease, but multiple criteria have been used and no consensus exists as to the most accurate criterion. The objective of this study was to determine which AVS criteria most accurately identify patients with unilateral surgical disease and are associated with significant clinical improvement after adrenalectomy. METHODS: This is a retrospective analysis of AVS results in 108 patients with primary hyperaldosteronism treated at a single institution. Literature review of AVS criteria was used to distinguish between unilateral and bilateral disease. RESULTS: Of the 10 AVS criteria identified in the literature, one criterion (ACTH stimulation, positioning: cortisol [adrenal]/cortisol [periphery] [Ca/Cp] > 5.0 and lateralization: aldosterone/cortisol [A/C] [dominant {D}]: A/C [nondominant {ND}] > 4:1) was the most accurate in identifying and correctly predicting lateralization of disease (P value range: < 0.001-0.0369). For this criterion, the true positive rate was 88%. The second most accurate criterion was no ACTH stimulation, positioning Ca/Cp > 1.1 and lateralization: A/C (D): A/C (ND) > 2:1. For this criterion, the overall true positive was 85%. However, we found no significant difference in clinical outcome based on individual criteria fulfillment. CONCLUSIONS: Of the multiple criteria used for AVS evaluation, one criterion has the best accuracy. With the increasing use of AVS, there should be a consensus by which these results are evaluated and surgeons recommend adrenalectomy.
PubMed-ID: 22048631
http://dx.doi.org/10.1245/s10434-011-2121-5
Preoperative 18F-FDG Uptake Is Strongly Correlated With Malignancy, Weiss Score, and Molecular Markers of Aggressiveness in Adrenal Cortical Tumors.
World J Surg, 36(6):1406-10.
Gust L, Taieb D, Beliard A, Barlier A, Morange I, de MC, Henry JF, Sebag F. 2012.
BACKGROUND: Adrenal incidentaloma are frequent in the general population. It can be difficult to diagnose adrenocortical carcinomas among them, even with the progress of imaging techniques. We studied the results of PET-FDG in the diagnosis of such tumours. METHODS: We studied patients referred to the Department of Endocrine Surgery at La Timone Hospital, Marseilles, France, between June 2006 and October 2010 for adrenal tumours. All patients underwent a complete work-up (biological tests and imagery), completed with PET-FDG. We compared the results of PET-FDG and molecular analysis with Weiss score and clinical follow-up. We calculated correlations with the Pearson test. RESULTS: A total of 51 patients were studied. We found that PET-FDG had a sensitivity of 95% and specificity of 97% for the diagnosis of adrenocortical carcinoma. The correlation between PET-FDG and Weiss score was 77% (P </= 0.0001). Molecular analyses were correlated as well with Weiss score and malignancy (P < 0.05). CONCLUSIONS: The nature of atypical adrenal masses can be difficult to define during preoperative investigations. For undetermined tumours smaller than 6 cm, characterization with PET-FDG can be one more diagnostic argument pointing to malignancy. It could potentially change the therapeutic strategy and surgical management. In our experience, molecular analyses are available after surgery and have less impact on the therapeutic strategy than PET-FDG. Preoperative PET-FDG can be an asset in the management of adrenal incidentaloma and adrenocortical carcinoma.
PubMed-ID: 22131094
http://dx.doi.org/10.1007/s00268-011-1374-2
Operative Management for Recurrent and Metastatic Adrenocortical Carcinoma.
J Surg Oncol, 105(7):709-13.
Datrice NM, Langan RC, Ripley RT, Kemp CD, Steinberg SM, Wood BJ, Libutti SK, Fojo T, Schrump DS, Avital I. 2012.
OBJECTIVE: A review of all resections for recurrent or metastatic ACC was performed to identify patients who might benefit from a surgical approach, and to identify factors that might aid in prognosis among patients with metastatic disease. SUMMARY BACKGROUND DATA: Adrenocortical carcinoma (ACC) is a rare tumor, with frequent recurrences and metastases even after complete resection. Chemotherapy has limited efficacy, and surgical resection of metastatic ACC remains controversial. METHODS: A retrospective review was performed of all patients who underwent surgical intervention for metastatic ACC in a single tertiary center from 1977 to 2009. All available clinicopathologic data were analyzed to determine potential factors associated with response to treatment and survival. RESULTS: Fifty-seven patients underwent 116 procedures for recurrent or metastatic disease. Twenty-three resections were for liver metastases, 48 for pulmonary metastases, 22 for abdominal disease including local recurrences, and 13 were for metastases at other sites. Median and 5-year survivals from time of first metastasectomy were 2.5 years, and 41%, respectively. The median survival of patients with DFI <12 months was 1.7 years, compared to 6.6 years for patients with DFI >12 months (P = 0.015). Median survival for right versus left-sided primaries was 1.9 years versus 3.8 years (P = 0.03). Liver metastases were more common with right-sided primaries (67% vs. 41%, P = 0.05). Chemotherapy had no impact on survival. CONCLUSIONS: Resection of recurrent or metastatic ACC is safe, and may result in prolongation of survival in selected patients with DFI greater than 1 year.
PubMed-ID: 22189845
http://dx.doi.org/10.1002/jso.23015
Prevalence of Germline Mutations in Patients With Pheochromocytoma or Abdominal Paraganglioma and Sporadic Presentation: a Population-Based Study in Western Sweden.
World J Surg, 36(6):1389-94.
Muth A, Abel F, Jansson S, Nilsson O, Ahlman H, Wangberg B. 2012.
BACKGROUND: Germline mutations in the susceptibility genes RET, SDHB, SDHD, and VHL have been reported in 7.5-24% of patients with pheochromocytoma (Pheo) or paraganglioma (PGL) and sporadic presentation. The purpose of the present study was to establish population-based data on the frequency of germline mutations in patients with apparently sporadic Pheo or abdominal PGL in Western Sweden. METHODS: From the Swedish National Cancer Registry, all patients with Pheo or PGL in Western Sweden (population 1.72 million) registered between 1958 and 2009 were identified (n = 256). Patients were characterized using register data, hospital records, and clinical interviews. All living patients with Pheo or abdominal PGL and sporadic presentation (n = 81) were invited to genetic screening; 71 patients accepted. Germline mutations were investigated by using direct sequencing for point mutations in RET, SDHB, SDHD, and VHL, and multiplex ligation-dependent probe amplification for gross deletions in SDHB, SDHC, SDHD, and VHL. Plasma or urinary metanephrines and/or urinary catecholamines were used for biochemical follow-up. RESULTS: The prevalence of germline mutations was 5.6%. Mutations were only seen in RET (n = 1) and SDHB (n = 3). Notably, in the patients with SDHB mutations, no malignant phenotype was observed during a mean follow-up of 23.3 years. CONCLUSIONS: The frequency of germline mutations in patients with apparently sporadic Pheo and abdominal PGL in Western Sweden was lower than in previous studies. Variations in reported frequencies of germline mutations in patients with clinically sporadic Pheo/PGL may reflect geographical differences or patient selection.
PubMed-ID: 22270996
http://dx.doi.org/10.1007/s00268-012-1430-6
Ectopic Hormone-Secreting Pheochromocytoma: a Francophone Observational Study.
World J Surg, 36(6):1382-8.
Kirkby-Bott J, Brunaud L, Mathonet M, Hamoir E, Kraimps JL, Tresallet C, Amar L, Rault A, Henry JF, Carnaille B. 2012.
BACKGROUND: Ectopic hormone-secreting pheochromocytomas are rare; only case reports exist in the literature. This condition has been linked with increased malignancy, familial syndromes, and ACTH secretion. We wanted to test these hypotheses and shed light on the nature of ectopic hormone-secreting pheochromocytomas. METHODS: This is a multicenter (francophone) observational study. Inclusion was based upon abnormal preoperative hormone tests in patients with pheochromocytoma that normalized after removal of the tumor. Where possible, immunohistochemistry was performed to confirm that ectopic secretion came from the tumor. RESULTS: Sixteen cases were found: nine female and seven male patients. Median age was 50.5 (range 31-89) years. Most presented with hypertension, diabetes, or cushingoid features. Ten patients had specific symptoms from the ectopic hormone secretion. Two had a familial syndrome. Of eight patients with excess cortisol secretion, three died as a result of the tumor resection: two had pheochromocytomas >15 cm and their associated cortisol hypersecretion complicated their postoperative course. The other died from a torn subhepatic vein. The 13 survivors did not develop any evidence of malignancy during follow-up (median 50 months). Symptoms from the ectopic secretion resolved after removal of the tumor. Immunohistochemistry was performed and was positive in eight tumors: five ACTH, three calcitonins, and one VIP. CONCLUSIONS: Most pheochromocytomas with ectopic secretion are neither malignant nor familial. Most ectopic hormone-secreting pheochromocytoma cause hypercortisolemia. Patients with a pheochromocytoma should be worked up for ectopic hormones, because removal of the pheochromocytoma resolves those symptoms. Associated cortisol secretion needs careful attention.
PubMed-ID: 22362045
http://dx.doi.org/10.1007/s00268-012-1488-1
Retroperitoneal Adrenal-Sparing Surgery for the Treatment of Cushing's Syndrome Caused by Adrenocortical Adenoma: 8-Year Experience With 87 Patients.
World J Surg, 36(5):1182-8.
He HC, Dai J, Shen ZJ, Zhu Y, Sun FK, Shao Y, Zhang RM, Wang HF, Rui WB, Zhong S. 2012.
BACKGROUND: The objective of this study was to present our 8-year experience with partial adrenalectomy via the retroperitoneal approach for the treatment of Cushing's adenoma. METHODS: A total of 93 patients who underwent adrenal surgery for Cushing's adenoma from March 2003 to December 2010 were enrolled in this study. Preoperative, intraoperative, and postoperative variables were reviewed from the database. Student's t test was used to analyze the continuous data, and the chi(2) test was used to analyze the categoric data. A value of p < 0.05 was considered statistically significant. RESULTS: Adrenal-sparing surgery was performed in 87 cases (31 by open surgery, 56 by retroperitoneal laparoscopy). Six patients underwent open/laparoscopic total adrenalectomy because of recurrent disease or a large size. The cure rate in our series was 97.8%. Hypertension resolved in 34 of 64 patients (53.1%), diabetes in 7 of 27 patients (25.9%) and obesity in 28 of 48 patients (58.3%). One patient died during the postoperative period. The intraoperative complication rate for the open surgery group was significantly higher than that for the retroperitoneal laparoscopy group (9.1 vs. 1.7%). CONCLUSIONS: The retroperitoneal approach is reliable and safe for treating Cushing's syndrome. The laparoscopic technique can decrease the prevalence of intraoperative complications. Retroperitoneal laparoscopic partial adrenalectomy can be performed with extremely low morbidity and achieves an excellent outcome, although death may occur during the postoperative period in high-risk patients. Postoperative management plays an important role in the surgical treatment of Cushing's syndrome.
PubMed-ID: 22382766
http://dx.doi.org/10.1007/s00268-012-1509-0
Robotic Versus Laparoscopic Resection of Large Adrenal Tumors.
Ann Surg Oncol, 19(7):2288-94.
Agcaoglu O, Aliyev S, Karabulut K, Mitchell J, Siperstein A, Berber E. 2012.
BACKGROUND: Although recent studies have shown the feasibility and safety of robotic adrenalectomy, an advantage over the laparoscopic approach has not been demonstrated. Our hypothesis was that the use of the robot would facilitate minimally invasive resection of large adrenal tumors. METHODS: Adrenal tumors>/=5 cm resected robotically were compared with those removed laparoscopically from a prospective institutional review board-approved adrenal database. Clinical and perioperative parameters were analyzed using t and chi-square tests. All data are expressed as mean+/-standard error of mean. RESULTS: There were 24 patients with 25 tumors in the robotic group and 38 patients with 38 tumors in the laparoscopic group. Tumor size was similar in both groups (6.5+/-0.4 [robotic] vs 6.2+/-0.3 cm [laparoscopic], P=.661). Operative time was shorter for the robotic versus laparoscopic group (159.4+/-13.4 vs 187.2+/-8.3 min, respectively, P=.043), while estimated blood loss was similar (P=.147). The conversion to open rate was less in the robotic (4%) versus the laparoscopic (11%) group; P=.043. Hospital stay was shorter for the robotic group (1.4+/-0.2 vs 1.9+/-0.1 days, respectively, P=.009). The 30-day morbidity was 0 in robotic and 2.7% in laparoscopic group. Pathology was similar between groups. CONCLUSIONS: Our study shows that the use of the robot could shorten operative time and decrease the rate of conversion to open for adrenal tumors larger than 5 cm. Based on our favorable experience, robotic adrenalectomy has become our preferred minimally invasive surgical approach for removing large adrenal tumors.
PubMed-ID: 22396002
http://dx.doi.org/10.1245/s10434-012-2296-4
The Adrenal Vein Sampling International Study (AVIS) for Identifying the Major Subtypes of Primary Aldosteronism.
J Clin Endocrinol Metab, 97(5):1606-14.
Rossi GP, Barisa M, Allolio B, Auchus RJ, Amar L, Cohen D, Degenhart C, Deinum J, Fischer E, Gordon R, Kickuth R, Kline G, Lacroix A, Magill S, Miotto D, Naruse M, Nishikawa T, Omura M, Pimenta E, Plouin PF, Quinkler M, Reincke M, Rossi E, Rump LC, Satoh F, Schultze KL, Seccia TM, Stowasser M, Tanabe A, Trerotola S, Vonend O, Widimsky J, Jr., Wu KD, Wu VC, Pessina AC. 2012.
CONTEXT: In patients who seek surgical cure of primary aldosteronism (PA), The Endocrine Society Guidelines recommend the use of adrenal vein sampling (AVS), which is invasive, technically challenging, difficult to interpret, and commonly held to be risky. OBJECTIVE: The aim of this study was to determine the complication rate of AVS and the ways in which it is performed and interpreted at major referral centers. DESIGN AND SETTINGS: The Adrenal Vein Sampling International Study is an observational, retrospective, multicenter study conducted at major referral centers for endocrine hypertension worldwide. PARTICIPANTS: Eligible centers were identified from those that had published on PA and/or AVS in the last decade. MAIN OUTCOME MEASURE: The protocols, interpretation, and costs of AVS were measured, as well as the rate of adrenal vein rupture and the rate of use of AVS. RESULTS: Twenty of 24 eligible centers from Asia, Australia, North America, and Europe participated and provided information on 2604 AVS studies over a 6-yr period. The percentage of PA patients systematically submitted to AVS was 77% (median; 19-100%, range). Thirteen of the 20 centers used sequential catheterization, and seven used bilaterally simultaneous catheterization; cosyntropin stimulation was used in 11 centers. The overall rate of adrenal vein rupture was 0.61%. It correlated directly with the number of AVS performed at a particular center (P = 0.002) and inversely with the number of AVS performed by each radiologist (P = 0.007). CONCLUSIONS: Despite carrying a minimal risk of adrenal vein rupture and at variance with the guidelines, AVS is not used systematically at major referral centers worldwide. These findings represent an argument for defining guidelines for this clinically important but technically demanding procedure.
PubMed-ID: 22399502
http://dx.doi.org/10.1210/jc.2011-2830
Adrenalectomy Improves Outcomes of Selected Patients With Metastatic Carcinoma.
World J Surg, 36(6):1400-5.
Vazquez BJ, Richards ML, Lohse CM, Thompson GB, Farley DR, Grant CS, Huebner M, Moreno J. 2012.
BACKGROUND: Indications and survival benefit for adrenalectomy (ADX) in the setting of metastasis are not clearly defined. We aimed to determine which patients with primary malignancies may benefit from ADX performed for metastasis. Mayo Clinic institutional outcomes in patients with metastatic disease to the adrenal(s) treated by adrenalectomy were compared to stage-matched historical controls from the Surveillance Epidemiology and End Results (SEER) database. METHODS: A retrospective review (1992-2010) was conducted to identify patients treated with ADX for metastatic cancer at Mayo Clinic, Rochester. Associations of clinical, surgical, and pathologic features with overall survival (OS) were evaluated using Cox proportional regression models. OS for those treated with ADX was compared with that for SEER database stage-matched patients who underwent primary resection without resection of distant disease using log-rank tests. RESULTS: A total of 166 patients underwent ADX for metastatic primaries involving the kidney 60, lung 24, sarcoma 19, colon 15, pancreas 13, and other-35. Patients with sarcoma and kidney, lung, and pancreatic tumors who underwent ADX had better OS at 1, 2, and 3 years than did the SEER-matched controls. Respectively, the rates were for sarcoma (100, 93, 86% vs. 57, 36, 30%), kidney (86, 80, 72% vs. 55, 37, 27%), lung (91, 69, 52% vs. 52, 34, 25%), and pancreas (79, 56, 45% vs. 33, 20, 12%). Univariate analysis identified primary diagnosis <2 years before ADX, other distant site, pancreatic primary, palliative operation, and persistent disease as risk factors for death. CONCLUSIONS: An aggressive surgical approach results in improved OS in patients with metastatic disease arising from soft tissues, kidney, lung, and pancreas. Other tumors may benefit, but larger study cohorts are needed for a meaningful comparison.
PubMed-ID: 22411083
http://dx.doi.org/10.1007/s00268-012-1506-3
TMEM127 Screening in a Large Cohort of Patients With Pheochromocytoma and/or Paraganglioma.
J Clin Endocrinol Metab, 97(5):E805-E809.
Abermil N, Guillaud-Bataille M, Burnichon N, Venisse A, Manivet P, Guignat L, Drui D, Chupin M, Josseaume C, Affres H, Plouin PF, Bertherat J, Jeunemaitre X, Gimenez-Roqueplo AP. 2012.
CONTEXT: TMEM127 is a novel pheochromocytoma (PCC) susceptibility gene. OBJECTIVES: Our aim was to clearly determine the indications for TMEM127 genetic testing in patients with PCC and/or paraganglioma (PGL). PATIENTS AND METHODS: Germline DNA from 642 unrelated patients who did not carry mutations in major PCC susceptibility genes was analyzed. Five hundred fifty-nine patients were affected by PCC, 72 by PGL (22 with head and neck and 50 with thoracic or abdominal location), and 11 by both PCC and PGL. Analysis of the TMEM127 gene was performed by direct sequencing and quantitative multiplex PCR of short fluorescent fragments. RESULTS: In our cohort six mutations (0.9%) were identified. Three of them (p.Ala47Asp, p.Gln64HisfsX18, p.Tyr164X) were found in patients exhibiting clinical criteria for a hereditary disease (young age at diagnosis, bilateral PCC, or family history). The three others (p.Gln157X, p.Val68SerfsX13, p.Val90Met) were detected in patients with an apparently sporadic presentation. No mutation was found among patients with PGL, and no large chromosomal rearrangement spanning the TMEM127 gene was detected. CONCLUSIONS: Our results combined with the two previous studies suggest that direct sequencing of TMEM127 should be considered, after a negative screening of VHL, RET, SDHB, and SDHD genes, in patients with PCC.
PubMed-ID: 22419703
http://dx.doi.org/10.1210/jc.2011-3360
[Preoperative Alpha-Receptor Block in Patients With Pheochromocytoma? Against]
Praoperative Alpha-Rezeptoren-Blockade Beim Phaochromozytom? - Kontra.
Chirurg, 83(6):551-4.
Groeben H. 2012.
Perioperative mortality regarding the resection of catecholamine-producing tumors has been markedly improved. This improvement has been attributed to the preoperative treatment with alpha-receptor blocking agents. An alpha-receptor block is still recommended prior to the resection of pheochromocytoma or paraganglioma. However, the effect has never been tested in a randomized clinical trial. Despite an assumed effective alpha-receptor block, many centers report systolic blood pressure increases beyond 200 mmHg. Out of 200 consecutive resections of catecholamine-producing tumors, 73 patients without an alpha-receptor blockade were treated. There was no significant difference in the maximum systolic blood pressure or in the incidence of hypertensive episodes. There was no correlation between the individual dose of phenoxybenzamine and the maximum blood pressure. Overall it can be concluded that with the improvement of surgical techniques, diagnostic tools and highly effective short acting substances to control hemodynamics intraoperatively, the question must be raised whether a time-consuming, unreliable pretreatment burdened with significant side effects is still required.
PubMed-ID: 22437284
http://dx.doi.org/10.1007/s00104-011-2196-3
[Preoperative Alpha-Adrenoceptor Block in Asymptomatic Pheochromocytoma? Pro]
Praoperative Alpha-Rezeptoren-Blockade Beim Asymptomatischen Phaochromozytom? Pro.
Chirurg, 83(6):546-50.
Bracker L, Rath S, Dralle H, Bucher M. 2012.
In approximately 90% of all cases a pheochromocytoma causes sustained or paroxysmal hypertension. During surgical resection tumor manipulation can lead to excessive catecholamine release with the risk of life-threatening complications. Since the early 1950s a preoperative medical treatment with an alpha-adrenoceptor blocking agent has been successfully administered for prevention of hemodynamic instability but not all pheochromocytomas are associated with hypertension. Currently the discovery of asymptomatic pheochromocytomas is more frequent than in the time prior to modern imaging techniques (computed tomography, magnetic resonance imaging). There is little information about this type of pheochromocytoma in the literature. This article discusses the question if preoperative alpha-adrenoceptor block is also indicated in asymptomatic pheochromocytomas based on the current literature.
PubMed-ID: 22466760
http://dx.doi.org/10.1007/s00104-011-2195-4
Is Biochemical Screening for Pheochromocytoma in Adrenal Incidentalomas Expressing Low Unenhanced Attenuation on Computed Tomography Necessary?
J Clin Endocrinol Metab, 97(6):2077-83.
Sane T, Schalin-Jantti C, Raade M. 2012.
OBJECTIVE: Pheochromocytomas are characterized by a high attenuation value on unenhanced computed tomography (CT). It is not known whether pheochromocytoma could be ruled out as a cause of adrenal incidentalomas on the basis of unenhanced attenuation values only. DESIGN: We retrospectively evaluated the outcome of routine biochemical screening for pheochromocytoma in a series of adrenal incidentalomas in relationship to the unenhanced attenuation values on CT. METHODS: An unenhanced CT was available in 174 of 184 patients with 214 adrenal incidentalomas. All patients were screened for pheochromocytoma with 24-h urinary metanephrines and normetanephrines and for hypercortisolism (1 mg dexamethasone test and ACTH). Hypertensive patients were screened for aldosterone overproduction (aldosterone to renin ratio and 24 h urinary aldosterone). The results were compared between incidentalomas with high [>/=10 Hounsfield units (HU)] and low (<10 HU) unenhanced attenuation values. RESULTS: One hundred forty-six incidentalomas in 115 patients had an unenhanced HU less than 10. None of these patients had elevated 24-h fractionated urinary metanephrines or normetanephrines suggesting pheochromocytoma. Sixty-eight incidentalomas in 59 patients had an unenhanced HU of 10 or greater, and nine (15.2%) of these patients had surgically and histologically verified pheochromocytoma. Incidentalomas with a HU of 10 or greater were significantly larger (2.6 +/- 1.5 vs. 2.3 +/- 1.2 cm; P < 0.001), more often functional (27.9 vs. 8.9%, P < 0.001), and more often operated (44.1 vs. 10.2%; P < 0.001) than those with a Hounsfield unit less than 10. CONCLUSION: The results of this study indicate that routine biochemical screening of pheochromocytoma in small homogenous adrenal incidentalomas characterized by an unenhanced Hounsfield unit value less than 10 HU may not be necessary.
PubMed-ID: 22492870
http://dx.doi.org/10.1210/jc.2012-1061
A Comparative Study of the Transperitoneal and Posterior Retroperitoneal Approaches for Laparoscopic Adrenalectomy for Adrenal Tumors.
Ann Surg Oncol, 19(8):2629-34.
Lee CR, Walz MK, Park S, Park JH, Jeong JS, Lee SH, Kang SW, Jeong JJ, Nam KH, Chung WY, Park CS. 2012.
BACKGROUND: Laparoscopic adrenalectomy is considered the gold standard for the surgical treatment of small adrenal tumors. However, several approach routes, such as the transperitoneal (TP), lateral retroperitoneal, and the posterior retroperitoneal (PR) approaches are being used based on surgeon's preference. The PR approach has several benefits compared with the others. Recently, the authors used the PR approach to treat several adrenal tumors and here describe the methods used in detail and the preliminary results obtained. METHODS: From January 2009 to July 2010, 58 patients underwent adrenalectomy. Open adrenalectomy and robotic adrenalectomy were performed in 5 and 10 patients. Also, 43 patients underwent laparoscopic adrenalectomy, and the TP and PR approaches were used in 26 and 17 patients, respectively. Clinicopathologic data and surgical outcomes were evaluated and compared retrospectively. RESULTS: There were no significant differences between the TP and PR groups in terms of age, sex, BMI, lesion side, volume of blood loss, or tumor size (3.86 +/- 3.83 in TP approach, 2.64 +/- 1.61 in PR approach). Mean operative time and average oral intake time using the PR approach were shorter than for the TP approach. Less analgesia use was required in patients who underwent PR approach. CONCLUSIONS: This study shows that posterior retroperitoneoscopic adrenalectomy is a safe procedure and the operative time is comparable to transperitoneoscopic adrenalectomy. The use of the PR approach for small adrenal tumor can provide very favorable surgical outcomes compared with the TP approach.
PubMed-ID: 22526902
http://dx.doi.org/10.1245/s10434-012-2352-0
Resection of Adrenocortical Carcinoma Liver Metastasis: Is It Justified?
Ann Surg Oncol, 19(8):2643-51.
Gaujoux S, Al-Ahmadie H, Allen PJ, Gonen M, Shia J, D'Angelica M, Dematteo R, Fong Y, Blumgart L, Jarnagin WR. 2012.
BACKGROUND: Adrenocortical carcinoma (ACC) liver metastases (LM) represent a therapeutic challenge, and it is unclear whether resection is justified. This study assesses long-term outcome and prognostic factors after liver resection for metastatic ACC. METHODS: Patients who underwent resection of ACC LM were identified from institutional databases. Recurrence, survival, and tumor characteristics, including beta-catenin and TP53 status based on immunohistochemistry and sequencing, were reviewed. The prognostic value of variables was assessed with log-rank test for univariate analysis and Cox proportional hazard models for multivariate analysis. RESULTS: From 1978 to 2009, 28 patients (20 females; median age, 45 years), including 11 with synchronous metastasis and 3 with extrahepatic metastasis, underwent resection for ACC LM (major hepatectomy in 61%). Postoperative mortality was nil and morbidity 55%. On pathological examination, tumors were multiple in 68%, with a median size of 43 mm, and resections were R0, 1, and 2 in 59%, 33%, and 7%, respectively. All 28 patients developed recurrent disease, which was treated surgically in 11, including repeat hepatectomy in 4. Of the 15 patients with adequate tissue for analysis, beta-catenin immunostaining was positive in 7, with 4 corresponding CTNNB1 mutations associated with decreased survival; p53 staining was positive in 5 (4 with corresponding TP53 mutations). The median disease-free and overall survival after hepatectomy was 7 and 31.5 months, respectively, with a 5-year survival of 39%. In multivariate analysis, nonfunctional tumor and surgical treatment of recurrence were independent predictors of good outcome. CONCLUSIONS: In selected patients with ACC LM, resection is associated with long-term survival and is, therefore, justified but rarely curative.
PubMed-ID: 22526905
http://dx.doi.org/10.1245/s10434-012-2358-7
[Adrenal Gland Surgery: Tailored Approach]
Nebennierenchirurgie: "Tailored Approach".
Chirurg, 83(6):509-10.
Dralle H. 2012.
PubMed-ID: 22580724
http://dx.doi.org/10.1007/s00104-011-2190-9
[Function-Preserving Adrenalectomy for Adrenal Tumors]
Funktionserhaltende Adrenalektomie Bei Nebennierentumoren.
Chirurg, 83(6):519-27.
Brauckhoff M, Dralle H. 2012.
Organ preserving resection (subtotal adrenalectomy) or adrenocortical autotransplantation can preserve adrenocortical stress capacity in bilateral adrenal surgery. After adrenocortical autotransplantation approximately 30% of patients do not need exogenous steroids. Organ preserving surgery avoids steroid supplementation in more than 80% of cases. After organ preserving resections in secondary or familial diseases, however, there is a relevant risk of recurrent disease: the rate of ipsilateral recurrence in familial pheochromocytoma is approximately 20% during a follow-up of 20 years. Routine administration of exogenous steroids should be avoided after subtotal adrenalectomy as functional restitution of the residual tissue might be disturbed. Approximately 80% of patients, however, present with impaired adrenocortical stress capacity directly after surgery. Within a few weeks some 80% of patients show a sufficient functional restitution of the adrenocortical stress capacity. Organ preserving adrenal surgery should be performed endoscopically. The adrenal remnant should not be devascularized; the adrenal vein, however, can be divided without functional consequences. About one third of a normal adrenal gland usually provides sufficient adrenocortical function.
PubMed-ID: 22580725
http://dx.doi.org/10.1007/s00104-011-2192-7
[German Adrenocortical Carcinoma Registry. Surgical Therapy Results and Follow-Up Treatment]
Deutsches Nebennierenrindenkarzinom-Register. Chirurgische Therapieergebnisse Und Nachbehandlung.
Chirurg, 83(6):528-35.
Reibetanz J, Kroiss M, Deutschbein T, Fenske W, Gasser M, Jurowich C, Germer CT, Allolio B, Fassnacht M. 2012.
Adrenocortical carcinoma (ACC) is a highly aggressive endocrine disease with an incidence of 1-2 cases per million population per year. Due to the low incidence of ACC knowledge concerning the surgical management is mainly based on retrospective studies or recommendations of isolated experts. Cancer databases, such as the German ACC registry are prerequisite to collect and evaluate clinical data from a large number of patients. For non-metastatic tumor stages, complete tumor resection is the only treatment with curative intent. Open surgery remains the recommended approach for ACC. However, in small tumors with uncertain malignancy a laparoscopic resection by an expert surgeon can be considered. A loco-regional lymphadenectomy should be part of the primary surgical treatment of ACC. Tumor recurrence is common even after an apparently complete primary resection. Therefore, based on the individual risk (tumor size, resection status, proliferation index) adjuvant mitotane treatment is recommended in most patients. Patients with low-risk should be included in the ADIUVO trial. In case of tumor relapse indications for a reoperation should be strongly considered, especially when the time interval since the primary surgery is long (> 12 months) and a complete resection of the recurrent disease seems to be feasible.
PubMed-ID: 22585346
http://dx.doi.org/10.1007/s00104-011-2193-6
[Minimally Invasive Adrenal Gland Surgery. Transperitoneal or Retroperitoneal Approach?]
Minimal-Invasive Nebennierenchirurgie. Transperitonealer Oder Retroperitonealer Zugang?
Chirurg , 83(6):536-45.
Walz MK. 2012.
Currently adrenal gland surgery can be performed by a variety of laparoscopic and retroperitoneoscopic approaches. Of particular importance are the lateral laparoscopic and posterior retroperitoneoscopic approaches. Comparative studies of transperitoneal and retroperitoneal adrenalectomy demonstrate heterogeneous results. Nevertheless, retroperitoneal techniques may offer less postoperative pain and faster recovery. All these minimally invasive techniques are safe and reliable and have replaced open approaches in most cases.
PubMed-ID: 22653137
http://dx.doi.org/10.1007/s00104-011-2194-5

NET
Meta-Analyses
Neuroendocrine ACTH-Producing Tumor of the Thymus--Experience With 12 Patients Over 25 Years.
J Clin Endocrinol Metab, 97(7):2223-30.
Neary NM, Lopez-Chavez A, Abel BS, Boyce AM, Schaub N, Kwong K, Stratakis CA, Moran CA, Giaccone G, Nieman LK. 2012.
CONTEXT: ACTH-producing neuroendocrine tumor (NET) of the thymus is a rare cause of Cushing's syndrome (CS). The literature consists mainly of isolated case reports. PATIENTS: We studied 12 cases (eight males and four females) diagnosed between 1986 and 2010 with CS and thymic NET who underwent surgical resection. MAIN OUTCOME MEASURES: We measured time from onset of CS to diagnosis of thymic NET, tumor size, histological grade, time to recurrence, and survival and performed a meta-analysis of other published cases of CS associated with thymic NET. RESULTS: Eleven of 12 patients presented with classic features of CS at a median age of 21 yr (range, 7-51). Four were children. The 24-h urine free cortisol was greater than 16-fold of normal, and biochemical testing was consistent with ectopic ACTH production in all 11. Another patient presenting with pulmonary embolus had a thymic mass and was later diagnosed with CS. All patients underwent thymectomy, and nine of 10 tumors exhibited positive ACTH immunochemistry. Median tumor diameter was 5 cm (range, 1-11.5). Six patients recurred 20-28 months after surgery with metastases to mediastinal lymph nodes (n = 5), bone (n = 5), liver (n = 1), parotid gland (n = 1), and breast (n = 1). Four of five patients treated with radiation therapy also received chemotherapy. All recurrent patients received ketoconazole; four later underwent bilateral adrenalectomy. Six recurrent patients died 22-90 months (median, 57) after thymectomy. At last review, six patients were alive 14-90 months (median, 49) after thymectomy. These data are similar to those from the meta-analysis. CONCLUSIONS: Thymic ACTH-producing NET is an aggressive disease that should be considered in CS with ectopic ACTH secretion, particularly in younger patients.
PubMed-ID: 22508705
http://dx.doi.org/10.1210/jc.2011-3355
Randomized controlled trials
- None -
Other Articles
Head and Neck Paragangliomas: Report of 175 Patients (1989-2010).
Head Neck, 34(5):632-7.
Papaspyrou K, Mewes T, Rossmann H, Fottner C, Schneider-Raetzke B, Bartsch O, Schreckenberger M, Lackner KJ, Amedee RG, Mann WJ. 2012.
BACKGROUND: Attention of the otorhinolaryngologist needs to be drawn to the versatile aspects of head and neck paragangliomas (PGLs). METHODS: This study is a retrospective, nonrandomized clinical study of all 175 individuals with PGLs treated in our department between 1989 and 2010. A genetic analysis was performed on 86 patients. RESULTS: The 175 patients presented 224 head and neck PGLs as well as 2 thyroid papillary carcinomas. Genetic analysis resulted in 1 patient positive for a von Hippel-Lindau (VHL) gene mutation and 34 for succinate dehydrogenase (SDH) gene mutations (22 SDHD, 7 SDHC, and 5 SDHB), 12 of the latter carrying a novel mutation. Thirty-three patients (18.9%) had multiple PGLs and 11 patients (6.3%) had a malignant paraganglioma. SDH-mutation carriers had multiple tumors in 64.7% and malignant paragangliomas in 20.6%. CONCLUSIONS: Multifocal occurrence, potential malignancy, genetic aspects, possible coincidence of thyroid carcinoma, and hormone production have to be considered in patients with head and neck PGLs.
PubMed-ID: 21692132
http://dx.doi.org/10.1002/hed.21790
Type I Gastric Carcinoids: a Prospective Study on Endoscopic Management and Recurrence Rate.
Neuroendocrinology, 95(3):207-13.
Merola E, Sbrozzi-Vanni A, Panzuto F, D'Ambra G, Di GE, Pilozzi E, Capurso G, Lahner E, Bordi C, Annibale B, Delle FG. 2012.
BACKGROUND: Type I gastric carcinoids (TIGCs) are neuroendocrine neoplasms arising from enterochromaffin-like cells in atrophic body gastritis. Data regarding their evolution in prospective series are scarce, thus treatment and follow-up are not codified. Our aim was to evaluate clinical outcome and recurrence in TIGCs managed by endoscopic approach. METHODS: 33 patients (24 females; median age 65 years, range 23-81) were included and managed through endoscopic follow-up every 6-12 months, with lesion removal and multiple gastric biopsies. Baseline clinical and histological features were analyzed as risk factors by Cox regression. RESULTS: At diagnosis, 7 tumors were intramucosal carcinoids and 26 were polyps (median diameter 5 mm, range 2-20), multiple in 17 patients. Associated severe atrophy was present in 21 cases (63.6%), while mild atrophy was found in 6 cases (18.2%). During a 46-month median follow-up, survival was 100% and no metastases occurred. One patient developed a less-differentiated carcinoid that was radically treated by surgery. 21 patients (63.6%) had recurrence after a median of 8 months, 14 of these (66.6%) had a second recurrence after a median of 8 months following the previous carcinoid removal. Median recurrence-free survival was 24 months. Neither clinical nor biochemical recurrence-predicting factors were found. CONCLUSIONS: Although about 60% of TIGCs had recurrence after endoscopic resection, endoscopic management may be considered safe and effective.
PubMed-ID: 21811050
http://dx.doi.org/10.1159/000329043
Long-Term Results of Surgery for Small Intestinal Neuroendocrine Tumors at a Tertiary Referral Center.
World J Surg, 36(6):1419-31.
Norlen O, Stalberg P, Oberg K, Eriksson J, Hedberg J, Hessman O, Janson ET, Hellman P, Akerstrom G. 2012.
BACKGROUND: Small intestinal neuroendocrine tumors (SI-NETs) are uncommon, with an annual incidence of about 1 per 100,000 individuals. The primary tumor (PT) is generally small, but nevertheless the majority of patients have mesenteric lymph node metastases and liver metastases at diagnosis. Our aim was to identify prognostic factors for survival and to evaluate outcome after surgery in SI-NET patients. MATERIAL AND METHODS: We included 603 consecutive patients (325 men; age at diagnosis 63 +/- 11 years [mean +/- SD]) with histopathologically verified SI-NET, who were diagnosed between 1985 and 2010. Hospital charts were reviewed and were scrutinized for carcinoid heart disease (CHD), flush and/or diarrhea, proliferation by Ki-67 index, mesenteric lymph node metastases (m.lgllm), distant abdominal lymph node metastases (da.lgllm), liver tumor load (LTL), extra-abdominal metastases (EAM), locoregional resective surgery, as well as debulking of LTL, and adverse events after surgery. RESULTS: Median overall survival (OS) was 8.4 years; 5-year OS was 67%, and 5-year relative survival was 74%. Independent prognostic factors by univariate and multivariate analysis were age at diagnosis, CHD, m.lgllm, da.lgllm, LTL, EAM, peritoneal carcinomatosis (PC), and proliferation. Locoregional resective surgery was associated with increased survival on crude and multivariate analysis. The 30-day mortality in our institution after initial locoregional resective surgery was 0.5% (1/205). CONCLUSIONS: For the first time, m.lgllm and da.lgllm, LTL, PC, and EAM are demonstrated to be independent prognostic factors by multivariate analysis. Locoregional removal of the PT/m.lgllm. was a positive prognostic factor by crude and adjusted analysis and may influence survival.
PubMed-ID: 21984144
http://dx.doi.org/10.1007/s00268-011-1296-z
Survival Impact of Malignant Pancreatic Neuroendocrine and Islet Cell Neoplasm Phenotypes.
J Surg Oncol, 105(6):595-600.
Roland CL, Bian A, Mansour JC, Yopp AC, Balch GC, Sharma R, Xie XJ, Schwarz RE. 2012.
BACKGROUND: The low incidence of malignant "functional" (F) or "nonfunctional" (NF) neuroendocrine islet cell tumors (ICTs) of the pancreas represents a challenge to precise post-therapeutic survival prediction. This study examined the survival impact of malignant pancreatic ICT morphologic subtypes. METHODS: A pancreatic ICT data set was created from a US-based population database from 1980-2004. Prognostic factors with survival impact and relationships between surgical therapy and overall survival (OS) were analyzed. RESULTS: There were 2,350 individuals with malignant ICTs. Histologic subtypes included carcinoid tumors, islet cell carcinomas, neuroendocrine carcinomas, and malignant gastrinomas, insulinomas, glucagonomas, or VIPomas. There was no difference in resection rates between FICTs and NFICTs (23% vs. 20%, P = ns). Median OS was 30 months, with group differences ranging from NE carcinomas (21) to VIPomas (96; P < 0.0001). Median OS of resected versus unresected FICTs was 172 versus 37 months, while that of NFICTs was 113 versus 18 months (P < 0.0001). Compared to neuroendocrine carcinomas, hazard ratios were: VIPomas 0.48, gastrinomas 0.65, carcinoid tumors 0.76, insulinomas 0.84, glucagonomas 0.93, and islet cell carcinomas 1.0. CONCLUSIONS: When controlled for other established prognostic parameters, histopathologic subtype assignment of pancreatic ICTs affects survival prediction. Resection is associated with superior survival for all tumor types.
PubMed-ID: 22006521
http://dx.doi.org/10.1002/jso.22118
Prognostic Relevance of Survivin in Pancreatic Endocrine Tumors.
World J Surg, 36(6):1411-8.
Ekeblad S, Lejonklou MH, Stalberg P, Skogseid B. 2012.
BACKGROUND: Better prognostic markers are needed for pancreatic endocrine tumors. Survivin is an apoptosis inhibitor that is suggested to have a negative prognostic impact in several tumor types. Contradictory data exist, especially regarding the significance of a nuclear versus cytoplasmic location of survivin. The prognostic relevance of nuclear and cytoplasmic survivin expression in pancreatic endocrine tumors-controlled for the tumor Ki-67 index, World Health Organization classification, and TNM stage-was investigated. METHODS: A total of 111 patients treated at a tertiary referral center were retrospectively evaluated. Clinical data were gathered from medical records. Immunohistochemistry for survivin and Ki-67 was performed on paraffin-embedded tissue. Univariate and multivariate Cox analyses were performed. RESULTS: Patients with tumors that had <5% survivin-positive nuclei had a mean survival of 225 months [95% confidence interval (CI) 168-281]. The corresponding figure for patients with 5 to 50% survivin-positive tumor cell nuclei was 101 months [95% CI 61-140; hazard ratio (HR) 2.4; P < 0.01) and with >50% survivin-positive nuclei 47 months (95% CI 24-71; HR 4.9; P < 0.001). Nuclear survivin expression in >50% of the tumor cells was an independent marker of a poor prognosis (HR 5.7; P < 0.01). Cytoplasmic survivin was not a significant prognostic factor in the multivariate analysis (HR 0.94; P = 0.90). CONCLUSIONS: High expression of nuclear survivin is a significant marker of a poor prognosis in patients with a pancreatic endocrine tumor.
PubMed-ID: 22089920
http://dx.doi.org/10.1007/s00268-011-1345-7
The Novel WHO 2010 Classification for Gastrointestinal Neuroendocrine Tumours Correlates Well With the Metastatic Potential of Rectal Neuroendocrine Tumours.
Neuroendocrinology, 95(4):317-24.
Jernman J, Valimaki MJ, Louhimo J, Haglund C, Arola J. 2012.
BACKGROUND: Approximately 10-15% of gastroenteropancreatic neuroendocrine tumours (NETs, carcinoids) occur in the rectum, some of which are potentially able to metastasize. The new WHO 2010 classification of NETs applies to all gastroenteropancreatic NETs, but no reports have studied its correlation with the prognosis of rectal NETs. PATIENTS AND METHODs: We retrospectively classified 73 rectal NETs according to the novel WHO 2010 and the previous WHO 2000 classifications. The aim was to assess the validity of the classifications in distinguishing indolent rectal NETs from metastasising tumours. RESULTs: Using the WHO 2010 criteria, we identified 61 G1 tumours, none of which had metastasised during follow-up. Of 11 G2 tumours, 9 had shown distant metastases. The only G3 neuroendocrine carcinoma that occurred had been disseminated at initial presentation. CONCLUSION: Our results show that rectal NETs classified as G1 according to the WHO 2010 classification have an indolent clinical course, whereas G2 NETs often metastasise. The WHO 2010 classification of NETs predicts the metastatic potential of rectal NETs better than the WHO 2000 classification.
PubMed-ID: 22327359
http://dx.doi.org/10.1159/000333035
Chromogranin A Is a Reliable Biomarker for Gastroenteropancreatic Neuroendocrine Tumors in an Asian Population of Patients.
Neuroendocrinology, 95(4):344-50.
Chou WC, Hung YS, Hsu JT, Chen JS, Lu CH, Hwang TL, Rau KM, Yeh KY, Chen TC, Sun CF. 2012.
PURPOSE: To evaluate the significance of plasma chromogranin A (CgA) levels in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET) in terms of disease status and treatment responses. MATERIALS AND METHODS: Forty-four GEP-NET patients comprising 15 disease-free patients and 29 patients with active disease, as well as 26 healthy participants were enrolled in this study between April 2010 and April 2011. Clinicopathological factors were collected and serial plasma CgA levels were measured. RESULTS: Plasma CgA levels were significantly higher in GEP-NET patients with active disease than in disease-free patients (p = 0.011) or healthy participants (p = 0.001). No difference in CgA levels was observed in terms of primary tumor location, tumor grade, and functional status in patients with active disease. CgA values at 94 U/l distinguished healthy individuals or disease-free patients from patients with active disease. Sensitivity and specificity rates were 86 and 88%, respectively. CgA levels at 110 U/l differentiated patients without recurrence from those with recurrence, with a sensitivity rate of 100% and a specificity rate of 80%. Patients (5/5, 100%) with stable disease and who showed partial response after treatment had a more than 20% decrease in CgA levels compared with the baseline values. Patients (6/6, 100%) with progressive disease showed a less than 20% decrease or increase in CgA levels. CONCLUSION: The plasma CgA level is a reliable biomarker for GEP-NET. We conclude that changes in CgA levels are associated with disease status and treatment responses.
PubMed-ID: 22343505
http://dx.doi.org/10.1159/000333853
Preoperative Assessment of the Pancreas in Multiple Endocrine Neoplasia Type 1.
World J Surg, 36(6):1375-81.
Lewis MA, Thompson GB, Young WF, Jr. 2012.
BACKGROUND: Many serologic and radiographic modalities are used for monitoring multiple endocrine neoplasia type 1 (MEN 1) patients for pancreaticoduodenal neuroendocrine tumors (PNETs). We compared serum markers and imaging studies obtained preoperatively with the gross pathology and immunohistochemical findings and correlated preoperative testing with postoperative outcome. METHODS: From 2000 to 2008, 52 MEN 1 patients [32 (62%) female; median age = 43 years, range 19-74 years] underwent 56 pancreatic operations [49 (88%) distal pancreatectomies] for suspected PNETs. Preoperative serum markers [human pancreatic polypeptide (HPP), gastrin, and glucagon] and imaging [CT, (111)In pentetreotide scintigraphy, and endoscopic ultrasound (EUS)] were compared to the pathologic findings. Postoperative serum markers and survival were followed. RESULTS: Human pancreatic polypeptide had the highest agreement between an elevated serum level and positive tumor immunostaining (83% vs. 50% agreement for gastrin vs. 67% agreement for glucagon). Preoperative CT had 81% sensitivity and positive predictive value (PPV) of 97% for PNETs. (111)In pentetreotide scintigraphy had 84% sensitivity and PPV of 96%. Preoperative endoscopic ultrasonography (EUS) had 100% sensitivity and PPV, with close correlation (r (s) = 0.93) between the largest lesion seen on EUS and pathology. Median follow-up was 4.3 years (range = 0.1-10.9 years). Overall survival was 89% at 5-year follow-up. CONCLUSIONS: Our study substantiates EUS as providing the highest preoperative sensitivity and PPV in assessing the presence of PNETs in MEN 1 patients. CT and octreotide scintigraphy can yield both false-positive and false-negative results. HPP, gastrin, and glucagon were the most commonly measured tumor markers in our series but did not always correlate with immunostaining. With an aggressive surgical approach, satisfactory rates of biochemical improvement and long-term survival were observed.
PubMed-ID: 22382771
http://dx.doi.org/10.1007/s00268-012-1539-7
Pancreatic Neuroendocrine Tumors: Radiographic Calcifications Correlate With Grade and Metastasis.
Ann Surg Oncol, 19(7):2295-303.
Poultsides GA, Huang LC, Chen Y, Visser BC, Pai RK, Jeffrey RB, Park WG, Chen AM, Kunz PL, Fisher GA, Norton JA. 2012.
BACKGROUND: Studies to identify preoperative prognostic variables for pancreatic neuroendocrine tumor (PNET) have been inconclusive. Specifically, the prevalence and prognostic significance of radiographic calcifications in these tumors remains unclear. METHODS: From 1998 to 2009, a total of 110 patients with well-differentiated PNET underwent surgical resection at our institution. Synchronous liver metastases present in 31 patients (28%) were addressed surgically with curative intent. Patients with high-grade PNET were excluded. The presence of calcifications in the primary tumor on preoperative computed tomography was recorded and correlated with clinicopathologic variables and overall survival. RESULTS: Calcifications were present in 16% of patients and were more common in gastrinomas and glucagonomas (50%), but never encountered in insulinomas. Calcified tumors were larger (median size 4.5 vs. 2.3 cm, P=0.04) and more commonly associated with lymph node metastasis (75 vs. 35%, P=0.01), synchronous liver metastasis (62 vs. 21%, P<0.01), and intermediate tumor grade (80 vs. 31%, P<0.01). On multivariate analysis of factors available preoperatively, calcifications (P=0.01) and size (P<0.01) remained independent predictors of lymph node metastasis. Overall survival after resection was significantly worse in the presence of synchronous liver metastasis (5-year, 64 vs. 86%, P=0.04), but not in the presence of radiographic calcifications. CONCLUSIONS: Calcifications on preoperative computed tomography correlate with intermediate grade and lymph node metastasis in well-differentiated PNET. This information is available preoperatively and supports the routine dissection of regional lymph nodes through formal pancreatectomy rather than enucleation in calcified PNET.
PubMed-ID: 22396008
http://dx.doi.org/10.1245/s10434-012-2305-7
Neuroendocrine Tumours of the Ampulla of Vater: Clinico-Pathological Features, Surgical Approach and Assessment of Prognosis.
Langenbecks Arch Surg, 397(6):933-43.
Dumitrascu T, Dima S, Herlea V, Tomulescu V, Ionescu M, Popescu I. 2012.
BACKGROUND/AIMS: Neuroendocrine tumours occur very rarely in the ampulla of Vater and their clinical behaviour is unknown. The aim of this study is to assess the clinico-pathological features, surgical approach and prognosis of these patients. METHODS: Six patients with neuroendocrine tumours of the ampulla of Vater treated with curative intent surgery at a single centre were retrospectively analysed. A univariate analysis of potential prognostic factors was also performed (data provided from the present study and literature review). RESULTS: Pancreaticoduodenectomy was curative in all the patients. Overall and disease-free survival rates were significantly better for G1/G2 tumours (p = 0.006 and p = 0.004, respectively). Although frequent, lymph node metastases did not influenced both overall (p = 0.760) and disease-free survival rates (p = 0.745). No significant differences of survival were observed in patients with ENETS stage I/II disease, as compared to ENETS stage III disease (p = 0.169 and p = 0.137, respectively). No differences were observed according to UICC staging system (p = 0.073 and p = 0.177, respectively). Tumours that are less than 2 cm or limited to the ampulla appear to have a better prognosis. CONCLUSION: The WHO 2010 classification appear to accurately predict patient prognosis, while the ENETS or UICC staging systems have a limited value (especially in regard to lymph node metastases). Radical surgery (i.e. pancreaticoduodenectomy with lymphadenectomy) should be the standard approach in most patients with NET of the ampulla of Vater because this procedure removes all the potential tumour-bearing tissue.
PubMed-ID: 22476195
http://dx.doi.org/10.1007/s00423-012-0951-7
Rate of Clinically Significant Postoperative Pancreatic Fistula in Pancreatic Neuroendocrine Tumors.
World J Surg, 36(7):1517-26.
Inchauste SM, Lanier BJ, Libutti SK, Phan GQ, Nilubol N, Steinberg SM, Kebebew E, Hughes MS. 2012.
BACKGROUND: In 2005, the International Study Group of Pancreatic Fistula (ISGPF) developed a definition and grading system for postoperative pancreatic fistula (POPF). The authors sought to determine the rate of POPF after enucleation and/or resection of pancreatic neuroendocrine tumors (PNET) and to identify clinical, surgical, or pathologic factors associated with POPF. METHODS: A retrospective analysis of pancreatic enucleations and resections performed from March 1998 to April 2010. We defined a clinically significant POPF as a grade B that required nonoperative intervention and grade C. RESULTS: One hundred twenty-two patients were identified; 62 patients had enucleations and 60 patients had resections of PNET. The rate of clinically significant POPF was 23.7 % (29/122). For pancreatic enucleation, the POPF rate was 27.4 % (17/62, 14 grade B, 3 grade C). The pancreatic resection group had a POPF rate of 20 % (12/60, 10 grade B, 2 grade C). This difference was not significant (p = 0.4). In univariate analyses, patients in the enucleation group with hereditary syndromes (p = 0.02) and non-insulinoma tumors (p = 0.02) had a higher POPF rate. Patients in the resection group with body mass index (BMI) > 25 (p < 0.01), multiple endocrine neoplasia type 1 (MEN-1; p < 0.01) and those who underwent simultaneous multiple procedures (p = 0.02) had a higher POPF rate. Multivariate analyses revealed that hereditary syndromes were able to predict POPF in the enucleation group, while having BMI > 25 and increasing lesion size were also associated with POPF in the group undergoing resection. CONCLUSIONS: We found a clinically significant POPF rate after surgery in PNET to be 23.7 % with no difference by the type of operation. Our POPF rate is comparable to that reported in the literature for pancreatic resection for other types of tumors. Certain inherited genetic diseases-von Hippel-Lindau disease (VHL) and MEN-1-were associated with higher POPF rates.
PubMed-ID: 22526042
http://dx.doi.org/10.1007/s00268-012-1598-9

GI and General
Meta-Analyses
- None -
Randomized controlled trials
- None -
Other Articles
Cervical and Upper Mediastinal Lymph Node Metastasis From Gastrointestinal and Pancreatic Neuroendocrine Tumors: True Incidence and Management.
J Am Coll Surg, 214(6):1017-22.
Wang YZ, Mayhall G, Anthony LB, Campeau RJ, Boudreaux JP, Woltering EA. 2012.
BACKGROUND: The incidence, clinical importance, and optimal management of cervical and upper mediastinal lymph node metastasis from gastrointestinal and pancreatic neuroendocrine tumors (NETS) are largely unknown. Historically, cervical nodes have been regarded as asymptomatic and ignored. We hypothesized that these lesions have clinical implications and should be removed surgically. STUDY DESIGN: Consecutive (111)In pentetreotide scans (OctreoScan) performed at our institution from May 2008 to October 2010 were reviewed to determine the incidence of cervical and upper mediastinal lymph node metastases among patients with gastrointestinal and pancreatic NETs. The charts of surgically treated patients were reviewed to evaluate the clinical importance of these metastases and the subsequent outcomes of their surgical treatment. RESULTS: A total of 161 NET patients presented with positive OctreoScans. Fourteen patients (8.7%) scanned positive for cervical and upper mediastinal lymph node metastasis. Nine patients underwent surgical exploration; 8 had successful removal of their metastatic nodes. Seven had clinical symptoms that resolved after surgery. CONCLUSIONS: Cervical and upper mediastinal lymph node metastases from gastrointestinal and pancreatic NETs were seen in up to 8.7% of patients. In the past, these metastases were assumed to be insignificant and ignored. Our study clearly demonstrates that most, if not all, such metastases are symptomatic and their clinical implications should not be overlooked. Notably, these metastases can be easily and safely resected using radioguided surgery.
PubMed-ID: 22521444
http://dx.doi.org/10.1016/j.jamcollsurg.2012.02.006
Transoral Robotic Surgery: Role in the Management of Upper Aerodigestive Tract Tumors.
Head Neck, 34(6):886-93.
Genden EM, O'Malley BW, Jr., Weinstein GS, Stucken CL, Selber JC, Rinaldo A, Hockstein NG, Ozer E, Mallet Y, Satava RM, Moore EJ, Silver CE, Ferlito A. 2012.
The toxicity associated with concomitant chemoradiation for the management of laryngeal and pharyngeal carcinoma has been well documented. Minimally invasive surgical techniques offer the potential to extirpate the malignancy as a single-modality therapy and provide essential information that may direct subsequent treatment. In selected patients, radiation doses may be reduced and systemic chemotherapy may be withheld after tumor extirpation. Transoral laser microsurgery has proven effective, although inability to manipulate and suture tissue by this modality limits ablation and reconstruction of extensive defects. Transoral robotic surgery is a relatively new technique that provides several unique advantages, which include a 3-dimensional magnified view, ability to see and work around curves or angles, and the availability of 2 or 3 robotic arms that can be used to reconstruct extensive defects using either local, regional, or free flaps. Preliminary data suggest that transoral robotic surgery may provide a technique for ablation and reconstruction of pharyngeal defects that may be superior to other transoral techniques. It may also provide a means for personalizing therapy for oropharyngeal and supraglottic carcinoma.
PubMed-ID: 22610591
http://dx.doi.org/10.1002/hed.21752
Metastatic Nonfunctioning Pancreatic Neuroendocrine Carcinoma to Liver: Surgical Treatment and Outcomes.
J Am Coll Surg, 215(1):117-24.
Cusati D, Zhang L, Harmsen WS, Hu A, Farnell MB, Nagorney DM, Donohue JH, Que FG, Reid-Lombardo KM, Kendrick ML. 2012.
BACKGROUND: The surgical treatment of metastatic, nonfunctional pancreatic neuroendocrine carcinoma (nPNEC) is not well defined. Existing series are confounded by inclusion of patients with metastatic functional tumors or gastrointestinal carcinoid. Our hypothesis was that the surgical treatment of metastatic nPNEC provides favorable perioperative and oncologic outcomes. STUDY DESIGN: We performed a retrospective review of all patients undergoing surgical treatment of metastatic nPNEC to the liver from 1987 through 2008 at the Mayo Clinic. Data are presented as medians with ranges. RESULTS: Seventy-two patients were identified, with a median age of 57 years (range 28 to 77 years) and median body mass index (BMI) of 26 kg/m(2) (range 18 to 40 kg/m(2)). Operative intent of resection was curative in 39 (54%) or palliative (>/= 90% tumor debulking) in 32 (44%). Median number of tumors treated and median tumor size were 8 (range 1 to 30) and 4.5 cm (range 0.3 to 20 cm), respectively. Tumor grade was 1 or 2 in 97%, and angioinvasion was identified in 55 (76%) patients. Postoperative morbidity and mortality were 50% and 0%, respectively. Among the 72 patients, overall survivals at 1, 5 and 10 years were 97.1%, 59.9%, and 45.0%, respectively. Among the 39 patients with a complete (R0) resection, the 1- and 5-year disease-free survivals were 53.7% and 10.7%, respectively. For patients undergoing debulking of >/= 90% tumor burden, the 1- and 5-year survivals free of progression were 58.1% and 3.5%, respectively. CONCLUSIONS: Surgical treatment of metastatic nPNEC to the liver with curative intent or for palliative >/= 90% debulking provides favorable oncologic outcomes. Despite a high incidence of tumor recurrence, 5-year survival rates are encouraging and appear to justify an aggressive surgical approach in these patients.
PubMed-ID: 22726741
http://dx.doi.org/10.1016/j.jamcollsurg.2012.05.002

Papers of the International Association of Endocrine Surgery – ISW 2011
World J Surgery, Issue 6
Combination of Dexamethasone and Tropisetron Before Thyroidectomy to Alleviate Postoperative Nausea, Vomiting, and Pain: Randomized Controlled Trial.
World J Surg, 36(6):1217-24.
Zhou H, Xu H, Zhang J, Wang W, Wang Y, Hu Z. 2012.
BACKGROUND: Nausea, vomiting, and pain frequently occur after thyoidectomy. Little evidence exists regarding the effects of administrating a combination of dexamethasone and tropisetron to patients undergoing thyroidectomy. We aimed to evaluate the effects of dexamethasone and tropisetron on thyroidectomy outcomes. METHODS: A total of 150 patients undergoing thyroidectomy were included in this prospective randomized, controlled, three-arm study (group D: 8 mg dexamethasone; group T: 5 mg tropisetron; group D+T: 8 mg dexamethasone and 5 mg tropisetron). There were 50 patients in each group. Nausea, vomiting, pain, and the amount of antiemetic and analgesic agents required were recorded 2, 4, 8, 16, 24, 36, and 48 h postoperatively. RESULTS: The complete response rate of nausea and vomiting was significantly higher in group D+T (78%, 39/50), compared with that in group D (58%, 29/50) or group T (66%, 33/50) (P = 0.01). The incidence and severity of nausea in group D+T were significantly lower than in group D and group T, with the difference mainly occurring in the late postoperative period (6-48 h). The severity of postoperative pain was significantly less in the dexamethasone-containing groups (D and D+T groups) than in the tropisetron group. CONCLUSIONS: The combination of dexamethasone and tropisetron offers better prophylaxis for nausea, vomiting, and pain than either drug alone in patients undergoing thyroidectomy, especially during the late period (6-48 h).
PubMed-ID: 22146946
http://dx.doi.org/10.1007/s00268-011-1363-5
Video-Assisted Versus Conventional Total Thyroidectomy and Central Compartment Neck Dissection for Papillary Thyroid Carcinoma.
World J Surg, 36(6):1225-30.
Lombardi CP, Raffaelli M, De CC, Sessa L, Rampulla V, Bellantone R. 2012.
BACKGROUND: Although video-assisted (VA) thyroidectomy emerged as effective treatment for selected patients with papillary thyroid carcinoma (PTC), some concerns remain about obtaining adequate central neck node clearance. We compared patients who underwent VA and conventional total thyroidectomy (TT) and central compartment dissection (CCD) for PTC. METHODS: A total of 52 consecutive patients successfully underwent VA-TT and VA-CCD for PTC (VA group) were compared to 52 controls who underwent conventional TT and CCD (C group) for PTC. RESULTS: The two groups were matched for age (p = 0.75), sex (p = 0.07), and tumor size (p = 1.0). Operating time (p = 0.23), overall postoperative complications (p = 0.41), pT (p = 0.44), and pN (p = 0.84) were similar in the two groups. The mean number of removed nodes was similar (10.6 +/- 4.6 in VA group vs. 12.2 +/- 5.6 in C group) (p = 0.11).Mean postoperative serum thyroglobulin (sTg) off levothyroxine (LT4) suppressive treatment was 3.2 +/- 5.0 ng/ ml in the VA group and 2.6 +/- 7.4 ng/ml in the C-group (P = 0.67). Mean postoperative radioiodine uptake (RAIU) was similar in the two groups (1.5 +/- 1.3 vs. 1.7 +/- 1.3%) (p = 0.49). When pN1a patients alone were considered, no difference was found between the VA group (21 patients) and the controls (24 patients) concerning the mean number of removed nodes (10.3 +/- 4.1 vs. 12.4 +/- 5.6) (p = 0.16), the mean sTg off LT4 (4.4 +/- 6.0 vs. 1.9 +/- 2.7 ng/ml) (p = 0.07) and the mean RAIU (1.9 +/- 1.5 vs. 1.7% +/- 1.3%) (p = 0.63). CONCLUSIONS: The results of VA-TT and CCD in selected cases of PTC appear to be comparable to those of conventional surgery. A longer follow-up and larger series are necessary to draw definitive conclusions concerning longterm outcomes.
PubMed-ID: 22302283
http://dx.doi.org/10.1007/s00268-012-1439-x
A Novel Definition of Extrathyroidal Invasion for Patients With Papillary Thyroid Carcinoma for Predicting Prognosis.
World J Surg, 36(6):1231-40.
Hotomi M, Sugitani I, Toda K, Kawabata K, Fujimoto Y. 2012.
OBJECTIVES: Extrathyroidal invasion is one of the most significant risk factors for patients with papillary thyroid carcinoma (PTC). The purpose of this study was to evaluate a novel definition of extrathyroidal invasion for patients with PTC as a method for predicting a patient's prognosis. METHODS: The prospective study was conducted for consecutive 930 patients with primary PTC who received surgery during 1993-2009. We defined only patients who had preoperative recurrent laryngeal nerve palsy or patients in whom the tumor had invaded to the mucosa of the trachea and/or esophagus as Ex3. Patients with minimal invasion were classified as Ex1, and patients with massive invasion, when we could shave off the tumors, were classified as Ex2. Patients without extrathyroidal invasion were classified as Ex0. RESULTS: Patients classified Ex3 showed significantly shorter disease-free survival (p = 0.03) and disease-specific survival (p = 0.007) than patients classified Ex2. The time to recurrence at resection sites was shorter in patients classified Ex3 than in patients classified Ex2 (p = 0.02). The time to death due to distant metastasis of patients classified Ex3 was significantly shorter than that of patients classified Ex2 (p = 0.02). Within the patients classified Ex3, disease-specific survival of patients with invasion to other nearby structures was shorter than that of patients with invasion to only recurrent laryngeal nerve (p = 0.008). CONCLUSIONS: The degree and site of invasion is an important prognostic factor for PTC. Our novel classification of extrathyroidal invasion is valuable in predicting the prognosis of PTC.
PubMed-ID: 22402972
http://dx.doi.org/10.1007/s00268-012-1518-z
Clinical Features, Treatment, and Long-Term Outcome of Papillary Thyroid Cancer in Children and Adolescents Without Radiation Exposure.
World J Surg, 36(6):1241-6.
Enomoto Y, Enomoto K, Uchino S, Shibuya H, Watanabe S, Noguchi S. 2012.
BACKGROUND: Cancer of the thyroid gland is rare in children and adolescents. A history of neck irradiation is a well-established risk factor for tumor development, and most previous reports focused on cases that were induced by radiation exposure. We present here a retrospective review of the clinical features, treatment, and long-term outcome of children and adolescents with papillary thyroid cancer (PTC) without a history of radiation exposure who were treated at our institution over a period of ~50 years. METHODS: We retrospectively investigated 142 PTC patients without an irradiation history who were younger than 20 years of age when treated from 1961 to 2005 (17 males and 125 females; mean age = 16.3 +/- 2.7 years; follow-up = 21.8 +/- 12.0 years). The clinicopathological results were evaluated using the medical records. Disease-free survival (DFS) and cause-specific survival (CSS) were assessed with the Kaplan-Meier method and compared with the log-rank test. Parametric analyses were performed using Student's t test and nonparametric analyses were performed using the Mann-Whitney U test. RESULTS: At diagnosis, three patients had distant lung metastasis and 33 had gross neck lymph node (LN) metastasis. All patients were treated with surgery (hemi/partial thyroidectomy in 45 patients, subtotal thyroidectomy in 85, total thyroidectomy in 12, no LN dissection in 50, central compartment dissection in 20, and modified radical neck dissection in 72), and postoperative external beam radiation therapy was administered to 59. Postoperative ablative therapy using I(131) was not performed in this series. Recurrence was found for regional LN (n = 25), lung (n = 9), remnant thyroid (n = 5), and others (n = 4). DFS and CSS at 40 years were 74.1 and 97.5%, respectively. DFS was significantly worse in patients aged <16 years with a family history of thyroid cancer, preoperative neck gross LN metastasis, maximum tumor diameter, and extrathyroidal invasion. Preoperative gross neck LN metastasis and distant metastasis at diagnosis were significant factors for CSS. No other factors contributed to DFS and CSS. When the clinical features of children and adolescents were compared, the incidence of preoperative gross neck LN metastasis and distant metastasis at diagnosis and tumors with a maximum diameter >10 mm were significantly higher in the children group than in the adolescent group. DFS was significantly shorter in the children group than in the adolescent group, but no significant difference was found in CSS between these two groups. CONCLUSIONS: The prognosis of PTC in children and adolescents is excellent, regardless of the extent of thyroidectomy and LN dissection. We recommend that only children or adolescents with preoperative gross neck LN metastasis and distant metastasis at diagnosis should be subjected to postoperative ablative therapy.
PubMed-ID: 22411092
http://dx.doi.org/10.1007/s00268-012-1558-4
Prognostic Factors and Treatment Outcomes for Anaplastic Thyroid Carcinoma: ATC Research Consortium of Japan Cohort Study of 677 Patients. 
World J Surg, 36(6):1247-54.
Sugitani I, Miyauchi A, Sugino K, Okamoto T, Yoshida A, Suzuki S. 2012.
BACKGROUND: Anaplastic thyroid carcinoma (ATC) accounts for only 1 to 2% of all thyroid carcinomas, but it is one of the most lethal neoplasms in humans. To date, most findings about ATC have been derived from single-institution studies with limited numbers of cohorts. To obtain further insights into this "orphan disease," we have established a multicenter registry, the ATC Research Consortium of Japan (ATCCJ). We analyzed prognostic factors and treatment outcomes using the large cohort database of the ATCCJ. METHODS: Most of the Japanese centers involved in the treatment of thyroid cancer were invited to join the ATCCJ and have provided information on ATC patients treated between 1995 and 2008. The database includes 677 cases from 38 registered institutions. Survival curves were determined using Kaplan-Meier methods and were compared using the log-rank test. Cox's proportional hazards model was used for multivariate analysis. RESULTS: Clinical varieties of ATC were classified into four types: common type (n = 547); incidental type (n = 29); anaplastic transformation at the neck (n = 95); anaplastic transformation at a distant site (n = 6). The incidental type followed by anaplastic transformation at the neck showed better outcomes than the other types. Anaplastic transformation at a distant site showed the worst outcomes. The 6-month and 1-year cause-specific survival (CSS) rates for common-type ATC were 36 and 18%, respectively. In all, 84 (15%) achieved long-term (>1 year) survival. Multivariate analysis identified age >/=70 years, presence of acute symptoms, leukocytosis (white blood cell count >/=10,000/mm(3)), large tumor >5 cm, T4b tumor, and distant metastasis as significant risk factors for lower survival. CSS rates also differed significantly depending on UICC stages, with 6-month CSSs of 60% for stage IVA, 45% for IVB, and 19% for IVC. For 36 of 69 (52%) stage IVA patients who underwent radical surgery, adjuvant therapies, including radiation therapy (RTX) and chemotherapy (CTX) did not show additional benefit statistically. Conversely, among 242 stage IVB patients, 80 (33%) underwent radical surgery. For those patients, therapies combining RTX with CTX significantly improved CSS. CONCLUSIONS: Long-term survival is possible for selected patients with ATC. To determine the treatment strategy, UICC stage (disease extent) and other prognostic factors (e.g., biologic malignancy grade) should be considered.
PubMed-ID: 22311136
http://dx.doi.org/10.1007/s00268-012-1437-z
Level VI Lymph Node Dissection Does Not Decrease Radioiodine Uptake in Patients Undergoing Radioiodine Ablation for Differentiated Thyroid Cancer.
World J Surg, 36(6):1255-61.
Yoo D, Ajmal S, Gowda S, Machan J, Monchik J, Mazzaglia P. 2012.
BACKGROUND: In patients with well-differentiated thyroid cancer, the incidence of pathologic central compartment lymph node metastases is reported to be approximately 50%. Recently level VI lymph node dissection has been advocated as a means of reducing recurrence rates in these patients, even if there are no clinically apparent nodal metastases. This study investigates whether level VI lymph node dissection decreases the percent radioiodine uptake when patients undergo radioiodine ablation. METHODS: All thyroid cancer patients entered into the endocrine surgery database at a tertiary care center from 2006 to 2010 were reviewed. Those treated with radioactive iodine were analyzed with respect to performance of a central compartment lymph node dissection and the percent uptake of radioiodine ((131)I) on the preablation scan at 72 h. RESULTS: There were 277 patients with well-differentiated thyroid cancer who underwent radioiodine ablation. In all, 75% were female, and the mean age was 47.7 years. A total of 87 patients underwent total thyroidectomy and level VI lymph node dissection (TT + LVIND). The mean number of level VI nodes resected was 6 (1-27), and 60.9% of patients had nodal metastases. Altogether, 190 had a total thyroidectomy (TT) only, and the median number of nodes resected was 0 (0-10). The percent uptake of radioiodine on the preablation scan was 0.93% in patients who had undergone TT + LVIND and 1.2% in those with TT alone (p = 0.17). The median number of radioactive foci noted within the thyroid bed was two in both groups (p = 0.64). The mean preablation thyroglobulin levels, measured after thyroxine withdrawal or thyrogen stimulation, were 4.0 ng/ml in the TT + LVIND group versus 4.7 ng/ml in the TT group (p = 0.07). The average ablative dose of (131)I was 111.8 mCi in the dissection group and 98.5 mCi in the TT-only group. CONCLUSIONS: There is no evidence that uptake of (131)I is reduced by performance of a central neck dissection in patients with well-differentiated thyroid cancer. Preablation thyroglobulin levels were not altered by level VI lymph node dissection.
PubMed-ID: 22430670
http://dx.doi.org/10.1007/s00268-012-1507-2
Not the Number but the Location of Lymph Nodes Matters for Recurrence Rate and Disease-Free Survival in Patients With Differentiated Thyroid Cancer.
World J Surg, 36(6):1262-7.
de Meer SG, Dauwan M, de KB, Valk GD, Borel Rinkes IH, Vriens MR. 2012.
BACKGROUND: Several Japanese studies have focused on identifying prognostic factors in patients with positive lymph nodes to predict recurrence rate and disease-free survival (DFS). However, different treatment protocol is followed in Japan compared with the European and American approach. This study was designed to investigate whether the number and/or location of lymph nodes predicts prognosis in patients with DTC treated with total thyroidectomy, lymph node dissection, and postoperative radioactive iodine ablation. METHODS: All 402 patients who were treated at the Department of Nuclear Medicine between 1998 and 2010 for DTC were reviewed. Patients were treated with (near) total thyroidectomy, lymph node dissection on indication, and postoperative I-131 ablation. Median follow-up was 49 (range, 10-240) months. Outcome measures were recurrence rate, disease-free survival, and mean time to recurrence. RESULTS: Ninety-seven patients had proven lymph node metastases. Recurrence rate was significantly higher in patients with positive lymph nodes in the lateral compartment vs. patients with lymph node metastasis in the central compartment (60 vs. 30%, p = 0.007). Disease-free survival and mean time to recurrence also were significantly shorter (30 vs. 52 months, p = 0.035 and 7 vs. 44 months, p = 0.004, respectively). The number of lymph nodes and extranodal growth were not significantly associated with the outcome measures used. CONCLUSIONS: The location of positive lymph nodes was significantly correlated with the risk of recurrence and a shorter DFS. Hence, the TNM criteria are useful in subdividing patients based on risk of recurrence and DFS.
PubMed-ID: 22270993
http://dx.doi.org/10.1007/s00268-012-1427-1
Evaluation of Postoperative Radioactive Iodine Scans in Patients Who Underwent Prophylactic Central Lymph Node Dissection.
World J Surg, 36(6):1268-73.
Laird AM, Gauger PG, Miller BS, Doherty GM. 2012.
BACKGROUND: Prophylactic central lymph node dissection (CLND) accompanying total thyroidectomy for papillary thyroid cancer (PTC) remains controversial. Our hypothesis is that CLND may help select patients who benefit from postoperative radioactive iodine (RAI). METHODS: A total of 119 patients who were clinically node-negative underwent total thyroidectomy/bilateral CLND for papillary thyroid cancer (PTC) > 1 cm during 2002-2010. Pathology results, RAI results, and outcomes were compared between node-positive (NP) and node-negative (NN) patients. RESULTS: NP and NN patients were similar in age, gender, tumor size, and MACIS score. Median number of nodes excised was six. The rate of permanent hypocalcemia was 1.7% without permanent recurrent laryngeal nerve injuries. Thirteen of 52 (25%) NN patients and 24 of 67 (36%) NP patients had suspicious nodes by intraoperative inspection. The node assessment negative predictive value was 75%; positive predictive value was 36%. Fifty-six percent (67/118) were NP; 100 patients were treated with RAI. Fourteen of 62 NP patients had abnormal postoperative RAI scans aside from the thyroid remnant versus 4 of 38 NN patients (23 vs. 11%, p = 0.18). Median 1-year stimulated thyroglobulin (Tg) level was 0.0 for both (range 0.0-1.2, NN; 0.0-22.7, NP; p = 0.1). NP patients received higher doses of RAI (150 vs. 30 mCi, p < 0.001). Rate of recurrent or persistent disease was 3.4%. CONCLUSIONS: Few node-negative patients have abnormal RAI scans outside of the thyroid bed. Node-positive patients had greater variability in stimulated 1-year Tg levels after higher doses of RAI. CLND may identify the patients most likely to have persistently elevated stimulated Tg after initial therapy for PTC.
PubMed-ID: 22270997
http://dx.doi.org/10.1007/s00268-012-1431-5
Prognostic Factors for Recurrence of Papillary Thyroid Carcinoma in the Lymph Nodes, Lung, and Bone: Analysis of 5,768 Patients With Average 10-Year Follow-Up.
World J Surg, 36(6):1274-8.
Ito Y, Kudo T, Kobayashi K, Miya A, Ichihara K, Miyauchi A. 2012.
BACKGROUND: Papillary thyroid carcinoma (PTC) frequently recurs to the lymph nodes, which may not be fatal immediately but is a stressor for physicians and patients. Recurrence to the distant organs, although less frequent, is often life-threatening, and the lung and bone are organs to which PTC is likely to recur. In the present study we investigated factors predicting recurrence of PTC to the lymph nodes, lung, and bone in a large number of patients undergoing long-term follow-up. METHODS: A total of 5,768 PTC patients (608 males and 5,159 females) without distant metastasis at diagnosis who underwent initial surgery between 1987 and 2004 in Kuma Hospital were enrolled in this study. The postoperative follow-up ranged from 12 to 280 months, and was 129 months (10.8 years) on average. RESULTS: To date, node, lung, and bone recurrences have been detected in 389 (7%), 118 (2%), and 33 patients (0.6%), respectively, and 57 patients (1%) have died of PTC. We examined the prognostic significance of the tumor size (T), extrathyroid extension (Ex), age 55 years or older (Age), male gender (Gender), clinical node metastasis (N), and extranodal tumor extension (LN-Ex) for each outcome on multivariate analysis. Age, Gender, T > 2 cm, N, and Ex were independent predictors of lymph node recurrence. Age, Ex, T > 2 cm, and N were independent prognostic factors for lung recurrence. Ex, T > 4 cm, and N independently predicted bone recurrence. Of these, N >/= 3 cm had the strongest prognostic value for lymph node, lung, and bone recurrences. In contrast, Age was the strongest predictor for carcinoma death. LN-Ex also had a prognostic value for carcinoma death, although it was not a predictor of carcinoma recurrence. Ex, N >/= 3 cm, and T > 2 cm also had a prognostic impact on carcinoma death. CONCLUSIONS: Large lymph node metastasis showed a strong prognostic impact on carcinoma recurrence not only to the lymph nodes but also to the lung and bone, and carcinoma death. Extrathyroid extension also independently predicted these recurrences and carcinoma death, although hazard ratios were lower than for large node metastasis. Age 55 years or older, in contrast, was the strongest predictor of carcinoma death. Extranodal tumor extension did not independently affect recurrence, but it had prognostic significance for carcinoma death. These findings suggest that recurring PTC lesions of older patients and/or extranodal tumor extensions are difficult to control and very progressive.
PubMed-ID: 22270990
http://dx.doi.org/10.1007/s00268-012-1423-5
Cosmesis and Body Image After Minimally Invasive or Open Thyroid Surgery.
World J Surg, 36(6):1279-85.
Bokor T, Kiffner E, Kotrikova B, Billmann F. 2012.
BACKGROUND: Minimally invasive techniques, such as laparoscopic appendectomy or minimally invasive thyroid surgery, are thought to produce better cosmetic results. However, cosmesis in thyroid surgery was rarely investigated using a standardized approach. The objectives of this study were to evaluate body image and cosmesis in patients who had either minimally invasive (MI) or conventional open (CO) thyroid surgery. METHODS: Two hundred fifty patients of 540 participated (46.3 %): 50 patients (20.0 %) had MI thyroid surgery and 200 (80.0 %) had CO thyroid surgery. The patients filled out a body image questionnaire that investigated body image, cosmesis, and self-confidence. SPSS 19.0 software was used for statistical analysis. RESULTS: Although the mean incision size was significantly shorter in the MI group than in the CO group (2.8 vs. 3.5 cm), the mean scores from the body image questionnaire (body image score, cosmetic score, and self-confidence score) were similar for both groups (p > 0.05). No significant differences in postoperative complications were observed in these groups (p > 0.05). CONCLUSIONS: Studies in the literature that evaluate body image and cosmesis in thyroid surgery using standardized methods are scarce. In our department, the results of a questionnaire showed that the MI approach has no advantage for body image and cosmesis over the CO approach. Further prospective randomized studies using different tools with a larger sample size are needed to investigate the use of MI procedures for thyroid surgery.
PubMed-ID: 22407089
http://dx.doi.org/10.1007/s00268-012-1563-7
Indications for Surgery and Significance of Unrecognized Cancer in Endemic Multinodular Goiter.
World J Surg, 36(6):1286-92.
Lasithiotakis K, Grisbolaki E, Koutsomanolis D, Venianaki M, Petrakis I, Vrachassotakis N, Chrysos E, Zoras O, Chalkiadakis G. 2012.
BACKGROUND: The exclusion of cancer in endemic goiter is often difficult mainly because of the high number of nodules and the as-yet unclear natural history of diagnosed cancer in endemic goiter patients. In a large number of consecutive patients who were to undergo total thyroidectomy for endemic multinodular goiter, we assessed indications for surgery and thyroid cancer outcome. METHODS: All patients who were to undergo total thyroidectomy for diffuse multinodular goiter on histological examination between January 1990 and October 2008 were evaluated. RESULTS: Of the 1,161 patients included in the study, 252 were cases of thyroid cancer (21.7%). Sensitivity of thyroid ultrasound (US) and fine-needle aspiration cytology (FNAC) for cancer detection was 30.3 and 64.1%, respectively. Differentiated thyroid carcinoma accounted for most of the tumors (96%), with 54.8% of them being papillary microcarcinomas, while bilateral-multicentric cancer occurred in 20.3%. In multivariate analysis, younger age (p = 0.06), sonographic findings (p = 0.03), and presence of histological thyroiditis (p = 0.09) were independently associated with the occurrence of tumors with diameter greater than 2 cm. The percentage of transient and permanent postoperative complications were approximately 25 and below 2%, respectively. After a median follow-up time of 78.5 months, overall recurrence rate was 6.7% and disease-specific mortality was 1.2%. CONCLUSION: As US and FNAC did not consistently detect cancer in patients with diffuse multinodular goiter in our endemic area, evidence-based indications for surgery in this group of patients is needed, although radical surgery and favorable tumor histology offer favorable outcomes in commonly diagnosed thyroid cancer after total thyroidectomy for endemic multinodular goiter.
PubMed-ID: 22395348
http://dx.doi.org/10.1007/s00268-012-1554-8
Assessment of Swallowing Function Impairment in Patients With Benign Goiters and Impact of Thyroidectomy: a Case Control Study.
World J Surg, 36(6):1293-9.
Sabaretnam M, Mishra A, Chand G, Agarwal G, Agarwal A, Verma AK, Mishra SK. 2012.
BACKGROUND: Swallowing-related quality of life (QoL) in patients with benign thyroid goiters is not much studied. The aim of this study was to assess swallowing function impairment in patients with benign goiters, compare it to a control population, and also find the impact of thyroidectomy and various factors on the outcome of swallowing function. METHODS: We performed a prospective case-control study from September 2009 to September 2011 which consisted of 124 patients who were to undergo primary thyroid surgery and 100 age- and sex-matched controls. A translated and validated modified swallowing quality-of-life (SWAL-QOL) questionnaire was used to assess patients' perception of dysphagia. Presurgery scores of patients and controls and pre- and postsurgery scores (>6 months after surgery) of patients were compared. RESULTS: The mean age of males and females in the control and patient groups were 37.7 vs. 39.5 years and 37.4 vs. 39.8 years, respectively. Twelve patients (9.7%) complained of dysphasia at presentation. Sixty-three patients (50.8%) underwent total thyroidectomy and 61 (49.2%) had hemithyroidectomy at the time of initial evaluation, 75, 23.4, and 1.6% of patients were euthyroid, hyperthyroid, and hypothyroid, respectively. Presurgery scores of patients in all of the 11 domains of the SWAL-QOL were lower compared to those of controls. Comparing separately with the matched controls, females had significant differences in nine domains (except for sleep and fatigue) of the SWAL-QOL questionnaire but males did not. Postoperatively, both male and female patients showed significant improvement in the scores of all the domains. Female gender, hyperthyroidism, thyroid nodularity, retrosternal extension, procedure, and weight of the resected specimen were the factors associated with significant improvement in various domains. CONCLUSION: Dysphagia seems to be an underestimated problem in patients with benign goiters. Uncomplicated thyroidectomy results in significant improvement in swallowing-related QoL irrespective of patient profile and extent of thyroidectomy.
PubMed-ID: 22422173
http://dx.doi.org/10.1007/s00268-012-1562-8
A Prospective Evaluation of Quick Intraoperative Parathyroid Hormone Assay at the Time of Skin Closure in Predicting Clinically Relevant Hypocalcemia After Thyroidectomy.
World J Surg, 36(6):1300-6.
Lang BH, Yih PC, Ng KK. 2012.
BACKGROUND: Post-thyroidectomy hypocalcemia is a major contributing factor in delayed hospital discharge and dissuading surgeons from ambulatory thyroidectomy. We prospectively evaluated the accuracy and reliability of quick parathyroid hormone level measurement at skin closure (PTH-SC) in predicting clinically relevant hypocalcemia (i.e., patients requiring calcium +/- calcitriol supplements on hospital discharge). METHODS: Of the 117 patients who underwent a total or completion total thyroidectomy and PTH-SC, 17 (14.5 %) had hypocalcemic symptoms or adjusted calcium <1.90 mmol/L requiring calcium and/or calcitriol supplements on discharge. Serum calcium was checked regularly in the perioperative period until stabilization and an additional quick PTH was checked on the following morning (PTH-D1). Univariate and multivariate analyses were performed to evaluate potential preoperative clinicopathologic factors and postoperative day 0 biochemical indicators. Youden's index and the area under the ROC curve (AUC) were used to determine the best cutoff value and predictability of significant variables or criteria, respectively. RESULTS: In the multivariate analysis, low preoperative adjusted calcium (p = 0.041) and low PTH-SC (p = 0.001) were the two independent variables associated with hypocalcemia. PTH-SC (</=1 or >1 pmol/L) had a higher specificity (95.0 %) and AUC (0.887) than serial calcium monitoring or PTH-D1 alone. Although 3/98 of patients with PTH-SC >1 pmol/L required calcium supplements on discharge, they required only the minimum amount to maintain normocalcemia. CONCLUSION: PTH-SC is an accurate and reliable means of predicting clinically relevant hypocalcemia. It would be reasonable to discharge those with PTH-SC >1 pmol/L on the same operative day as the risk of life-threatening hypocalcemia would seem unlikely.
PubMed-ID: 22399155
http://dx.doi.org/10.1007/s00268-012-1561-9
Combining Early Postoperative Parathyroid Hormone and Serum Calcium Levels Allows for an Efficacious Selective Post-Thyroidectomy Supplementation Treatment.
World J Surg, 36(6):1307-13.
Raffaelli M, De CC, Carrozza C, D'Amato G, Zuppi C, Bellantone R, Lombardi CP. 2012.
BACKGROUND: Optimal treatment protocol to prevent symptomatic hypocalcemia following total thyroidectomy is still matter of debate. We prospectively evaluated the efficacy of a selective supplementation protocol based on both early postoperative intact parathyroid hormone (iPTH) and serum calcium levels. METHODS: Two hundred thirty consecutive patients were divided in three different groups of treatment according to iPTH levels 4 h after total thyroidectomy (4 h-iPTH) and serum calcium levels in the first postoperative day (1PO-Ca): group A (4 h-iPTH > 10 pg/ml, 1PO-Ca >/= 8.5 mg/dl), no treatment; group B (4 h-iPTH > 10 pg/ml, 1PO-Ca < 8.5 mg/dl), oral calcium (OC) 3 g per day; and group C (4 h-iPTH </= 10 pg/ml), OC 3 g + calcitriol (VD) 1 mug per day. Development of biochemical and/or symptomatic hypocalcemia was evaluated. RESULTS: Fifty-nine patients (25.6%) had subnormal 4 h-iPTH levels (</=10 pg/ml) (group C). Among patients with normal 4 h-iPTH levels, 25 (10.9%) had subnormal 1PO-Ca (<8.5 mg/dl) (group B). The remaining 146 patients (63.5%) had normal 4 h-iPTH and 1PO-Ca levels (group A). One patient in group A, 2 in group B, and 18 in group C developed biochemical hypocalcemia. Only one patient in group C experienced major symptoms. Treatment was discontinued within 1 month in all the patients in group B. At a mean follow-up of 303 days, five patients in group C were still under supplementation treatment. CONCLUSION: The proposed supplementation protocol seems efficacious in preventing symptomatic hypocalcemia. It could allow a safe and early discharge of most patients, thus avoiding the constraints and the costs of routine supplementation.
PubMed-ID: 22422171
http://dx.doi.org/10.1007/s00268-012-1556-6
Postoperative Hungry Bone Syndrome in Patients With Secondary Hyperparathyroidism of Renal Origin.
World J Surg, 36(6):1314-9.
Goldfarb M, Gondek SS, Lim SM, Farra JC, Nose V, Lew JI. 2012.
BACKGROUND: Hungry bone syndrome (HBS) is a postoperative condition of severe hypocalcemia that can be seen in patients who have undergone parathyroidectomy (PTX) for secondary hyperparathyroidism (2HPT) of renal origin. This study examines HBS in patients after PTX for 2HPT. METHODS: Prospectively collected data was retrospectively reviewed in patients who underwent PTX for 2HPT of renal origin at a single institution. HBS was defined as the need for additional days of hospitalization or readmission for intravenous calcium supplementation due to clinical symptoms of hypocalcemia, including tingling, muscle spasms, and bone pain and/or immediate postoperative low serum calcium </=7.5 mg/dl. RESULTS: Of 79 patients who underwent PTX for 2HPT, 27.8% (n = 22) experienced HBS. Young age (</=45 years, p = 0.02) was the only preoperative variable that predicted HBS. Most patients developed HBS within 18 h after surgery and required a prolonged hospital stay (19/22) compared to those requiring hospital readmission within the first 7 days (3/22). Initial postoperative serum calcium levels within 18 h of surgery were significantly lower in those patients who developed HBS (7.1 vs. 8.3 mg/dl, p = 0.001), and those patients also had a greater absolute decrease in serum calcium (2.8 vs. 3.5 mg/dl, p = 0.04). CONCLUSION: HBS develops in a significant proportion of patients generally within the first 18 h after subtotal PTX for 2HPT. The only identifiable preoperative risk factor for HBS was young age. Additionally, low initial calcium levels and greater absolute decrease in serum calcium may help identify those patients that will develop HBS requiring judicious calcium supplementation.
PubMed-ID: 22399154
http://dx.doi.org/10.1007/s00268-012-1560-x
Preoperative Serum Osteocalcin May Predict Postoperative Elevated Parathyroid Hormone in Patients With Primary Hyperparathyroidism.
World J Surg, 36(6):1320-6.
Rianon N, Alex G, Callender G, Jimenez C, Hu M, Grubbs E, Moreno M, Wathoo C, Petak S, Perrier N. 2012.
BACKGROUND: Persistent postoperative elevation of parathyroid hormone (POePTH) following successful parathyroidectomy for primary hyperparathyroidism (PHPT) is presumed to result from bone remineralization. Predicting which patients may need treatment is difficult. This study investigated whether preoperative serum osteocalcin (OC), a bone turnover marker involved in mineralization, can predict POePTH. METHODS: A total of 198 patients (155 women and 43 men) with parathyroidectomy from November 2007 to October 2009 in MD Anderson Cancer Center, Houston, TX, USA, were included in our analysis. Separate multivariate regression models determined associations between preoperative OC and POePTH at 6 and 12 months postoperatively. Regression models were adjusted for demographics (age, gender, race, height, weight, BMI), preoperative BMD and bisphosphonate use, adenoma weight, serum levels of PTH, calcium, vitamin D, creatinine, and phosphate. Patients with baseline GFR <60 ml/min/1.73 m(2) and postoperative serum calcium >10.14 mg/dl at 6 and 12 months were excluded. RESULTS: Patients' mean age (+/-SD) was 60 (+/-14) years. POePTH (>80 pg/ml) occurred in 13 and 12% patients at 6 and 12 months, respectively. Preoperative serum creatinine and bisphosphonate use were positively associated with POePTH (p < 0.05) both at 6 and 12 months. Preoperative OC was predictive of POePTH (p < 0.05) at 6 months (beta 0.35; 95% confidence interval (CI), 0.11-0.58) and at 12 months (beta 0.79; 95% CI, 0.27-1.31). CONCLUSIONS: Preoperative OC may help to predict risk of POePTH in patients with PHPT. Research with longer follow-up in patients with no known baseline chronic kidney disease stratified by high versus normal preoperative serum creatinine is recommended.
PubMed-ID: 22278606
http://dx.doi.org/10.1007/s00268-012-1432-4
Thoracoscopic Removal of Mediastinal Parathyroid Lesions: Selection of Surgical Approach and Pitfalls of Preoperative and Intraoperative Localization.
World J Surg, 36(6):1327-34.
Iihara M, Suzuki R, Kawamata A, Horiuchi K, Okamoto T. 2012.
BACKGROUND: Thoracoscopic surgery has replaced conventional sternotomy or thoracotomy for resection of mediastinal parathyroid lesions. We review our experience with this type of surgery with reference to selection of the appropriate approach and the pitfalls of lesion localization before and during surgery. METHODS: During a 14-year period, we treated 14 patients with hyperparathyroidism, in whom a mediastinal lesion had been localized preoperatively by sestamibi scan. Primary hyperparathyroidism was present in 12 patients (single adenoma in 11, associated with MEN 1 in one) and secondary hyperparathyroidism in 2. Thoracoscopic procedures were performed by the three-port method. RESULTS: The thoracoscopic procedure was successful in eight patients who were shown preoperatively to have a deep-seated (5 anterior, 3 middle) mediastinal lesions. Intraoperative visual confirmation of parathyroid adenoma was difficult only in a 19-year-old patient with a tumor embedded in the thymus, necessitating partial thymectomy. One of the eight mediastinal lesions resected thoracoscopically was a sestamibi-positive thymoma. Secondary hyperparathyroidism recurred 4 years after thoracoscopic mediastinal parathyroidectomy in one patient, necessitating additional thoracoscopic removal of this supernumerary lesion. However, seven patients with mediastinal parathyroid lesions localized at the aortic arch or upper region were treated successfully via a cervical approach. None of the patients suffered any surgical complications. CONCLUSIONS: Thoracoscopic surgery is safe and feasible for resection of deep mediastinal parathyroid lesions. Such lesions localized preoperatively at the aortic arch or upper region can be treated via a cervical approach. Preoperative sestamibi scan can sometimes give a false-positive result in cases of concurrent thymoma.
PubMed-ID: 22205108
http://dx.doi.org/10.1007/s00268-011-1404-0
Parathyroid Four-Dimensional Computed Tomography: Evaluation of Radiation Dose Exposure During Preoperative Localization of Parathyroid Tumors in Primary Hyperparathyroidism.
World J Surg, 36(6):1335-9.
Mahajan A, Starker LF, Ghita M, Udelsman R, Brink JA, Carling T. 2012.
BACKGROUND: Parathyroid four-dimensional computed tomography (4DCT) provides greater sensitivity than sestamibi with single photon emission CT (SPECT, or SeS) for preoperative localization of parathyroid tumors in patients with primary hyperparathyroidism (PHPT). The radiation dose imparted to the patient during preoperative parathyroid imaging, however, has not been analyzed. METHODS: Patients with biochemically unequivocal PHPT referred for minimally invasive parathyroidectomy underwent 4DCT or SeS. 4DCT was performed using a 64 detector row CT scanner, and SeS used a standardized protocol of 20 mCi of technetium-99m followed by planar and SPECT imaging. The CT radiation dose was estimated using the Imaging Performance Assessment of CT Scanners (ImPACT) calculator, and the SeS dose was estimated using the US Nuclear Regulatory Commission Regulation (NUREG) method. RESULTS: The calculated effective doses of 4DCT and SeS were 10.4 and 7.8 mSv, respectively, in contrast to an estimated annual background radiation exposure of approximately 3 mSv. The dose to the thyroid with 4DCT, however, was about 57 times higher (92.0 vs. 1.6 mGy) than that with SeS. Based on age- and sex-dependent risk factors, the calculated risk of 4DCT-related thyroid cancer developing in a 20 year old woman was 1,040/million (i.e., about 0.1%). CONCLUSIONS: 4DCT, a superior preoperative imaging modality for locating parathyroid tumors, imparts a significantly higher thyroid radiation dose than SeS. Given the enhanced risk of thyroid cancer in individuals with radiation exposure at a young age, 4DCT should be used judiciously in young PHPT patients.
PubMed-ID: 22146947
http://dx.doi.org/10.1007/s00268-011-1365-3
Randomized Controlled Trial of Visualization Versus Neuromonitoring of the External Branch of the Superior Laryngeal Nerve During Thyroidectomy.
World J Surg, 36(6):1340-7.
Barczynski M, Konturek A, Stopa M, Honowska A, Nowak W. 2012.
BACKGROUND: Injury to the external branch of the superior laryngeal nerve (EBSLN) during thyroidectomy results in a lowered fundamental frequency of the voice and deteriorated voice performance in producing high-frequency sounds. It remains unclear if the use of intraoperative nerve monitoring (IONM) can improve the clinical outcome of thyroidectomy in terms of preserved individual voice performance. This study was designed to test that hypothesis. METHODS: A total of 210 consenting female patients planned for total thyroidectomy were randomly assigned to two groups equal in size (n = 105): visual inspection of the EBSLN and RLN vs. this plus additional EBSLN and RLN monitoring. The primary outcome was the identification rate of the EBSLN. The secondary outcomes included: anatomical variability of the EBSLN according to the Cernea classification and changes in postoperative voice performance. Voice assessment included pre- and postoperative videostrobolaryngoscopy and an analysis of maximum phonation time (MPT), voice level (VL), fundamental frequency (Fo), and voice quality rating on the GRBAS scale. RESULTS: The following differences were found for operations without vs. with IONM: identification rate of the EBSLN was 34.3 % vs. 83.8 % (p < 0.001), whereas a 10 % or higher decrease in phonation parameters was found in 10 % vs. 2 % patients for MPT (p = 0.018), 13 % vs. 2 % for VL (p = 0.003), and 9 % vs. 1 % for Fo (p = 0.03), a change in the GRBAS scale > 4 points in 7 % vs. 1 % (p = 0.03), and temporary RLN injury was found in 2 % vs. 1 % (p = 0.56), respectively. CONCLUSIONS: The use of IONM significantly improved the identification rate of the EBSLN during thyroidectomy, as well as reduced the risk of early phonation changes after thyroidectomy.
PubMed-ID: 22402975
http://dx.doi.org/10.1007/s00268-012-1547-7
Intraoperative Neuromonitoring Does Not Reduce the Incidence of Recurrent Laryngeal Nerve Palsy in Thyroid Reoperations: Results of a Retrospective Comparative Analysis.
World J Surg, 36(6):1348-53.
Alesina PF, Rolfs T, Hommeltenberg S, Hinrichs J, Meier B, Mohmand W, Hofmeister S, Walz MK. 2012.
PURPOSE: Recurrent laryngeal nerve (RLN) palsy is the major concern of reoperative thyroid surgery, and the introduction of neuromonitoring could reduce the rate of this complication. The present study is a retrospective analysis of the experience with completion thyroidectomy with and without neuromonitoring in a referral center. METHODS: Between October 1999 and April 2011, 246 patients [37 men, 209 women; mean age, 55 +/- 12.5 (range, 25-80) years] underwent 250 reoperations for recurrent goiter (n = 203), hyperthyroidism (n = 26), or recurrent thyroid cancer (n = 17). The mean interval between the initial and the reoperative procedure was 17.5 years. According to the availability of the neuromonitoring system and to the surgeon preference, 91 operations were performed with neuromonitoring (NM-group), whereas 159 were performed with direct nerve visualization (NV-group) alone. Patients' characteristics, perioperative data, and postoperative complications were collected in a prospectively maintained database. RESULTS: In the NM-group, 51 unilateral and 40 bilateral resections were performed. The NV-group included 122 unilateral and 37 bilateral procedures. The number of nerves at risk after previous surgery was 128 (NM-group) and 161 (NV-group), respectively. We registered eight RLN palsy in the NM-group (6.2 %) and four in the NV-group (2.5 %; p = 0.1). CONCLUSIONS: The routine use of intraoperative neuromonitoring seems not to reduce the incidence of RLN during redo thyroid surgery, at least in the setting of a tertiary referral center.
PubMed-ID: 22411090
http://dx.doi.org/10.1007/s00268-012-1548-6
Prospective Electromyographic Evaluation of Functional Postthyroidectomy Voice and Swallowing Symptoms.
World J Surg, 36(6):1354-60.
Lombardi CP, D'Alatri L, Marchese MR, Maccora D, Monaco ML, De CC, Raffaelli M. 2012.
BACKGROUND: Voice and swallowing symptoms following thyroidectomy in the absence of any demonstration of laryngeal nerves injury are usually considered a functional outcome of uncomplicated operations, mainly related to scar formation and emotional reaction. They could be related to unapparent laryngeal nerve or cricothyroid (CT) muscle injuries detectable only by laryngeal electromyography (LEMG). We correlated such symptoms with LEMG patterns. METHODS: A total of 33 consenting patients undergoing total thyroidectomy (TT) were enrolled. Video-strobolaryngoscopy (VSL), acoustic voice analysis (AVA), and maximum phonation time (MPT) were performed preoperatively and 3 months postoperatively. Subjective evaluation of voice (Voice Impairment Score, or VIS) and swallowing (Swallowing Impairment Score, or SIS) were obtained preoperatively and 1 and 3 months postoperatively. At 1 month postoperatively LEMG was performed examining thyroarytenoid (TA) and CT muscles to evaluate the inferior laryngeal nerve (ILN) and the external branch of the superior laryngeal nerve (EBSLN), respectively. RESULTS: One patient experienced transient vocal cord palsy and was excluded. The remaining 32 patients completed the postoperative evaluation. No significant difference was found between preoperative and postoperative AVA and MPT parameters. Mean VIS was significantly worse than preoperatively 1 and 3 months after TT. No significant difference was found between preoperative and postoperative SIS. LEMG evaluation of TA muscle showed decreased voluntary activity and spontaneous fibrillation potentials in one patient. LEMG of the CT muscle did not reveal any sign of EBSLN injury. CONCLUSIONS: Patients frequently complain of subjective symptoms early after TT. LEMG demonstrated the absence of subclinical laryngeal nerve injury in all but one patient, confirming their functional nature.
PubMed-ID: 22382763
http://dx.doi.org/10.1007/s00268-012-1481-8
Heat Production, Nerve Function, and Morphology Following Nerve Close Dissection With Surgical Instruments.
World J Surg, 36(6):1361-7.
Carlander J, Koch C, Brudin L, Nordborg C, Gimm O, Johansson K. 2012.
BACKGROUND: The aim of the present study was to compare an ultrasonically activated instrument (US), monopolar electrosurgery, and bipolar electrosurgery (ES) with respect to heat production, nerve function, and nerve morphology following in vivo application. MATERIALS AND METHODS: The biceps femoris muscle of anesthetized rats was cut in a standardized manner longitudinally 1 mm adjacent to the sciatic nerve using US shears, a monopolar ES knife, or a bipolar ES scissors. Activation time and temperature were recorded continuously within 1-4 mm of the activation site ipsilateral and contralateral to the nerve with two thermoelectric microsensors. Temperature rise and time delay of reaching the temperature maximum, as an expression of heat spread within tissue, maximum temperature, and thermal dose (equivalent time of exposure at 43 degrees C) were measured and calculated. A total of 49 functional experiments were conducted. The electromyographic (EMG) potential was recorded distally. Nerve dysfunction was defined as more than 10% loss of the evoked EMG amplitude. Forty-eight nerves were coded and submitted to blind histopathological examination, and morphological damage was graded on a 4-grade scale. RESULTS: The maximum temperature elevation and the thermal dose were significantly higher for the bipolar ES compared with the US instrument (p = 0.024, p = 0.049), and with much less variation of results for the US instrument. The monopolar ES maximum temperature and thermal dose were lower, but a very large variation occurred, probably as a result of more random electrical spread to the ground electrode and muscle motion artifacts. Functional loss was least common in the US group-without being significant-compared to bipolar and monopolar ES. Moderate and severe morphological damage was significantly less common in the US group than in the monopolar ES group (p = 0.041). We found no statistically significant correlation between the highest temperatures and the degree of morphological damage or functional loss. CONCLUSIONS: The temperature elevation depends strongly on the distance to the activated instrument. The bipolar ES scissors generates a higher maximum temperature and thermal dose with a greater variation in than the US. Functional loss and severe morphological damage were uncommon in all groups.
PubMed-ID: 22366981
http://dx.doi.org/10.1007/s00268-012-1471-x
Preoperative Localizing Studies for Initial Parathyroidectomy in MEN1 Syndrome: Is There Any Benefit?
World J Surg, 36(6):1368-74.
Nilubol N, Weinstein L, Simonds WF, Jensen RT, Phan GQ, Hughes MS, Libutti SK, Marx S, Kebebew E. 2012.
BACKGROUND: The objective of the present study was to evaluate the utility of preoperative localizing studies in patients with MEN1 undergoing initial bilateral neck exploration (BNE) and parathyroidectomy for pHPT. METHODS: We performed a retrospective analysis of patients diagnosed with MEN1 who underwent initial parathyroidectomy between December 1993 and December 2010. Results of preoperative localizing studies were compared with intraoperative findings and outcome. RESULTS: Sixty patients with MEN1 (32 females and 28 males) underwent initial subtotal parathyroidectomy. The median age at the time of surgery was 33 years (range: 13-78 years). Fifty-three patients had one or more positive localizing study results. Neck ultrasonography, sestamibi scan, parathyroid protocol computed tomography scan, and neck and mediastinum magnetic resonance imaging were performed in 93, 91, 32, and 19% of patients, respectively. Fifty-three patients (88%) had cervical thymectomy. Twenty patients had 24 ectopic parathyroid glands; 18 glands were in the thymus (75%). Preoperative localizing studies identified 9 of 24 ectopic parathyroid glands (38%), including 4 ectopic glands outside the thymus in 4 patients (7%); 3 were detected by ultrasonography. There were no supernumerary glands identified on preoperative localizing studies. CONCLUSIONS: In patients with MEN1, preoperative localizing studies identified a subset of ectopic glands (38%). Preoperative localizing studies may alter the operative approach in 7% of patients. Ultrasonography can detect most ectopic parathyroid glands outside thymus. This suggests that routine preoperative localizing studies to identify ectopic and supernumerary enlarged parathyroid glands is not useful in the majority of patients with MEN1 undergoing bilateral neck exploration and subtotal parathyroidectomy with cervical thymectomy.
PubMed-ID: 22350475
http://dx.doi.org/10.1007/s00268-012-1451-1
Preoperative Assessment of the Pancreas in Multiple Endocrine Neoplasia Type 1.
World J Surg, 36(6):1375-81.
Lewis MA, Thompson GB, Young WF, Jr. 2012.
BACKGROUND: Many serologic and radiographic modalities are used for monitoring multiple endocrine neoplasia type 1 (MEN 1) patients for pancreaticoduodenal neuroendocrine tumors (PNETs). We compared serum markers and imaging studies obtained preoperatively with the gross pathology and immunohistochemical findings and correlated preoperative testing with postoperative outcome. METHODS: From 2000 to 2008, 52 MEN 1 patients [32 (62%) female; median age = 43 years, range 19-74 years] underwent 56 pancreatic operations [49 (88%) distal pancreatectomies] for suspected PNETs. Preoperative serum markers [human pancreatic polypeptide (HPP), gastrin, and glucagon] and imaging [CT, (111)In pentetreotide scintigraphy, and endoscopic ultrasound (EUS)] were compared to the pathologic findings. Postoperative serum markers and survival were followed. RESULTS: Human pancreatic polypeptide had the highest agreement between an elevated serum level and positive tumor immunostaining (83% vs. 50% agreement for gastrin vs. 67% agreement for glucagon). Preoperative CT had 81% sensitivity and positive predictive value (PPV) of 97% for PNETs. (111)In pentetreotide scintigraphy had 84% sensitivity and PPV of 96%. Preoperative endoscopic ultrasonography (EUS) had 100% sensitivity and PPV, with close correlation (r (s) = 0.93) between the largest lesion seen on EUS and pathology. Median follow-up was 4.3 years (range = 0.1-10.9 years). Overall survival was 89% at 5-year follow-up. CONCLUSIONS: Our study substantiates EUS as providing the highest preoperative sensitivity and PPV in assessing the presence of PNETs in MEN 1 patients. CT and octreotide scintigraphy can yield both false-positive and false-negative results. HPP, gastrin, and glucagon were the most commonly measured tumor markers in our series but did not always correlate with immunostaining. With an aggressive surgical approach, satisfactory rates of biochemical improvement and long-term survival were observed.
PubMed-ID: 22382771
http://dx.doi.org/10.1007/s00268-012-1539-7
Ectopic Hormone-Secreting Pheochromocytoma: a Francophone Observational Study.
World J Surg, 36(6):1382-8.
Kirkby-Bott J, Brunaud L, Mathonet M, Hamoir E, Kraimps JL, Tresallet C, Amar L, Rault A, Henry JF, Carnaille B. 2012.
BACKGROUND: Ectopic hormone-secreting pheochromocytomas are rare; only case reports exist in the literature. This condition has been linked with increased malignancy, familial syndromes, and ACTH secretion. We wanted to test these hypotheses and shed light on the nature of ectopic hormone-secreting pheochromocytomas. METHODS: This is a multicenter (francophone) observational study. Inclusion was based upon abnormal preoperative hormone tests in patients with pheochromocytoma that normalized after removal of the tumor. Where possible, immunohistochemistry was performed to confirm that ectopic secretion came from the tumor. RESULTS: Sixteen cases were found: nine female and seven male patients. Median age was 50.5 (range 31-89) years. Most presented with hypertension, diabetes, or cushingoid features. Ten patients had specific symptoms from the ectopic hormone secretion. Two had a familial syndrome. Of eight patients with excess cortisol secretion, three died as a result of the tumor resection: two had pheochromocytomas >15 cm and their associated cortisol hypersecretion complicated their postoperative course. The other died from a torn subhepatic vein. The 13 survivors did not develop any evidence of malignancy during follow-up (median 50 months). Symptoms from the ectopic secretion resolved after removal of the tumor. Immunohistochemistry was performed and was positive in eight tumors: five ACTH, three calcitonins, and one VIP. CONCLUSIONS: Most pheochromocytomas with ectopic secretion are neither malignant nor familial. Most ectopic hormone-secreting pheochromocytoma cause hypercortisolemia. Patients with a pheochromocytoma should be worked up for ectopic hormones, because removal of the pheochromocytoma resolves those symptoms. Associated cortisol secretion needs careful attention.
PubMed-ID: 22362045
http://dx.doi.org/10.1007/s00268-012-1488-1
Prevalence of Germline Mutations in Patients With Pheochromocytoma or Abdominal Paraganglioma and Sporadic Presentation: a Population-Based Study in Western Sweden.
World J Surg, 36(6):1389-94.
Muth A, Abel F, Jansson S, Nilsson O, Ahlman H, Wangberg B. 2012.
BACKGROUND: Germline mutations in the susceptibility genes RET, SDHB, SDHD, and VHL have been reported in 7.5-24% of patients with pheochromocytoma (Pheo) or paraganglioma (PGL) and sporadic presentation. The purpose of the present study was to establish population-based data on the frequency of germline mutations in patients with apparently sporadic Pheo or abdominal PGL in Western Sweden. METHODS: From the Swedish National Cancer Registry, all patients with Pheo or PGL in Western Sweden (population 1.72 million) registered between 1958 and 2009 were identified (n = 256). Patients were characterized using register data, hospital records, and clinical interviews. All living patients with Pheo or abdominal PGL and sporadic presentation (n = 81) were invited to genetic screening; 71 patients accepted. Germline mutations were investigated by using direct sequencing for point mutations in RET, SDHB, SDHD, and VHL, and multiplex ligation-dependent probe amplification for gross deletions in SDHB, SDHC, SDHD, and VHL. Plasma or urinary metanephrines and/or urinary catecholamines were used for biochemical follow-up. RESULTS: The prevalence of germline mutations was 5.6%. Mutations were only seen in RET (n = 1) and SDHB (n = 3). Notably, in the patients with SDHB mutations, no malignant phenotype was observed during a mean follow-up of 23.3 years. CONCLUSIONS: The frequency of germline mutations in patients with apparently sporadic Pheo and abdominal PGL in Western Sweden was lower than in previous studies. Variations in reported frequencies of germline mutations in patients with clinically sporadic Pheo/PGL may reflect geographical differences or patient selection.
PubMed-ID: 22270996
http://dx.doi.org/10.1007/s00268-012-1430-6
Single-Incision Transperitoneal Laparoscopic Left Adrenalectomy.
World J Surg, 36(6):1395-9.
Vidal O, Astudillo E, Valentini M, Ginesta C, Garcia-Valdecasas JC, Fernandez-Cruz L. 2012.
BACKGROUND: Laparoscopic adrenalectomy via three or four trocars is a well-established procedure. This report describes the initial experience with single-incision laparoscopic surgery (SILS) using the transperitoneal approach for left adrenalectomy. METHODS: Between April 2010 and August 2011, all consecutive patients with adrenal masses, including Conn's syndrome, Cushing's adenoma, and nonfunctional adrenal tumors, who agreed to undergo SILS adrenalectomy were included in a prospective study. The left 2.5-cm subcostal incision was the sole point of entry. Data of patients who underwent SILS adrenalectomy were compared with those from an uncontrolled group of patients who underwent conventional laparoscopic adrenalectomy during the same study period. RESULTS: There were 20 patients in each study group (20 men, 20 women; mean age [SD] = 50 [6.5] years). SILS was successfully performed and none of the patients required conversion to an open procedure. In one case of SILS procedure, an additional lateral 5-mm port was needed for retraction of the kidney. The mean (SD) duration of the operation was 95 (20) min in the SILS group and 80 (8) min in the conventional laparoscopic adrenalectomy group (p = 0.052). There were no intraoperative or postoperative complications. There were no differences between the two study groups with respect to postoperative pain, number of patients who resumed oral intake within the first 24 h, final pathologic diagnosis, and length of hospital stay. CONCLUSION: SILS left adrenalectomy is a technically feasible and safe procedure in carefully selected patients. The definitive clinical, aesthetic and functional advantages of this technique require further analysis.
PubMed-ID: 22392358
http://dx.doi.org/10.1007/s00268-012-1555-7
Adrenalectomy Improves Outcomes of Selected Patients With Metastatic Carcinoma.
World J Surg, 36(6):1400-5.
Vazquez BJ, Richards ML, Lohse CM, Thompson GB, Farley DR, Grant CS, Huebner M, Moreno J. 2012.
BACKGROUND: Indications and survival benefit for adrenalectomy (ADX) in the setting of metastasis are not clearly defined. We aimed to determine which patients with primary malignancies may benefit from ADX performed for metastasis. Mayo Clinic institutional outcomes in patients with metastatic disease to the adrenal(s) treated by adrenalectomy were compared to stage-matched historical controls from the Surveillance Epidemiology and End Results (SEER) database. METHODS: A retrospective review (1992-2010) was conducted to identify patients treated with ADX for metastatic cancer at Mayo Clinic, Rochester. Associations of clinical, surgical, and pathologic features with overall survival (OS) were evaluated using Cox proportional regression models. OS for those treated with ADX was compared with that for SEER database stage-matched patients who underwent primary resection without resection of distant disease using log-rank tests. RESULTS: A total of 166 patients underwent ADX for metastatic primaries involving the kidney 60, lung 24, sarcoma 19, colon 15, pancreas 13, and other-35. Patients with sarcoma and kidney, lung, and pancreatic tumors who underwent ADX had better OS at 1, 2, and 3 years than did the SEER-matched controls. Respectively, the rates were for sarcoma (100, 93, 86% vs. 57, 36, 30%), kidney (86, 80, 72% vs. 55, 37, 27%), lung (91, 69, 52% vs. 52, 34, 25%), and pancreas (79, 56, 45% vs. 33, 20, 12%). Univariate analysis identified primary diagnosis <2 years before ADX, other distant site, pancreatic primary, palliative operation, and persistent disease as risk factors for death. CONCLUSIONS: An aggressive surgical approach results in improved OS in patients with metastatic disease arising from soft tissues, kidney, lung, and pancreas. Other tumors may benefit, but larger study cohorts are needed for a meaningful comparison.
PubMed-ID: 22411083
http://dx.doi.org/10.1007/s00268-012-1506-3
Preoperative 18F-FDG Uptake Is Strongly Correlated With Malignancy, Weiss Score, and Molecular Markers of Aggressiveness in Adrenal Cortical Tumors.
World J Surg, 36(6):1406-10.
Gust L, Taieb D, Beliard A, Barlier A, Morange I, de MC, Henry JF, Sebag F. 2012.
BACKGROUND: Adrenal incidentaloma are frequent in the general population. It can be difficult to diagnose adrenocortical carcinomas among them, even with the progress of imaging techniques. We studied the results of PET-FDG in the diagnosis of such tumours. METHODS: We studied patients referred to the Department of Endocrine Surgery at La Timone Hospital, Marseilles, France, between June 2006 and October 2010 for adrenal tumours. All patients underwent a complete work-up (biological tests and imagery), completed with PET-FDG. We compared the results of PET-FDG and molecular analysis with Weiss score and clinical follow-up. We calculated correlations with the Pearson test. RESULTS: A total of 51 patients were studied. We found that PET-FDG had a sensitivity of 95% and specificity of 97% for the diagnosis of adrenocortical carcinoma. The correlation between PET-FDG and Weiss score was 77% (P </= 0.0001). Molecular analyses were correlated as well with Weiss score and malignancy (P < 0.05). CONCLUSIONS: The nature of atypical adrenal masses can be difficult to define during preoperative investigations. For undetermined tumours smaller than 6 cm, characterization with PET-FDG can be one more diagnostic argument pointing to malignancy. It could potentially change the therapeutic strategy and surgical management. In our experience, molecular analyses are available after surgery and have less impact on the therapeutic strategy than PET-FDG. Preoperative PET-FDG can be an asset in the management of adrenal incidentaloma and adrenocortical carcinoma.
PubMed-ID: 22131094
http://dx.doi.org/10.1007/s00268-011-1374-2
Prognostic Relevance of Survivin in Pancreatic Endocrine Tumors.
World J Surg, 36(6):1411-8.
Ekeblad S, Lejonklou MH, Stalberg P, Skogseid B. 2012.
BACKGROUND: Better prognostic markers are needed for pancreatic endocrine tumors. Survivin is an apoptosis inhibitor that is suggested to have a negative prognostic impact in several tumor types. Contradictory data exist, especially regarding the significance of a nuclear versus cytoplasmic location of survivin. The prognostic relevance of nuclear and cytoplasmic survivin expression in pancreatic endocrine tumors-controlled for the tumor Ki-67 index, World Health Organization classification, and TNM stage-was investigated. METHODS: A total of 111 patients treated at a tertiary referral center were retrospectively evaluated. Clinical data were gathered from medical records. Immunohistochemistry for survivin and Ki-67 was performed on paraffin-embedded tissue. Univariate and multivariate Cox analyses were performed. RESULTS: Patients with tumors that had <5% survivin-positive nuclei had a mean survival of 225 months [95% confidence interval (CI) 168-281]. The corresponding figure for patients with 5 to 50% survivin-positive tumor cell nuclei was 101 months [95% CI 61-140; hazard ratio (HR) 2.4; P < 0.01) and with >50% survivin-positive nuclei 47 months (95% CI 24-71; HR 4.9; P < 0.001). Nuclear survivin expression in >50% of the tumor cells was an independent marker of a poor prognosis (HR 5.7; P < 0.01). Cytoplasmic survivin was not a significant prognostic factor in the multivariate analysis (HR 0.94; P = 0.90). CONCLUSIONS: High expression of nuclear survivin is a significant marker of a poor prognosis in patients with a pancreatic endocrine tumor.
PubMed-ID: 22089920
http://dx.doi.org/10.1007/s00268-011-1345-7
Long-Term Results of Surgery for Small Intestinal Neuroendocrine Tumors at a Tertiary Referral Center.
World J Surg, 36(6):1419-31.
Norlen O, Stalberg P, Oberg K, Eriksson J, Hedberg J, Hessman O, Janson ET, Hellman P, Akerstrom G. 2012.
BACKGROUND: Small intestinal neuroendocrine tumors (SI-NETs) are uncommon, with an annual incidence of about 1 per 100,000 individuals. The primary tumor (PT) is generally small, but nevertheless the majority of patients have mesenteric lymph node metastases and liver metastases at diagnosis. Our aim was to identify prognostic factors for survival and to evaluate outcome after surgery in SI-NET patients. MATERIAL AND METHODS: We included 603 consecutive patients (325 men; age at diagnosis 63 +/- 11 years [mean +/- SD]) with histopathologically verified SI-NET, who were diagnosed between 1985 and 2010. Hospital charts were reviewed and were scrutinized for carcinoid heart disease (CHD), flush and/or diarrhea, proliferation by Ki-67 index, mesenteric lymph node metastases (m.lgllm), distant abdominal lymph node metastases (da.lgllm), liver tumor load (LTL), extra-abdominal metastases (EAM), locoregional resective surgery, as well as debulking of LTL, and adverse events after surgery. RESULTS: Median overall survival (OS) was 8.4 years; 5-year OS was 67%, and 5-year relative survival was 74%. Independent prognostic factors by univariate and multivariate analysis were age at diagnosis, CHD, m.lgllm, da.lgllm, LTL, EAM, peritoneal carcinomatosis (PC), and proliferation. Locoregional resective surgery was associated with increased survival on crude and multivariate analysis. The 30-day mortality in our institution after initial locoregional resective surgery was 0.5% (1/205). CONCLUSIONS: For the first time, m.lgllm and da.lgllm, LTL, PC, and EAM are demonstrated to be independent prognostic factors by multivariate analysis. Locoregional removal of the PT/m.lgllm. was a positive prognostic factor by crude and adjusted analysis and may influence survival.
PubMed-ID: 21984144
http://dx.doi.org/10.1007/s00268-011-1296-z