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1.  A Large Nonmetastatic Anaplastic Thyroid Cancer with Complete Thyroidal Confinement 
Case Reports in Medicine  2011;2011:583978.
Anaplastic thyroid cancer (ATC) is rare but extremely aggressive, which accounts for about 2% of all thyroid cancers yet nearly 50% of thyroid-cancer-associated deaths in the United States. The median survival time from diagnosis is 5 months, with a 1-year survival rate of only 20%. We report here a case of ATC in a 56-year-old man who survived a large ATC. Preoperative fine-needle aspiration biopsy study to a large right thyroid mass suggested ATC. Total thyroidectomy with radical lateral neck and central neck dissection removed a well-circumscribed 9.5 cm tumor without extrathyroidal extension or lymphovascular invasion. All 73 lymph nodes removed were negative for metastasis. The tumor consisted of highly pleomorphic, undifferentiated cells with large zones of necrosis and loss of thyroid transcription factor-1 and thyroglobulin expression. A focal well-differentiated component and PAX8 expression confirmed its thyroid follicular cell origin. Nine months after postsurgical adjuvant concurrent radiation therapy and chemotherapy, the patient remained well without clinical, biochemical, and radiographical evidence for cancer recurrence. This is an unusual case of ATC in that it is one of the largest ATC tumors reported to display mild pathologic behavior and relatively long-term patient survival.
doi:10.1155/2011/583978
PMCID: PMC3170804  PMID: 21912554
2.  Aggressive Multimodal Approach for Anaplastic Thyroid Cancer and Long-Term Survival 
Anaplastic thyroid cancer (ATC) comprises 1-2% of all thyroid cancers and is one of the most aggressive cancers with a median survival rate of around four months. The average 5-year survival rate has been reported to be around 3.6%. In this paper, we have discussed management and prognostic variables of a patient with ATC who has survived for more than 5 years. A 59-year-old female was referred to our facility for an elective thyroid and parathyroidectomy for concerns of thyroid papillary cancer and hyperparathyroidism. At the time of surgery, the tumor mass had invaded the muscular layer of esophagus; radicle thyroidectomy parathyroidectomy along with removal of muscle layer of esophagus was performed, and diagnosis of ATC was made. The patient was treated with chemoradiation with a good treatment response and no recurrence of tumor for two and a half years until PET/CT followed by wedge biopsy of lung confirmed ATC recurrence. The patient was treated with another course of radiation treatment with a good treatment response. Since then, the patient has been following in our outpatient oncology clinic and has no evidence of tumor recurrence. Aggressive multimodal approach of combining radicle surgery with chemoradiation treatment in select patients of ATC with no distant metastasis helps improve prognosis.
doi:10.1155/2013/783862
PMCID: PMC3600220  PMID: 23533874
3.  Indications for the Gasless Transaxillary Robotic Approach to Thyroid Surgery: Experience of Forty-Seven Procedures at the American Hospital of Paris 
European Thyroid Journal  2013;2(2):102-109.
Background
Thyroid surgery is in a state of evolution from traditional open approaches to novel robotic techniques. The gasless transaxillary approach to thyroid surgery is effective in the management of thyroid cancer, and complications after robotic thyroidectomy are no higher than experienced after open or endoscopic techniques. The transaxillary robotic approach also avoids an anterior neck scar. This paper presents what the authors believe to be the largest cohort of patients reported in Europe undergoing gasless transaxillary robotic thyroid surgery, with the aim of defining the indications for this procedure.
Methods
Forty-six patients underwent robotic thyroid surgery via the transaxillary approach and were enrolled in this study between March 2010 and September 2012. All patients were operated on by one surgeon at one clinical center. Reviewed data included patient characteristics, pathological characteristics, extent of surgery and postoperative complications. The mean follow-up time was 7.29 months.
Results
Forty-six patients underwent 47 procedures, the average age of the patients was 43 years and the male to female ratio was 1:22. Undertaken were 30 lobectomies, 3 subtotal thyroidectomies, 13 total thyroidectomies and 1 totalization. One case was converted to an open procedure. The ratio of malignant to benign disease was 1:6.67 (6:40 cases) and analysis of the surgical specimens showed 6 follicular lesions, 24 follicular adenomas, 3 colloid lesions, 1 case of thyroiditis/lymphatic lesion, 3 adenomatoid lesions, 3 oncocytic adenomas, 3 papillary cancers and 3 microcapillary cancers. The overall average size of an individual specimen removed was 45.40 ± 28.95 cm3 (range 5-160, n = 47) and the average largest diameter of the lesion removed was 3.72 ± 0.95 cm (range 1.4-6.0, n = 47). Postoperatively, there were 5 recurrent laryngeal nerve injuries (4 transient), 2 transient brachial plexopathies, 1 case of postoperative dysphagia and 1 of collection of blood at the site of surgery. There were no cases of disease recurrence at follow-up.
Conclusions
The gasless robotic transaxillary approach to thyroid surgery has been predicted to become a standard technique. It has been shown to be efficacious in the management of thyroid cancer with lateral neck metastases; however, more data relating to oncological safety in long-term follow-up is required. This intervention is also appropriate for benign thyroid disease including Graves' disease. To achieve consistently successful results, careful patient selection is fundamental in terms of patient characteristics and the anatomical aspects of the lesion. This is especially important with a geographical expansion to include North America and Europe. The excellent cosmetic results of this procedure make it ideal for patients who have esthetic concerns regarding particular difficulties with healing; however, in common with all new surgical procedures, further evidence must be sought to confirm its indications over time.
doi:10.1159/000350854
PMCID: PMC3821510  PMID: 24783047
Thyroid disease; Transaxillary robotic thyroid surgery; Cosmesis

4.  Results of combined treatment of anaplastic thyroid carcinoma (ATC) 
BMC Cancer  2011;11:469.
Background
Anaplastic thyroid carcinoma (ATC) is among the most aggressive human malignancies. It is associated with a high rate of local recurrence and with poor prognosis.
Methods
We retrospectively reviewed 44 consecutive patients treated between 1996 and 2010 at Leon Berard Cancer Centre, Lyon, France. The combined treatment strategy derived from the one developed at the Institut Gustave Roussy included total thyroidectomy and cervical lymph-node dissection, when feasible, combined with 2 cycles of doxorubicin (60 mg/m2) and cisplatin (100 mg/m2) Q3W, hyperfractionated (1.2 Gy twice daily) radiation to the neck and upper mediastinum (46-50 Gy), and then four cycles of doxorubicin-cisplatin.
Results
Thirty-five patients received the three-phase combined treatment. Complete response after treatment was achieved in 14/44 patients (31.8%). Eight patients had a partial response (18.2%). Twenty-two (50%) had progressive disease. All patients with metastases at diagnosis died shortly afterwards. Thirteen patients are still alive. The median survival of the entire population was 8 months.
Conclusion
Despite the ultimately dismal prognosis of ATC, multimodality treatment significantly improves local control and appears to afford long-term survival in some patients. There is active ongoing research, and results obtained with new targeted systemic treatment appear encouraging.
doi:10.1186/1471-2407-11-469
PMCID: PMC3219746  PMID: 22044775
5.  Anaplastic Thyroid Carcinoma Following Radioactive Iodine Therapy for Graves' Disease 
Endocrinology and Metabolism  2013;28(1):61-64.
Radioactive iodine (RAI) therapy has been used as a treatment option for Graves' disease, and it has been widely accepted to be safe. On the other hand, some evidence suggests that RAI therapy is possibly associated with a small increased risk of thyroid cancer. Herein, we report a rare case of anaplastic thyroid carcinoma (ATC) associated with Graves' disease, following RAI treatment. A 42-year-old woman had been diagnosed with Graves' disease and although she was treated with an antithyroid drug, she remained in a hyperthyroid state, which led to two RAI treatments. More than 10 years later, the patient revisited our clinic due to hoarseness, dysphagia, and dyspnea, which had lasted for 2 months. Neck computed tomography suggested thyroid carcinoma and a lymph node biopsy showed metastatic papillary carcinoma. The patient underwent total thyroidectomy and was finally diagnosed as having an ATC. It is not clear if the occurrence of ATC reported here was influenced by the RAI therapy or alternatively, it may only represent the delayed recognition of a rare change in the natural history of Graves' disease. Nevertheless, this report is worthwhile since it presents a very rare case of ATC that occurred eleven years after the RAI therapy for Graves' disease.
doi:10.3803/EnM.2013.28.1.61
PMCID: PMC3811800  PMID: 24396653
Thyroid cancer, anaplastic; Graves disease; Radioactive iodine therapy
6.  Anaplastic thyroid carcinoma: A comprehensive review of current and future therapeutic options 
Anaplastic thyroid carcinoma (ATC) is the rarest, but deadliest histologic type among thyroid malignancies, with a dismal median survival of 3-9 mo. Even though ATC accounts for less than 2% of all thyroid tumors, it is responsible for 14%-39% of thyroid carcinoma-related deaths. ATC clinically presents as a rapidly growing mass in the neck, associated with dyspnoea, dysphagia and vocal cord paralysis. It is usually locally advanced and often metastatic at initial presentation. For operable diseases, the combination of radical surgery with adjuvant radiotherapy or chemotherapy, using agents such as doxorubicin and cisplatin, is the best treatment strategy. Cytotoxic drugs for advanced/metastatic ATC are poorly effective. On the other hand, targeted agents might represent a viable therapeutic option. Axitinib, combretastatin A4, sorafenib and imatinib have been tested in small clinical trials of ATC, with a promising disease control rate ranging from 33% to 75%. Other clinical trials of targeted therapy for thyroid carcinoma are currently ongoing. Biological agents that are under investigation include pazopanib, gefitinib and everolimus. With the very limited therapeutic armamentarium available at the present time, targeted therapy constitutes an exciting new horizon for ATC. In future, biological agents will probably represent the standard of care for this aggressive malignancy, in the same fashion as it has recently occurred for other chemo-refractory tumors, such as kidney and hepatic cancer.
doi:10.5306/wjco.v2.i3.150
PMCID: PMC3100480  PMID: 21611089
Anaplastic thyroid cancer; Targeted agents
7.  Long-term results of radiotherapy in anaplastic thyroid cancer 
Background
Anaplastic thyroid cancer (ATC) is an aggressive malignant tumour with a poor prognosis. The median overall survival is described in the literature to be just 6 months, however, in series of selected patients treated by multimodal therapy cases of long-time-survival have been reported. We analyzed the role of radiotherapy and the impact of other therapies and clinical features on survival in patients with ATC.
Methods
In a retrospective analysis of all patients (n = 40), who presented with histologically proven ATC at a single centre between 1989 and 2008, patient and treatment characteristics with a focus on details of radiotherapy were registered and the survival status determined.
Results
39 of 40 patients received radiotherapy, 80% underwent surgery and 15% had chemotherapy. The median dosis of radiation was 50 Gy (6–60.4 Gy), in 87.5% fractionation was once daily. In 49.4% opposing-field techniques were applied, in 14% 3D-conformal-techniques and 32.5% combinations of both.
The median overall survival (OS) was 5 months, 1-year survival 35.2% and 5-year-survival 21.6%. Interestingly, 24.3% survived 2 years or longer. Three factors could be identified as predictors of improved overall survival: absence of lymph node metastasis (N0) (median OS 18.3 months), median dose of radiation of 50 Gy or more (median OS 10.5 months) and the use of any surgery (median OS 10.5 months).
Conclusions
Despite the generally poor outcome, the combination of surgery and intensive radiotherapy can result in long-term survival in selected patients with ATC.
doi:10.1186/1748-717X-9-90
PMCID: PMC3994242  PMID: 24685141
Anaplastic thyroid cancer (ATC); Undifferentiated thyroid cancer (UTC); Radiotherapy; Multimodal therapy; Prognostic factors; Long-term survival
8.  Anaplastic Thyroid Carcinoma 
Thyroid cancers represent about 1% of all human cancers. Differentiate thyroid carcinomas (DTCs), papillary and follicular cancers, are the most frequent forms, instead Anaplastic Thyroid Carcinoma (ATC) is estimated to comprise 1–2% of thyroid malignancies and it accounts for 14–39% of thyroid cancer deaths. The annual incidence of ATC is about one to two cases/million, with the overall incidence being higher in Europe (and area of endemic goiter) than in USA. ATC has a more complex genotype than DTCs, with chromosomal aberrations present in 85–100% of cases. A small number of gene mutations have been identified, and there appears to be a progression in mutations acquired during dedifferentiation. The mean survival time is around 6 months from diagnosis an outcome that is frequently not altered by treatment. ATC presents with a rapidly growing fixed and hard neck mass, often metastatic local lymph nodes appreciable on examination and/or vocal paralysis. Symptoms may reflect rapid growth of tumor with local invasion and/or compression. The majority of patients with ATC die from aggressive local regional disease, primarily from upper airway respiratory failure. For this reason, aggressive local therapy is indicated in all patients who can tolerate it. Although rarely possible, complete surgical resection gives the best chance of long-term control and improved survival. Therapy options include surgery, external beam radiation therapy, tracheostomy, chemotherapy, and investigational clinical trials. Multimodal or combination therapy should be useful. In fact, surgical debulking of local tumor, combined with external beam radiation therapy and chemotherapy as neoadjuvant (before surgery) or adjuvant (after surgery) therapy, may prevent death from local airway obstruction and as best may slight prolong survival. Investigational clinical trials in phase I or in phase II are actually in running and they include anti-angiogenetic drugs, multi-kinase inhibitor drugs.
doi:10.3389/fendo.2012.00084
PMCID: PMC3389605  PMID: 22783225
anaplastic; cancer; genetic alteration; prognosis; therapy; thyroid; treatment; tumor
9.  Genetic mutations in the treatment of anaplastic thyroid cancer: a systematic review 
BMC Surgery  2013;13(Suppl 2):S44.
Background
Anaplastic thyroid cancer (ATC) is a rare, lethal disease associated with a median survival of 6 months despite the best multidisciplinary care. Surgical resection is not curative in ATC patients, being often a palliative procedure. Multidisciplinary care may include surgery, loco-regional radiotherapy, and systemic therapy. Besides conventional chemotherapy, multi kinase-targeted inhibitors are emerging as novel therapeutic tools. The numerous molecular alteration detected in ATC are targets for these inhibitors. The aim of this review is to determine the prevalence of the major genetic alterations occurring in ATC and place the results in the context of the emerging kinase-targeted therapies.
Methods
The study is based on published PubMed studies addressing the prevalence of BRAF, RAS, PTEN, PI3KCA and TP53 mutations and RET rearrangements in ATC.
Results
21 articles dealing with 652 genetic analyses of the selected genes were used. The overall prevalence determined were the following: RET/PTC, 4%; BRAF, 23%; RAS, 60%; PTEN, 16%; PI3KCA, 24%; TP53, 48%. Genetic alterations are sometimes overlapping.
Conclusions
Mutations of BRAF, PTEN and PI3KCA genes are common in ATC, with RAS and TP53 being the most frequent. Given ATC genetic complexity, effective therapies may benefit from individualized therapeutic regimens in a multidisciplinary approach.
doi:10.1186/1471-2482-13-S2-S44
PMCID: PMC3851243  PMID: 24267151
10.  Anaplastic Thyroid Cancer: Ultrasonographic Findings and the Role of Ultrasonography-Guided Fine Needle Aspiration Biopsy 
Yonsei Medical Journal  2013;54(6):1400-1406.
Purpose
To investigate the ultrasonographic (US) features of anaplastic thyroid cancer (ATC) and the diagnostic performance of US-guided fine needle aspiration biopsy (FNAB) therein.
Materials and Methods
Eighteen cases of ATC diagnosed between January 2001 and May 2011 were included. FNAB was performed in all cases. Initial FNAB results were divided into three groups: 1) the cytological ATC group, cytological diagnosis of ATC; 2) the underestimated group, cytological diagnoses of malignancy other than ATC; and 3) the false negative group, cytological diagnoses of atypical, benign and non-diagnostic lesions. We retrospectively reviewed US findings and compared treatment modalities between each group.
Results
Among the 18 patients, there were nine in the initially cytological ATC group, four in the underestimated group and five in the false negative group. The most common US features of ATC were a solid (64.7%) and irregular shaped (88.2%) mass with lymph node involvement (76.4%). However, except for lymph node involvement (p=0.003), US findings for each group were not statistically different. The initial cytological diagnostic accuracy of ATC was 50% (9/18). Surgery was performed less in the ATC group (11%) and the false negative group (20%) than the underestimated group (75%).
Conclusion
The US features of ATC were not especially different from other types of aggressive thyroid cancer. A correct diagnosis of ATC by initial US-FNAB was made in 50% of the patients, which is significant in that therapeutic surgery can be undertaken in lower numbers if correctly diagnosed.
doi:10.3349/ymj.2013.54.6.1400
PMCID: PMC3809886  PMID: 24142644
Anaplastic thyroid cancer; fine needle aspiration biopsy; ultrasonography
11.  Predictors of thyroid tumor aggressiveness. 
Western Journal of Medicine  1996;165(3):131-138.
Thyroid cancers are classified as papillary, follicular (including Hürthle cell), medullary, and anaplastic. Papillary cancers account for about 82% of all thyroid cancers, follicular about 8%, medullary about 6%, Hürthle cell 3%, and anaplastic 1%. The prognosis of patients with papillary thyroid cancer is usually favorable, whereas most patients with anaplastic cancer die within 6 months. The behavior of papillary thyroid cancer can be predicted by patient age, sex, tumor size, local invasion, angioinvasion, lymph node metastases, distant metastases, as well as tumor differentiation and ability to take up radioactive iodine. Thus, older male patients with larger or invasive tumors, with angioinvasion, lymph node or distant metastases, and with tumors that do not take up radioactive iodine or cannot be completely surgically resected have a worse prognosis. Anaploid tumors, tumors with a low adenylate cyclase response to thyroid-stimulating hormone tumors, tumors that are ras-and gsp-positive, and tumors that are p21-positive and p53-positive also appear to behave in a more aggressive manner. In contrast, lymphocytic thyroiditis associated with papillary thyroid cancer predicts fewer recurrences and an improved survival. The treatment of patients with papillary thyroid cancer is controversial primarily because most patients do well with relatively minimal therapy, and there are no prospective studies concerning the merits of various treatments. Much of the controversy relates to the safety of thyroidectomy versus other procedures and, to a lesser extent, when to do a central or modified radical neck dissection. The rate of recurrence is lower, and the death rate may also be lower when patients are treated initially by total thyroidectomy. The rationale for total thyroidectomy is that it enables one to use radioactive iodine to detect and treat local and distant metastases, and it makes serum thyroglobulin determination more sensitive for detecting persistent disease. Total thyroidectomy should be associated with a permanent complication rate of less than 2%. Thyroid-stimulating hormone suppression therapy is recommended by most experts for patients with differentiated thyroid cancer and supported by most clinical and laboratory studies. Central and lateral node selection is recommended for patients with palpable lymphadenopathy.
Images
PMCID: PMC1303719  PMID: 8909165
12.  Alternative surgical strategies in patients with sporadic medullary thyroid carcinoma: Long-term follow-up 
Oncology Letters  2011;2(5):975-980.
The extent of surgical resection in patients with sporadic medullary thyroid carcinoma (SMTC) remains controversial. The aim of the present study was to discuss the prognosis of sporadic medullary thyroid carcinoma with different surgical treatments. Of 73 patients with SMTC (mean age of 43.78 years at diagnosis), 70 patients were followed up for 12.0-169.0 months (median 90.0). Having given their informed consent, 12 patients underwent total thyroidectomy with bilateral central neck dissection (group A), 40 underwent subtotal thyroidectomy preserving contralateral thyroid tissue on the entrance point of the recurrent laryngeal nerve into the larynx with ipsilateral modified radical neck dissection (group B), and 18 patients underwent subtotal thyroidectomy preserving contralateral thyroid tissue on the entrance point of the recurrent laryngeal nerve into the larynx with bilateral modified radical neck dissection (group C). The diagnosis was confirmed by a pathology examination. The incidences of hypoparathyroidism and recurrent laryngeal nerve injury, the cancer recurrence rates and survival time were investigated post-operatively. Significant differences were found between groups A, B and C in the incidence of hypoparathyroidism (χ2=40.9, P<0.01), as well as that of recurrent laryngeal nerve injury (χ2=32.9, P<0.01). The cancer recurrence rates in groups A, B and C were 75.0% (9/12), 2.5% (1/40) and 44.4% (8/18) respectively, (χ2=31.1, P<0.01) and the cure rates were 25, 97.5 and 55.6% respectively (χ2=31.1, P<0.01). The mean survival times in groups A, B and C were 77.8, 106.1 and 111.0 months respectively, but significant difference was noted (χ2=3.2, P>0.05). In conclusion, compared to total thyroidectomy with bilateral central neck dissection, subtotal thyroidectomy with ipsilateral/bilateral modified radical neck dissection showed a lower incidence of hypoparathyroidism, recurrent laryngeal nerve injury and lower rates of recurrence, along with a similar cumulative survival.
doi:10.3892/ol.2011.344
PMCID: PMC3408028  PMID: 22866159
13.  Outcome after intensity modulated radiotherapy for anaplastic thyroid carcinoma 
BMC Cancer  2014;14:235.
Background
Anaplastic thyroid carcinoma (ATC) is a malignancy with one of the highest fatality rates. We reviewed our recent clinical experience with intensity modulated radiotherapy (IMRT) combined with surgery and chemotherapy for the management of ATC.
Methods
13 patients with ATC who were treated by IMRT in our institution between October 2008 and February 2011, have been analyzed. The target volume for IMRT was planned to include Gross tumor volume (GTV): primary tumor plus any N + disease (66 Gy/33 F/6.6 W), with elective irradiation of thyroid bed, bilateral level II through VI and mediastinal lymph nodes to the level of the carina (54-60 Gy). Seven patients received surgical intervention and eleven patients had chemotherapy.
Results
The median radiotherapy dose to GTV was 60 Gy/30 fractions/6 weeks. The median survival time of the 13 patients was 9 months. The direct causes of death were distant metastases (75%) and progression of the locoregional disease (25%). Ten patients were spared dyspnea and tracheostomy because their primary neck lesion did not progress.
Conclusion
The results showed that IMRT combined by surgery and chemotherapy for ATC might be beneficial to improve locoregional control. Further new therapies are needed to control metastases.
doi:10.1186/1471-2407-14-235
PMCID: PMC3976675  PMID: 24690325
Anaplastic thyroid carcinoma; ATC; Intensity modulated radiotherapy; Locoregional control; Distant metastases
14.  Thyroid Function after Subtotal Thyroidectomy in Patients with Graves' Hyperthyroidism 
The Scientific World Journal  2012;2012:548796.
Background. Subtotal thyroidectomy is a surgical procedure, in which the surgeon leaves a small thyroid remnant in situ to preserve thyroid function, thereby preventing lifelong thyroid hormone supplementation therapy. Aim. To evaluate thyroid function after subtotal thyroidectomy for Graves' hyperthyroidism. Subjects and Methods. We retrospectively reviewed the medical records of all patients (n = 62) who underwent subtotal thyroidectomy for recurrent Graves' hyperthyroidism between 1992 and 2008 in our hospital. Thyroid function was defined according to plasma TSH and free T4 values. Results. Median followup after operation was 54.6 months (range 2.1–204.2 months). Only 6% of patients were euthyroid after surgery. The majority of patients (84%) became hypothyroid, whereas 10% of patients had persistent or recurrent hyperthyroidism. Permanent recurrent laryngeal nerve palsy and permanent hypocalcaemia were noted in 1.6% and 3.2% of patients, respectively. Conclusion. In our series, subtotal thyroidectomy for Graves' hyperthyroidism was associated with a high risk of postoperative hypothyroidism and a smaller, but significant, risk of persistent hyperthyroidism. Our data suggest that subtotal thyroidectomy seems to provide very little advantage over total thyroidectomy in terms of postoperative thyroid function.
doi:10.1100/2012/548796
PMCID: PMC3290451  PMID: 22448136
15.  Endoscopic thyroidectomy: Our technique 
Minimally invasive surgery is widely employed for the treatment of thyroid diseases. Several minimal access approaches to the thyroid gland have been described. The commonly performed surgeries have been endoscopic lobectomies. We have performed endoscopic total thyroidectomy by the anterior chest wall approach. In this study, we have described our technique and evaluated the feasibility and efficacy of this procedure.
Materials and Methods:
From June 2005 to August 2006, 15 cases of endoscopic thyroidectomy were done at our institute. Five patients were male and 10 were female. Mean age was 45 years. (Range 23 to 71 years). Four patients had multinodular goiter and underwent near-total thyroidectomy; four patients had follicular adenoma and underwent hemithyroidectomy. Out of the seven patients of papillary carcinoma, four were low-risk and so a hemithyroidectomy was performed while three patients in the high risk group underwent total thyroidectomy. A detailed description of the surgical technique is provided.
Results:
The mean nodule size was 48 mm (range 20-80 mm) and the mean operating time was 85 min (range 60-120 min). In all cases, the recurrent laryngeal nerve was identified and preserved intact, the superior and inferior parathyroids were also identified in all patients. No patients required conversion to an open cervicotomy. All patients were discharged the day after surgery. All thyroidectomies were completed successfully. No recurrent laryngeal nerve palsies or postoperative tetany occurred. The postoperative course was significantly less painful and all patients were satisfied with the cosmetic results.
Conclusions:
It is possible to remove large nodules and perform as well as total thyroidectomies using our endoscopic approach. It is a safe and effective technique in the hands of an appropriately trained surgeon. The patients get a cosmetic benefit without any morbidity.
doi:10.4103/0972-9941.37191
PMCID: PMC2749190  PMID: 19789664
Endoscopy; technique; thyroidectomy
16.  Total Thyroidectomy: a safe and effective treatment for Graves' disease 
Background
Thyroidectomy as a first line treatment for Graves’ disease is rarely utilized in the US. The purpose of this study was to analyze the safety and efficacy of thyroid surgery among patients with Graves’ disease.
Methods
56 patients with Graves’ disease underwent thyroid surgery between 05/1994 and 05/2008 at a single academic institution. Pre-operative, intra-operative, and post-operative variables were analyzed.
Results
A total of 58 surgeries were performed: 55.1% (n=32) total thyroidectomy, 41.3% (n=24) subtotal/lobectomy, 3.4 % (n=2) completion thyroidectomy. The average gland weight was 47.3 ± 10.8 gm, with 70% weighing > 30 gm. Reasons for having thyroid surgery were persistent disease despite medical therapy (46.6%), patient preference (24.1%), multinodular goiter/cold nodules (20.3%), failed RAI (radioactive iodine) treatment (16%), and opthalmopathy (12.1%). Of those patients that failed prior RAI therapy, the only factor that was predictive of failure was disease severity, as demonstrated by a markedly elevated initial free-T4 value (11.8 ± 4.5 ng/dL, p=0.04). Transient symptomatic hypocalcemia occurred in 10.7% (n=6) of patients, and 1 patient (1.8%) had symptomatic hypocalcemia lasting > 6 months. There were no permanent recurrent laryngeal nerve injuries. There was no difference in overall complication rates between patients based on surgical procedure (subtotal vs. total thyroidectomy), preoperative RAI treatment, or gland size. Recurrences occurred in 6% of the subtotal thyroidectomy group and 0% of the total thyroidectomy group (p=0.008).
Conclusion
Thyroidectomy for patients with Graves’ disease can be performed with very low complication rates and when a total thyroidectomy is performed there is almost no risk of recurrence.
doi:10.1016/j.jss.2010.12.038
PMCID: PMC3085652  PMID: 21345453
17.  Single-Incision Transaxillary Robotic Thyroidectomy: Challenges and Limitations in a North American Population 
Objective
We reviewed our initial experience with robotic thyroidectomy to identify challenges and limitations of this new surgical approach when applied to a North American population.
Study Design
Case series.
Setting
Academic institution.
Subjects/Methods
Retrospective review of 18 consecutive robotic thyroid lobectomies performed from February 2010 to April 2012 involving 16 female patients. Two patients underwent robot-assisted completion thyroidectomy a few months following the initial thyroid surgery, one for cancer and the other for goiter.
Results
Median age was 47.5 years (range, 18–62 years), and median body mass index was 28.7 (range, 19.4–44.5). Median thyroid nodule size was 2.9 cm (range, 1.1–4.7 cm). All but 1 case (6%) was performed successfully via single axillary incision. There was no conversion to an open approach. Median operative time was 170 minutes (range, 95–220 minutes), and median blood loss was 12.5 mL (range, 5–75 mL). Complications occurred in 4 cases (22%) to include temporary vocal cord pareses (n = 3) and a postoperative hematoma that required exploration. Median hospital stay was 2 days (range, 1–3 days).
Conclusion
Single-incision transaxillary robotic thyroidectomy can be technically challenging in North American patients with a larger body frame due to difficulty in optimal placement of all 4 robotic instruments via a single axillary incision. All 3 cases of temporary vocal cord paresis occurred early in our experience and may have been due to our relative inexperience with this new approach and associated instrumentation. Other limitations include less than optimal visualization of the recurrent laryngeal nerve in the contralateral lobe as well as poor access to the substernal region.
Level of Evidence
4
doi:10.1177/0194599812461610
PMCID: PMC3902132  PMID: 23008331
thyroid surgery; robotic thyroidectomy; transaxillary; thyroid
18.  Role of prophylactic central neck dissection in cN0 papillary thyroid cancer 
Summary
Prophylactic central neck dissection in papillary thyroid cancer is controversial. In this retrospective cohort study, the aim was to assess possible advantages of prophylactic central neck dissection with total thyroidectomy in cN0 papillary thyroid cancer. A total of 244 consecutive patients with papillary thyroid cancer, without clinical and ultrasound nodal metastases (cN0), were evaluated out of 1373 patients operated for a thyroid disease at the Istituto Europeo di Oncologia, Milan, Italy from 1994 to 2006. Of these 244 patients, 126 (Group A) underwent thyroidectomy with central neck dissection, while 118 (Group B) underwent thyroidectomy alone. Demographic, clinical and pathological features were analysed. Overall recurrence rate was 6.3% (8/126) in Group A and 7.7% (9/118) in Group B, with a mean follow-up of 47 (Group A) and 64 (Group B) months. In Group A patients, 47% were pN1a and all patients with recurrence had nodal involvement (p = 0.002). Survival rate did not differ in the two groups. Nine patients were lost to follow-up. Group A patients were older and their tumours were larger in size; according to the pT distribution, a higher extra-capsular invasion rate was observed. The two groups were equivalent as far as concerns histological high risk variants and multifocality. Nodal metastases correlated with stage: pT1-2 vs. pT3-T4a, p = 0.0036. A lower risk of nodal metastases was related to thyroiditis (p = 0.0034). In conclusion, central neck metastases were predictive of recurrence without influencing prognosis. From data obtained, possible greatest efficacy of central neck dissection in pT3-4 papillary thyroid cancer without thyroiditis is suggested.
PMCID: PMC2808683  PMID: 20111614
Thyroid; Papillary thyroid cancer; Nodal metastases; Central neck dissection
19.  Video-assisted thyroidectomy: lessons learned after more than one decade 
Summary
In selected patients, video-assisted thyroidectomy can be considered a safe and validated procedure offering significant advantages over conventional surgery, with no additional morbidity. Aim of this study was to evaluate the results obtained in a series of patients selected for video-assisted thyroidectomy over a 10-years period. All patients who underwent video-assisted thyroidectomy from June 1998 to June 2009 were considered. The eligibility criteria for video-assisted thyroidectomy are: thyroid nodules ≤ 35 mm; estimated thyroid volume < 30 ml; no previous conventional neck surgery and/or radiation therapy; small, low-risk papillary thyroid carcinoma. A total of 1363 video-assisted thyroidectomies were attempted in the time period considered. Conversion to the conventional procedure was necessary in 7 cases. Thyroid lobectomy was successfully performed in 157 cases, total thyroidectomy in 1175, and completion thyroidectomy in 24. In 126 patients, the central neck nodes were removed through the same access. Simultaneous video-assisted parathyroidectomy, for a parathyroid adenoma, was performed in 42 patients. Pathological studies showed benign disease in 986 cases, papillary thyroid carcinoma in 368 cases, C-cells hyperplasia in 1 case, and medullary microcarcinoma in 1 patients with RET germline mutation. Post-operative complications included 27 transient and 1 definitive recurrent laryngeal nerve palsy, 230 transient hypocalcemia, 10 definitive hypoparathyroidism, 4 postoperative hematoma and 5 wound infection.
PMCID: PMC2868209  PMID: 20463836
Thyroidectomy; Minimally invasive thyroidectomy; Endoscopic thyroidectomy
20.  Anaplastic Thyroid Carcinoma: A Therapeutic Dilemma 
Yonsei Medical Journal  2005;46(6):759-764.
Anaplastic thyroid carcinoma (ATC) is one of the most malignant human neoplasms and has a grave prognosis. This study gives an update on our experience with this unusual neoplasm, with specific focus on the response to various treatment modalities. Forty-seven patients with histologically proven ATCs were enrolled (19 men, 28 women; mean age, 62.8 years). This number represents 1.5% among a total of 3,088 thyroid cancers treated between 1977 and 2002. The mean tumor diameter was 8.8 cm, and 22 patients had distant metastasis. Extrathyroidal extension was seen in 26 (89.7%) of the cases that underwent surgery. Treatment modalities adopted could be classified into 5 groups: Group 1, biopsy only; Group 2, biopsy and chemoradiotherapy; Group 3, debulking only; Goup 4, debulking and chemoradiotherapy; Group 5, complete excision and chemoradiotherapy. Survival was calculated from the time of diagnosis, and comparisons of survival were done by log-rank analysis. The mean survival was 4.3 months (range, 1.0-21 months). The mean survival based on treatment modalities were as follows: Group 1 (n = 10), 2.1 months, Group 2 (n = 8); 3.6 months; Group 3 (n = 7), 3.0 months; Group 4 (n = 14), 3.5 months, Group 5 (n = 8), 9.4 months. There was no significant difference in survival time between the various types of treatment modalities. Even though a small improvement in survival was observed with complete excision and aggressive multimodality therapy, nearly all ATCs remain unresponsive to ongoing treatment modalities and as such, present a therapeutic dilemma. A more effective treatment regimen should be sought in order to improve survival.
doi:10.3349/ymj.2005.46.6.759
PMCID: PMC2810588  PMID: 16385650
Anaplastic thyroid cancer; treatment modalities; treatment outcome
21.  Total Thyroidectomy in the Mouse: the Feasibility Study in the Non-thyroidal Tumor Model Expressing Human Sodium/Iodide Symporter Gene 
Purpose
This study sought to probe the feasibility of performing total thyroidectomy in the mouse using a non-thyroidal hNIS expressing tumor model.
Materials and Methods
Our thyroidectomy protocol included thorough excision of both lobes and the isthmus. For evaluating the completeness of thyroidectomy, we compared the 99mTc-pertechnetate scans taken before and after thyroidectomy. The prostate cancer cell line was subcutaneously inoculated 2 weeks after the thyroidectomy. When the tumor reached 5-10 mm in diameter, Ad5/35-E4PSESE1a-hNIS was injected intratumorally, and 131I scans were performed. The radioiodine uptakes of the neck and the tumor were compared with those of the other regions.
Results
Total thyroidectomy was performed in 13 mice. Although 38.5% died during or just after thyroidectomy, the others survived in good health for 2 months. Thyroid tissue was completely eliminated using our protocol; the residual uptake of 99mTc-pertechnetate was minimal in the neck area. The neck/background uptake ratio after thyroidectomy was significantly lower than that before thyroidectomy (p < 0.05). Non-thyroidal tumor models were successfully established in all the surviving mice. Radioiodine accumulation in the tumors was visualized on 131I scans, and the neck uptakes were minimal.
Conclusion
Using our total thyroidectomy protocol, we successfully established a hNIS-transfected prostate cancer model with a minimal accumulation of radioiodine in the neck. The relatively high mortality after surgery can be a problem, and this might be reduced by minimizing the surgical stress.
doi:10.1007/s13139-011-0076-x
PMCID: PMC4043020  PMID: 24899988
Mouse; Total thyroidectomy; Surgical technique; Human sodium/iodide symporter
22.  Endoscopic Total Thyroidectomy 
Endoscopic transaxillary total thyroidectomy (ETTT) was found to be a safe and feasible alternative to open thyroidectomy.
Background and Objective:
Endoscopic neck surgery for the thyroid and parathyroid is being tested as an alternative to open thyroidectomy. The aim of this study was to determine the safety and feasibility of endoscopic transaxillary total thyroidectomy (ETTT).
Methods and Results:
Twenty-two consecutive patients from January 2006 to September 2008 underwent ETTT. No conversions to open were necessary. Mean age was 49.3±12.9 years, 20 were female, and 2 were male. Mean operating time was 238 minutes±72.7. Mean blood loss was 40mL±28.3mL. Mean weight of the gland was 137.05g±129.21g. The recurrent laryngeal nerve was identified with no permanent injury. Six patients developed hoarseness of the voice for a mean of 15.1±8.01 days. No patient developed tetany or hypocalcemia requiring treatment. Six patients experienced transient numbness in the anterior chest wall lasting 2 weeks in 5 patients and 2 months in one. All patients were discharged within 24 hours of admission.
Conclusion:
ETTT requires additional operative time compared with the open approach, but is cosmetically favorable. Visualization of the nerve and parathyroid is much better. Although the learning curve is steep, with experience the operative time will decrease. ETTT is different but safe and feasible.
doi:10.4293/108680809X12589998404209
PMCID: PMC3030786  PMID: 20202393
Minimal; Invasive; Endoscopic; Thyroidectomy; Transaxillary
23.  Papillary carcinoma arising from thyroglossal duct cyst with thyroid and lateral neck metastasis 
INTRODUCTION
Thyroglossal duct carcinomas (TGDC) are rare, with approximately 274 reported cases since the first report in 1915. The prevalence of carcinomas in surgically removed thyroglossal duct cyst (TGD) is less than 1%. The usual recommended treatment for this condition is the Sistrunk operation, but controversies remain regarding the need for total or partial thyroidectomy.
PRESENTATION OF CASE
A 28-year-old woman was admitted to our hospital with the symptoms of painless midline neck swelling and growing mass. A preoperative computed tomography (CT) showed a 4 cm sized heterogeneous mass at the infrahyoid anterior neck. Ultrasonography of the neck additionally showed suspicious metastatic lymph node at right level VI, both level VI. The patient underwent a Sistrunk operation. The frozen section revealed papillary carcinoma arising from TGDC and also revealed metastatic papillary carcinoma in the right thyroid, at right level III and level VI. Total thyroidectomy, right modified radical neck dissection and central neck dissection were performed. The thyroid gland and TGD were confirmed papillary carcinoma. The dissected neck lymph nodes revealed metastatic papillary carcinoma.
DISCUSSION
The usual recommended treatment for TGD is the Sistrunk procedure. There is controversy regarding whether total or partial thyroidectomy should be performed.
CONCLUSION
Physicians should be aware of extended operation, including thyroidectomy and/or neck node dissection for TGDC with metastatic lesion of thyroid and neck node.
doi:10.1016/j.ijscr.2013.05.007
PMCID: PMC3710902  PMID: 23807380
Thyroglossal duct carcinoma; Papillary carcinoma; Lateral neck dissection; Sistrunk procedure
24.  Clinicopathologic Features and Treatment Outcomes in Differentiated Thyroid Carcinoma Patients with Concurrent Graves' Disease 
Journal of Korean Medical Science  2008;23(5):796-801.
The clinical behaviors and treatment outcomes of thyroid carcinomas in patients with Graves' disease is a matter of controversy. This study aimed to identify the clinicopathologic features, treatment outcome, and the indicators for predicting recurrence, and to suggest the optimal extent of surgery in these patients. We retrospectively analyzed data of 58 patients who underwent surgical treatment for differentiated thyroid cancer and concurrent Graves' disease. The follow-up period ranged from 23 to 260 months (mean±standard devuation, 116.8±54.0). In our series, the mean age was 40.8±12.7 yr (range, 15-70), with a male-to-female ratio of 1:6.25. The mean tumor size was 13±9 mm (range, 3-62). The surgical methods included 19 cases of total thyroidectomy, 38 cases of subtotal thyroidectomy, and 1 case of completion total thyroidectomy. Locoregional recurrence occurred in four patients (6.9%). The 10-yr overall survival and disease-free survival of patients were 95.8% and 91.1%, respectively. Age over 45 yr (p=0.031), tumor size over 10 mm (p=0.049), multiplicity (p=0.007), extracapsular invasion (p=0.021), and clinical cancer (p=0.035) were significantly more prevalent in patients with locoregional recurrence than in those without recurrence. We recommend that Graves' disease patients should undergo regular ultrasonography screening for early detection of thyroid carcinoma. We also suggest that the choice of extent of surgery should depend on the diagnostic timing (clinical or incidental) and factors for predicting recurrence.
doi:10.3346/jkms.2008.23.5.796
PMCID: PMC2579995  PMID: 18955784
Graves Disease; Differentiated Thyroid Cancer; Incidental Carcinoma; Clinical Carcinoma; Extent of Surgery
25.  A Phase II Trial of Fosbretabulin in Advanced Anaplastic Thyroid Carcinoma and Correlation of Baseline Serum-Soluble Intracellular Adhesion Molecule-1 with Outcome 
Thyroid  2009;19(3):233-240.
Background
Fosbretabulin is a novel vascular-disrupting agent that has antitumor activity against anaplastic thyroid cancer (ATC) cell lines, xenografts, and demonstrable efficacy in a phase I trial. This phase II study determined the efficacy and safety of fosbretabulin in patients with advanced ATC and whether fosbretabulin altered the natural history of ATC by virtue of doubling the median survival. A secondary aim evaluated the prognostic value of serum soluble intracellular adhesion molecule-1 (sICAM).
Methods
Twenty-six patients received fosbretabulin 45 mg/m2 as a 10-minute intravenous infusion on days 1, 8, and 15 of a 28-day cycle. sICAM levels were obtained at baseline, over the first two cycles, and end of therapy. Treatment was continued until disease progression.
Results
Fosbretabulin was well tolerated; grade 3 toxicity was observed in nine patients (35%), and grade 4 toxicity in one (4%). QTc prolongation delayed treatment in four causing one to stop treatment. Median survival was 4.7 months with 34% and 23% alive at 6 and 12 months, respectively. Median duration of stable disease in seven patients was 12.3 months (range, 4.4–37.9 months). Baseline serum sICAM levels were measured in 24 patients with a median 253.5 ng/mL. There was a significant difference in event-free survival among tertiles of baseline sICAM levels (p < 0.009).
Conclusions
There were no objective responses seen with single-agent fosbretabulin as administered in this trial, and we did not observe a doubling of survival as our primary endpoint. This is among the largest prospective trials ever conducted for ATC. Fosbretabulin has an acceptable safety profile in patients with advanced ATC, and one-third survived more than 6 months. Despite a small sample size, low baseline sICAM levels were predictive of event-free survival. Further prospective validation of sICAM as a therapeutic biomarker and exploring combination regimens with fosbretabulin are warranted.
doi:10.1089/thy.2008.0321
PMCID: PMC2913806  PMID: 19265494

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